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Sample records for strong anticancer activity

  1. Cyclometalated Ruthenium(II) Anthraquinone Complexes Exhibit Strong Anticancer Activity in Hypoxic Tumor Cells.

    Science.gov (United States)

    Zeng, Leli; Chen, Yu; Huang, Huaiyi; Wang, Jinquan; Zhao, Donglei; Ji, Liangnian; Chao, Hui

    2015-10-19

    Hypoxia is the critical feature of the tumor microenvironment that is known to lead to resistance to many chemotherapeutic drugs. Six novel ruthenium(II) anthraquinone complexes were designed and synthesized; they exhibit similar or superior cytotoxicity compared to cisplatin in hypoxic HeLa, A549, and multidrug-resistant (A549R) tumor cell lines. Their anticancer activities are related to their lipophilicity and cellular uptake; therefore, these physicochemical properties of the complexes can be changed by modifying the ligands to obtain better anticancer candidates. Complex 1, the most potent member of the series, is highly active against hypoxic HeLa cancer cells (IC50 =0.53 μM). This complex likely has 46-fold better activity than cisplatin (IC50 =24.62 μM) in HeLa cells. This complex tends to accumulate in the mitochondria and the nucleus of hypoxic HeLa cells. Further mechanistic studies show that complex 1 induced cell apoptosis during hypoxia through multiple pathways, including those of DNA damage, mitochondrial dysfunction, and the inhibition of DNA replication and HIF-1α expression, making it an outstanding candidate for further in vivo studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Anticancer Activity of Amauroderma rude

    Science.gov (United States)

    Yang, Xiangling; Li, Haoran; Li, Xiang-Min; Pan, Hong-Hui; Cai, Mian-Hua; Zhong, Hua-Mei; Yang, Burton B.

    2013-01-01

    More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities. PMID:23840494

  3. Anticancer activity of Amauroderma rude.

    Directory of Open Access Journals (Sweden)

    Chunwei Jiao

    Full Text Available More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities.

  4. Anticancer and antiproliferative activity of natural brassinosteroids

    Czech Academy of Sciences Publication Activity Database

    Malíková, J.; Swaczynová, Jana; Kolář, Z.; Strnad, Miroslav

    2008-01-01

    Roč. 69, č. 2 (2008), s. 418-426 ISSN 0031-9422 Institutional research plan: CEZ:AV0Z50380511 Keywords : Brassinosteroids * Anticancer activity * Cell cycle Subject RIV: CE - Biochemistry Impact factor: 2.946, year: 2008

  5. Anticancer Activity of Bacterial Proteins and Peptides.

    Science.gov (United States)

    Karpiński, Tomasz M; Adamczak, Artur

    2018-04-30

    Despite much progress in the diagnosis and treatment of cancer, tumour diseases constitute one of the main reasons of deaths worldwide. The side effects of chemotherapy and drug resistance of some cancer types belong to the significant current therapeutic problems. Hence, searching for new anticancer substances and medicines are very important. Among them, bacterial proteins and peptides are a promising group of bioactive compounds and potential anticancer drugs. Some of them, including anticancer antibiotics (actinomycin D, bleomycin, doxorubicin, mitomycin C) and diphtheria toxin, are already used in the cancer treatment, while other substances are in clinical trials (e.g., p28, arginine deiminase ADI) or tested in in vitro research. This review shows the current literature data regarding the anticancer activity of proteins and peptides originated from bacteria: antibiotics, bacteriocins, enzymes, nonribosomal peptides (NRPs), toxins and others such as azurin, p28, Entap and Pep27anal2. The special attention was paid to the still poorly understood active substances obtained from the marine sediment bacteria. In total, 37 chemical compounds or groups of compounds with antitumor properties have been described in the present article.

  6. Anticancer Activity of Metal Complexes: Involvement of Redox Processes

    Science.gov (United States)

    Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

    2012-01-01

    Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

  7. Isocorydine Derivatives and Their Anticancer Activities

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    Mei Zhong

    2014-08-01

    Full Text Available In order to improve the anticancer activity of isocorydine (ICD, ten isocorydine derivatives were prepared through chemical structure modifications, and their in vitro and in vivo activities were experimentally investigated. 8-Amino-isocorydine (8 and 6a,7-dihydrogen-isocorydione (10 could inhibit the growth of human lung (A549, gastric (SGC7901 and liver (HepG2 cancer cell lines in vitro. Isocorydione (2 could inhibit the tumor growth of murine sarcoma S180-bearing mice, and 8-acetamino-isocorydine (11, a pro-drug of 8-amino-isocorydine (8, which is instable in water solution at room temperature, had a good inhibitory effect on murine hepatoma H22-induced tumors. The results suggested that the isocorydine structural modifications at C-8 could significantly improve the biological activity of this alkaloid, indicating its suitability as a lead compound in the development of an effective anticancer agent.

  8. Peptides with Dual Antimicrobial and Anticancer Activities

    Science.gov (United States)

    Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.

    2017-02-01

    In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting towards intracellular targets, which increases their success comparatively to specific one-target drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

  9. MECHANOMAGNETIC REACTOR FOR ACTIVATION OF ANTICANCER DRUGS

    Directory of Open Access Journals (Sweden)

    Orel V. E.

    2014-02-01

    Full Text Available Mechanomagnetochemical activation can increase the concentration of paramagnetic centers (free radicals in the anticancer drug, for example, doxorubicin that enables to influence its magnetic properties under external electromagnetic field and improve its magnetic sensitivity and antitumor activity. The principles of design and operation of mechanomagnetic reactor for implementation of this technology which includes mechanomagnetochemical activation and electromagnetic radiation of the drug are described in the paper. The methods of vibration magnetometry, electron paramagnetic resonance spectroscopy and high-performance liquid chromatography were used for studying of doxorubicin mechanomagnetic activation effects. The studies have shown that a generator of sinusoidal electromagnetic wave, working chambers from caprolactam, fluoroplastic or organic materials with metal inserts and working bodies made from steel or agate depending on the required doxorubicin magnetic properties are expedient to use in the designed mechanomagnic reactor. Under influence of mechanomagnetochemical activation doxorubicin, which is diamagnetic, acquires the properties of paramagnetic without changing g-factors in the spectra of electron paramagnetic resonance. Mechanomagnetochemical activation of doxorubicin satisfies pharmacopoeia condi tions according to the results of liquid chromatography that points on perspective of this method using in technology of tumor therapy with nanosized structures and external electromagnetic radiation.

  10. Prediction of anticancer activity of aliphatic nitrosoureas using ...

    African Journals Online (AJOL)

    Design and development of new anticancer drugs with low toxicity is a very challenging task and computer aided methods are being increasingly used to solve this problem. In this study, we investigated the anticancer activity of aliphatic nitrosoureas using quantum chemical quantitative structure activity relation (QSAR) ...

  11. Synthesis of Chalcones with Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Syam Mohan

    2012-05-01

    Full Text Available Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer and human<strong> strong>normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC50 values were chosen and studied in detail with MCF-7 cells. The compounds <strong>1strong>, <strong>5strong>, <strong>23strong>, and <strong>25strong> were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05. The ROS level showed 1.3-fold increase (p < 0.05 at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.

  12. Antimicrobial and anticancer activities of extracts from Urginea ...

    African Journals Online (AJOL)

    Background: Increasing antibiotic resistance among human pathogenic microorganisms and the failure of conventional cancer therapies attracting great attention among scientists in the field of herbal medicine to develop natural antimicrobial and anticancer drugs. Thus, the antimicrobial and anticancer activities from fruits ...

  13. Anticancer Activity of Sea Cucumber Triterpene Glycosides

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    Dmitry L. Aminin

    2015-03-01

    Full Text Available Triterpene glycosides are characteristic secondary metabolites of sea cucumbers (Holothurioidea, Echinodermata. They have hemolytic, cytotoxic, antifungal, and other biological activities caused by membranotropic action. These natural products suppress the proliferation of various human tumor cell lines in vitro and, more importantly, intraperitoneal administration in rodents of solutions of some sea cucumber triterpene glycosides significantly reduces both tumor burden and metastasis. The anticancer molecular mechanisms include the induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear factors, NF-κB, and up-down regulation of certain cellular receptors and enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor receptor, Akt (protein kinase B, ERK (extracellular signal-regulated kinases, FAK (focal adhesion kinase, MMP-9 (matrix metalloproteinase-9 and others. Administration of some glycosides leads to a reduction of cancer cell adhesion, suppression of cell migration and tube formation in those cells, suppression of angiogenesis, inhibition of cell proliferation, colony formation and tumor invasion. As a result, marked growth inhibition of tumors occurs in vitro and in vivo. Some holothurian triterpene glycosides have the potential to be used as P-gp mediated MDR reversal agents in combined therapy with standard cytostatics.

  14. Anticancer Activity Of Plant Genus Clerodendrum (Lamiaceae: A Review

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    Donald Emilio Kalonio

    2017-12-01

    Full Text Available Plants of the genus Clerodendrum (Lamiaceae is widespread in tropical and subtropical regions. Plants of this genus are used both empirically and scientifically as anti-inflammatory, antidiabetic, antimalarial, antiviral, antihypertensive, hypolipidemic, antioxidant, and antitumor. Results of the molecular docking simulation of chemical content of these plants could potentially provide an anticancer effect. This paper aims to review the anticancer activity of plant genus Clerodendrum based on scientific data. The method used in this study is the literature study. Searches were conducted online (in the database PubMed, Science Direct and Google Scholar and on various books (Farmakope Herbal Indonesia and PROSEA. A total 12 plants of the genus Clerodendrum have anticancer activity in vitro and in vivo, thus potentially to be developed as a source of new active compounds with anticancer activity.

  15. Synthesis, docking and anticancer activity studies of D-proline ...

    Indian Academy of Sciences (India)

    D-proline-incorporated wainunuamide — a cyclic octapeptide was synthesized and characterized ... Cyclic octapeptide; molecular docking; solution phase synthesis; anticancer activity ..... dynamics and their binding affinities, using free energy.

  16. Randomized anticancer and cytotoxicity activities of Guibourtia ...

    African Journals Online (AJOL)

    Materials and Methods: The plants were screened for the presence of coumarins, alkaloids, flavonoids, anthraquinones, steroids and terpenoids using thin layer chromatography. Anticancer screening was performed on a panel of three cancer cell lines, while cytotoxicity was determined using a human fibroblast cell line, ...

  17. Antioxidant and Anticancer Activities of Wampee (Clausena lansium (Lour. Skeels Peel

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    K. Nagendra Prasad

    2009-01-01

    Full Text Available Antioxidant activities of wampee peel extracts using five different solvents (ethanol, hexane, ethyl acetate, butanol and water were determined by using in-vitro antioxidant models including total antioxidant capability, 1,1-diphenyl-2-picryl hydrazyl (DPPH radical scavenging activity, reducing power, and superoxide scavenging activity. Ethyl acetate fraction (EAF exhibited the highest antioxidant activity compared to other fractions, even higher than synthetic antioxidant butylated hydroxyl toluene (BHT. In addition, the EAF exhibited strong anticancer activities against human gastric carcinoma (SGC-7901, human hepatocellular liver carcinoma (HepG-2 and human lung adenocarcinoma (A-549 cancer cell lines, higher than cisplatin, a conventional anticancer drug. The total phenolic content of wampee fraction was positively correlated with the antioxidant activity. This is the first report on the antioxidant and anticancer activities of the wampee peel extract. Thus, wampee peel can be used potentially as a readily accessible source of natural antioxidants and a possible pharmaceutical supplement.

  18. Anticancer Activity of Extracts from some Endemic Tanzanian Plants ...

    African Journals Online (AJOL)

    Of the 52 extracts from 26 plants of different families tested, 5 demonstrated potential activity on the cells. Extract X13 had an exceptionally high activity on both cell lines while extract X29 was highly active on HeLa cells. Fractionation and isolation of constituents from the extracts that have shown anticancer activity in these ...

  19. Anticancer Activity from Active Fraction of Sea Cucumber

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    Nurul Mutia Putram

    2017-05-01

    Full Text Available Sea Cucumber Holothuria atra is one of marine organisms has been used as a new source of novel bioactive compounds. Many of them have been used as the lead compounds in discovery of new anticancer drugs. The objective of this study was to determine the active fractions of sea cucumber (H. atra which have anticancer activity. H. atra was macerated using ethanol and the extract was freezedried using a freeze dryer. The crude extract was partitioned using n-hexane, ethyl acetate, and methanol-water (3:1:1:1. Cytotoxicity test was performed using HeLa (cervic cancer cell line and MCF-7 (breast cancer cell line based on the MTT assay. The crude extract of H. atra showed the best cytotoxic activity against HeLa cells (IC50 = 12.48 µg/mL and MCF-7 cells (IC50 = 17.90 µg/mL. The toxicity tests showed the IC50 value of the n-hexane fraction, ethyl acetate fraction, and methanol-water fraction against HeLa cells HeLa (IC50 = 76.45 µg/mL; 77.95 µg/mL;  14.27 µg/mL and MCF-7 cells (IC50 = 58.50 µg/mL; 59.59 µg/mL; 14.33 µg/mL.

  20. Antithrombotic/anticoagulant and anticancer activities of selected ...

    African Journals Online (AJOL)

    Antithrombotic/anticoagulant and anticancer activities of selected medicinal plants from South Africa. NLA Kee, N Mnonopi, H Davids, RJ Naudé, CL Frost. Abstract. Nine plants available in the Eastern Cape Province of South Africa were tested for antithrombotic and/or anticoagulant activity. Organic (methanol) and aqueous ...

  1. Studies on anticancer activities of lactoferrin and lactoferricin.

    Science.gov (United States)

    Yin, Cui Ming; Wong, Jack Ho; Xia, Jiang; Ng, Tzi Bun

    2013-09-01

    This review mainly summarizes results of recent studies on the anticancer activity of the multifunctional protein lactoferrin (Lf) and its derived peptide lactoferricin (Lfcin). The basic information on Lf and Lfcin, such as their sources, structures, and biological properties which favor their antitumor activity is introduced. The major anticancer mechanisms of Lf and Lfcin including cell cycle arrest, apoptosis, anti-angiogenesis, antimetastasis, immune modulation and necrosis are discussed. Other information from in vivo studies employing a mouse model is also provided. In addition, the roles of talatoferrin and delta lactoferrin, as well as improvement in drug delivery will be covered.

  2. Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives

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    Yang Li

    2016-02-01

    Full Text Available A total of forty novel glycyrrhetinic acid (GA derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231 in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC50 1.88 ± 0.20 and 1.37 ± 0.18 µM for MCF-7 and MDA-MB-231, respectively and merits further exploration as a new anticancer agent.

  3. Anticancer activities of bovine and human lactoferricin-derived peptides.

    Science.gov (United States)

    Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

    2017-02-01

    Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

  4. Enhancement of anticancer activity in antineovascular therapy is based on the intratumoral distribution of the active targeting carrier for anticancer drugs

    International Nuclear Information System (INIS)

    Maeda, Noriyuki; Miyazawa, Souichiro; Shimizu, Kosuke; Asai, Tomohiro; Yonezawa, Sei; Oku, Naoto; Kitazawa, Sadaya; Namba, Yukihiro; Tsukada, Hideo

    2006-01-01

    We previously observed the enhanced anticancer efficacy of anticancer drugs encapsulated in Ala-Pro-Arg-Pro-Gly-polyethyleneglycol-modified liposome (APRPG-PEG-Lip) in tumor-bearing mice, since APRPG peptide was used as an active targeting tool to angiogenic endothelium. This modality, antineovascular therapy (ANET), aims to eradicate tumor cells indirectly through damaging angiogenic vessels. In the present study, we examined the in vivo trafficking of APRPG-PEG-Lip labeled with [2- 18 F]2-fluoro-2-deoxy- D -glucose ([2- 18 F]FDG) by use of positron emission tomography (PET), and observed that the trafficking of this liposome was quite similar to that of non-targeted long-circulating liposome (PEG-Lip). Then, histochemical analysis of intratumoral distribution of both liposomes was performed by use of fluorescence-labeled liposomes. In contrast to in vivo trafficking, intratumoral distribution of both types of liposomes was quite different: APRPG-PEG-Lip was colocalized with angiogenic endothelial cells that were immunohistochemically stained for CD31, although PEG-Lip was localized around the angiogenic vessels. These results strongly suggest that intratumoral distribution of drug carrier is much more important for therapeutic efficacy than the total accumulation of the anticancer drug in the tumor, and that active delivery of anticancer drugs to angiogenic vessels is useful for cancer treatment. (author)

  5. Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves

    Science.gov (United States)

    Ganogpichayagrai, Aunyachulee; Palanuvej, Chanida; Ruangrungsi, Nijsiri

    2017-01-01

    Diabetes and cancer are a major global public health problem. Plant-derived agents with undesirable side-effects were required. This study aimed to evaluate antidiabetic and anticancer activities of the ethanolic leaf extract of Mangifera indica cv. Okrong and its active phytochemical compound, mangiferin. Antidiabetic activities against yeast α-glucosidase and rat intestinal α-glucosidase were determined using 1 mM of p-nitro phenyl-α-D-glucopyranoside as substrate. Inhibitory activity against porcine pancreatic α-amylase was performed using 1 mM of 2-chloro-4 nitrophenol-α-D-maltotroside-3 as substrate. Nitrophenol product was spectrophotometrically measured at 405 nm. Anticancer activity was evaluated against five human cancer cell lines compared to two human normal cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Mango leaf extract and mangiferin exhibited dose-dependent inhibition against yeast α-glucosidase with the IC50 of 0.0503 and 0.5813 mg/ml, respectively, against rat α-glucosidase with the IC50 of 1.4528 and 0.4333 mg/ml, respectively, compared to acarbose with the IC50 of 11.9285 and 0.4493 mg/ml, respectively. For anticancer activity, mango leaf extract, at ≥200 μg/ml showed cytotoxic potential against all tested cancer cell lines. In conclusion, mango leaf possessed antidiabetic and anticancer potential in vitro. PMID:28217550

  6. Anticancer Activity of Linalool Terpenoid: Apoptosis Induction and ...

    African Journals Online (AJOL)

    Anticancer Activity of Linalool Terpenoid: Apoptosis Induction and Cell Cycle Arrest in ... of linalool on cell morphology and apoptotic body formation in DU145 cells ... It was observed that 4.36, 11.54, 21.88 and 15.54 % of the cells underwent ...

  7. An Insight into the Anticancer Activities of Ru(II-Based Metallocompounds Using Docking Methods

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    Peter A. Ajibade

    2013-09-01

    Full Text Available Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds.

  8. Synthesis and Anticancer Activity of Novel Thiazole-5-Carboxamide Derivatives

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    Wen-Xi Cai

    2016-01-01

    Full Text Available A series of novel 2-phenyl-4-trifluoromethyl thiazole-5-carboxamide derivatives have been synthesized and evaluated for their anticancer activity against A-549, Bel7402, and HCT-8 cell lines. Among the tested compounds, highest activity (48% was achieved with the 4-chloro-2-methylphenyl amido substituted thiazole containing the 2-chlorophenyl group on the two position of the heterocyclic ring. Other structurally similar compounds displayed moderate activity. The key intermediates have been fully characterized.

  9. Anticancer Activity of Tetrahydrocorysamine against Pancreatic ...

    African Journals Online (AJOL)

    Pancreatic Adenocarcinoma Cell Line PANC-1 In vitro and ... Purpose: To investigate the cytotoxic activity of tetrahydrocorysamine (TCSM) from Corydalis Rhizoma .... Health Guide concerning the Care and Use of .... activity of compound is related to apoptosis [13]. ... Yahusuo on six human gastric cancer cell lines in vitro.

  10. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

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    Chi H.J. Kao

    2013-02-01

    Full Text Available ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides being widely known as the major active ingredients, the different biological pathways by which they exert their anti-cancer effect remain poorly defined. Therefore, understanding the mechanisms of action may lead to more widespread use of Ganoderma as an anti-cancer agent.The aim of this paper is to summarise the various bioactive mechanisms that have been proposed for the anti-cancer properties of triterpenes and polysaccharides extracted from G. lucidum. A literature search of published papers on NCBI with keywords “Ganoderma” and “cancer” was performed. Among those, studies which specifically examined the anti-cancer activities of Ganoderma triterpenes and polysaccharides were selected to be included in this paper.We have found five potential mechanisms which are associated with the anti-cancer activities of Ganoderma triterpenes and three potential mechanisms for Ganoderma polysaccharides. In addition, G. lucidum has been used in combination with known anti-cancer agents to improve the anti-cancer efficacies. This suggests Ganoderma’s bioactive pathways may compliment that of anti-cancer agents. In this paper we present several potential anti-cancer mechanisms of Ganoderma triterpenes and polysaccharides which can be used for the development of Ganoderma as an anti-cancer agent.

  11. Antimicrobial, antioxidant and anticancer activities of Strychnos ...

    African Journals Online (AJOL)

    Background: Strychnos lucida R. Br. (Loganiaceae), a well-known indigenous medicine in Timor Leste, has been used for the treatment of ailments such as malaria, diarrhoea, fever, hypertension, cancer, diabetes mellitus and skin infections. Its pharmacological activity has never been reported. The aim of this study was to ...

  12. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  13. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.; Bajic, Vladimir B.

    2010-01-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  14. Pinus Roxburghii essential oil anticancer activity and chemical composition evaluation.

    Science.gov (United States)

    Sajid, Arfaa; Manzoor, Qaisar; Iqbal, Munawar; Tyagi, Amit Kumar; Sarfraz, Raja Adil; Sajid, Anam

    2018-01-01

    The present study was conducted to appraise the anticancer activity of Pinus roxburghii essential oil along with chemical composition evaluation. MTT assay revealed cytotoxicity induction in colon, leukemia, multiple myeloma, pancreatic, head and neck and lung cancer cells exposed to essential oil. Cancer cell death was also observed through live/dead cell viability assay and FACS analysis. Apoptosis induced by essential oil was confirmed by cleavage of PARP and caspase-3 that suppressed the colony-forming ability of tumor cells and 50 % inhibition occurred at a dose of 25 μg/mL. Moreover, essential oil inhibited the activation of inflammatory transcription factor NF-κB and inhibited expression of NF-κB regulated gene products linked to cell survival (survivin, c-FLIP, Bcl-2, Bcl-xL, c-Myc, c-IAP2), proliferation (Cyclin D1) and metastasis (MMP-9). P. roxburghii essential oil has considerable anticancer activity and could be used as anticancer agent, which needs further investigation to identify and purify the bioactive compounds followed by in vivo studies.

  15. Isoflavones from Calpurnia Aurea subsp. Aurea and their anticancer activity

    CSIR Research Space (South Africa)

    Korir, E

    2014-01-01

    Full Text Available the renal, melanoma and breast cancer cell lines tested against, with the isoflavones 2 and 5 showing the best activity of the compounds tested. These isoflavones may have a synergistic effect with other anticancer drugs. ... activity against breast (MCF7), renal (TK10) and melanoma (UACC62) human cell lines using an in house method developed at the CSIR, South Africa. Results: The isoflavones, 4′,5,7-trihydroxyisoflavone (1), 7,3′- dihydroxy-5′-methoxyisoflavone (2), 7...

  16. Anti-cancer activity of compounds from Bauhinia strychnifolia stem.

    Science.gov (United States)

    Yuenyongsawad, Supreeya; Bunluepuech, Kingkan; Wattanapiromsakul, Chatchai; Tewtrakul, Supinya

    2013-11-25

    The stem and root of Bauhinia strychnifolia Craib (Fabaceae family) have been traditionally used in Thailand to treat fever, alcoholic toxication, allergy and cancer. An EtOH extract of Bauhinia strychnifolia showed good inhibitory activity against several cancer cell lines including HT-29, HeLa, MCF-7 and KB. As there has been no previous reports on chemical constituents of Bauhinia strychnifolia, this study is aimed to isolate the pure compounds with anti-cancer activity. Five pure compounds were isolated from EtOH extract of Bauhinia strychnifolia stem using silica gel, dianion HP-20 and sephadex LH-20 column chromatography and were tested for their cytotoxic effects against HT-29, HeLa, MCF-7 and KB cell lines using the Sulforhodamine B (SRB) assay. Among five compounds, 3,5,7,3',5'-pentahydroxyflavanonol-3-O-α-l-rhamnopyranoside (2) possessed very potent activity against KB (IC₅₀=0.00054μg/mL), HT-29 (IC₅₀=0.00217 μg/mL), MCF-7 (IC₅₀=0.0585 μg/mL) and HeLa cells (IC₅₀=0.0692 μg/mL). 3,5,7-Trihydroxychromone-3-O-α-l-rhamnopyranoside (3) also showed good activity against HT-29 (IC₅₀=0.02366 μg/mL), KB (IC₅₀=0.0412 μg/mL) and MCF-7 (IC₅₀=0.297 μg/mL), respectively. The activity of 2 (IC₅₀=0.00054 μg/mL) against KB cell was ten times higher than that of the positive control, Camptothecin (anti-cancer drug, IC₅₀=0.0057 μg/mL). All compounds did not show any cytotoxicity with normal cells at the concentration of 1 μg/mL. This is the first report of compounds 2 and 3 on anti-cancer activity and based on the anti-cancer activity of extracts and pure compounds isolated from Bauhinia strychnifolia stem, it might be suggested that this plant could be useful for treatment of cancer. © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Synthesis and anticancer structure activity relationship investigation of cationic anthraquinone analogs.

    Science.gov (United States)

    Shrestha, Jaya P; Fosso, Marina Y; Bearss, Jeremiah; Chang, Cheng-Wei Tom

    2014-04-22

    We have synthesized a series of novel 4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-3-ium salts, which can be viewed as analogs of cationic anthraquinones. Unlike the similar analogs that we have reported previously, these compounds show relatively weak antibacterial activities but exert strong anticancer activities (low μM to nM GI50), in particular, against melanoma, colon cancer, non-small cell lung cancer and central nervous system (CNS) cancer. These compounds are structurally different from their predecessors by having the aromatic group, instead of alkyl chains, directly attached to the cationic anthraquinone scaffold. Further investigation in the structure-activity relationship (SAR) reveals the significant role of electron donating substituents on the aromatic ring in enhancing the anticancer activities via resonance effect. Steric hindrance of these groups is disadvantageous but is less influential than the resonance effect. The difference in the attached groups at N-1 position of the cationic anthraquinone analog is the main structural factor for the switching of biological activity from antibacterial to anticancer. The discovery of these compounds may lead to the development of novel cancer chemotherapeutics. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Optimization of gefitinib analogues with potent anticancer activity.

    Science.gov (United States)

    Yin, Kai-Hao; Hsieh, Yi-Han; Sulake, Rohidas S; Wang, Su-Pei; Chao, Jui-I; Chen, Chinpiao

    2014-11-15

    The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    International Nuclear Information System (INIS)

    Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju; Shivashangari, Kanchi Subramanian; Ravikumar, Vilwanathan

    2014-01-01

    The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV–vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. - Highlights: • Biogenic synthesis of copper oxide nanoparticles by leaf extract of Ficus religiosa • Characterized via UV–vis, FT-IR, DLS, FE-SEM with EDAX and XRD • Protein may act as an encapsulating, reducing and stabilizing

  20. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India); Shivashangari, Kanchi Subramanian, E-mail: shivashangari@gmail.com [Regional Forensic Science Laboratory, Tiruchirapalli, Tamilnadu (India); Ravikumar, Vilwanathan, E-mail: ravikumarbdu@gmail.com [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India)

    2014-11-01

    The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV–vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. - Highlights: • Biogenic synthesis of copper oxide nanoparticles by leaf extract of Ficus religiosa • Characterized via UV–vis, FT-IR, DLS, FE-SEM with EDAX and XRD • Protein may act as an encapsulating, reducing and stabilizing

  1. In vivo evaluation on the effects of HemoHIM in promoting anticancer activities and reducing the side-effects of anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sung Kee; Jung, U Hee; Park, Hae Ran; Ju, Eun Jin; Cho, Eun Hee

    2009-07-15

    In this project, we aimed to obtain the preclinical in vivo evaluation data for the development of the herbal composition (HemoHIM) as the auxiliary agent for the anticancer treatment that can reduce the side-effects of anticancer drugs and enhance their anticancer activities. Firstly, in vitro studies showed that HemoHIM did not show any effects on the tumor cell growth inhibition by 2 anticancer drugs (cisplatin, 5-FU), which indicated that at least HemoHIM does not exert any adverse effects on the activities of anticancer drugs. Next, the in vivo studies with mice implanted with tumor cells(B16F0, LLC1) showed that HemoHIM partially enhanced the anticancer activities of drugs (cisplatin, 5-FU), and improved endogenous anticancer immune activities. Furthermore, in the same animal models, HemoHIM effectively reduced the side-effects of anticancer drugs (liver and renal toxicities by cisplatin, immune and hematopoietic disorders by 5-FU). These results collectively showed that HemoHIM can enhance the activities of anticancer drugs and reduce their side-effects in vitro and in vivo and HemoHIM does not exert any adverse effects on the efficacy of anticancer drugs. The results of this project can be utilized as the basic preclinical data for the development and approval of HemoHIM as the auxiliary agent for the anticancer treatment

  2. In vivo evaluation on the effects of HemoHIM in promoting anticancer activities and reducing the side-effects of anticancer drugs

    International Nuclear Information System (INIS)

    Jo, Sung Kee; Jung, U Hee; Park, Hae Ran; Ju, Eun Jin; Cho, Eun Hee

    2009-07-01

    In this project, we aimed to obtain the preclinical in vivo evaluation data for the development of the herbal composition (HemoHIM) as the auxiliary agent for the anticancer treatment that can reduce the side-effects of anticancer drugs and enhance their anticancer activities. Firstly, in vitro studies showed that HemoHIM did not show any effects on the tumor cell growth inhibition by 2 anticancer drugs (cisplatin, 5-FU), which indicated that at least HemoHIM does not exert any adverse effects on the activities of anticancer drugs. Next, the in vivo studies with mice implanted with tumor cells(B16F0, LLC1) showed that HemoHIM partially enhanced the anticancer activities of drugs (cisplatin, 5-FU), and improved endogenous anticancer immune activities. Furthermore, in the same animal models, HemoHIM effectively reduced the side-effects of anticancer drugs (liver and renal toxicities by cisplatin, immune and hematopoietic disorders by 5-FU). These results collectively showed that HemoHIM can enhance the activities of anticancer drugs and reduce their side-effects in vitro and in vivo and HemoHIM does not exert any adverse effects on the efficacy of anticancer drugs. The results of this project can be utilized as the basic preclinical data for the development and approval of HemoHIM as the auxiliary agent for the anticancer treatment

  3. Anticancer and Antioxidant Activity of Bread Enriched with Broccoli Sprouts

    Science.gov (United States)

    Gawlik-Dziki, Urszula; Świeca, Michał; Dziki, Dariusz; Sęczyk, Łukasz; Złotek, Urszula; Różyło, Renata; Kaszuba, Kinga; Ryszawy, Damian; Czyż, Jarosław

    2014-01-01

    This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS) in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities); however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS) was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention. PMID:25050366

  4. Anticancer and Antioxidant Activity of Bread Enriched with Broccoli Sprouts

    Directory of Open Access Journals (Sweden)

    Urszula Gawlik-Dziki

    2014-01-01

    Full Text Available This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities; however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention.

  5. Transportan 10 improves the anticancer activity of cisplatin.

    Science.gov (United States)

    Izabela, Rusiecka; Jarosław, Ruczyński; Magdalena, Alenowicz; Piotr, Rekowski; Ivan, Kocić

    2016-05-01

    The aim of this paper was to examine whether cell-penetrating peptides (CPPs) such as transportan 10 (TP10) or protein transduction domain (PTD4) may improve the anticancer activity of cisplatin (cPt). The complexes of TP10 or PTD4 with cPt were used in the experiments. They were carried out on two non-cancer (HEK293 (human embryonic kidney) and HEL299 (human embryo lung)) and two cancer (HeLa (human cervical cancer) and OS143B (human osteosarcoma 143B)) cell lines. Both complexes were tested (MTT assay) with respect to their anticancer or cytotoxic actions. TAMRA (fluorescent dye)-stained preparations were visualized in a fluorescence microscope. The long-term effect of TP10 + cPt and its components on non-cancer and cancer cell lines was observed in inverted phase contrast microscopy. In the MTT test (cell viability assay), the complex of TP10 + cPt produced a more potent effect on the cancer cell lines (HeLa, OS143B) in comparison to that observed after separate treatment with TP10 or cPt. At the same time, the action of the complex and its components was rather small on non-cancer cell lines. On the other hand, a complex of another CPP with cPt, i.e., PTD4 + cPt, was without a significant effect on the cancer cell line (OS143B). The images of the fluorescent microscopy showed TAMRA-TP10 or TAMRA-TP10 + cPt in the interior of the HeLa cells. In the case of TAMRA-PTD4 or TAMRA-PTD4 + cPt, only the first compound was found inside the cancer cell line. In contrast, none of the tested compounds gained access to the interior of the non-cancer cells (HEK293, HEL299). Long-term incubation with the TP10 + cPt (estimated by inverted phase contrast microscopy) lead to an enhanced action of the complex on cell viability (decrease in the number of cells and change in their morphology) as compared with that produced by each single agent. With regard to the tested CPPs, only TP10 improved the anticancer activity of cisplatin if both compounds were used in the form of a

  6. [Vitamin D anti-cancer activities: observations, doubts and certainties].

    Science.gov (United States)

    Castronovo, C; Castronovo, V; Nikkels, A; Peulen, O

    2015-10-01

    The importance of vitamin D in bone and phosphocalcic status is well recognized by the scientific and medical communities; however, recently identified properties of this cholesterol derived molecule, such as immunomodulator and anticancer activities, are yet discussed. Actually, the debate is not so much about the new vitamin D properties, but rather about the optimal concentration required to reach these properties. The difficulty in determining the norms is rendered even more complex by the existence of a vitamin D receptor gene polymorphism. The body pool of this vitamin depends essentially on its endogenous synthesis, but also on its dietary intakes. Many epidemiological studies interested in Vitamin D serum level and cancer suggest a relation between low Vitamin D level and cancer risk, especially in breast and colon adenocarcinomas. In vitro, many studies showed, in different human and animal malignant cell lines, that this molecule exerts anticancer activities: it induces apoptosis and cell differentiation as well as it inhibits proliferation and angiogenesis. This review tries to update the current knowledge on vitamin D and, more particularly, the potential interest of this molecule in cancer prevention and management.

  7. Biological and therapeutic activities, and anticancer properties of curcumin.

    Science.gov (United States)

    Perrone, Donatella; Ardito, Fatima; Giannatempo, Giovanni; Dioguardi, Mario; Troiano, Giuseppe; Lo Russo, Lucio; DE Lillo, Alfredo; Laino, Luigi; Lo Muzio, Lorenzo

    2015-11-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Curcumin has been used extensively in Ayurvedic medicine, as it is nontoxic and exhibits a variety of therapeutic properties, including antioxidant, analgesic, anti-inflammatory and antiseptic activities. Recently, certain studies have indicated that curcumin may exert anticancer effects in a variety of biological pathways involved in mutagenesis, apoptosis, tumorigenesis, cell cycle regulation and metastasis. The present study reviewed previous studies in the literature, which support the therapeutic activity of curcumin in cancer. In addition, the present study elucidated a number of the challenges concerning the use of curcumin as an adjuvant chemotherapeutic agent. All the studies reviewed herein suggest that curcumin is able to exert anti-inflammatory, antiplatelet, antioxidative, hepatoprotective and antitumor activities, particularly against cancers of the liver, skin, pancreas, prostate, ovary, lung and head neck, as well as having a positive effect in the treatment of arthritis.

  8. How strong is the edge effect in the adsorption of anticancer drugs on a graphene cluster?

    Science.gov (United States)

    Rungnim, Chompoonut; Chanajaree, Rungroj; Rungrotmongkol, Thanyada; Hannongbua, Supot; Kungwan, Nawee; Wolschann, Peter; Karpfen, Alfred; Parasuk, Vudhichai

    2016-04-01

    The adsorption of nucleobase-analog anticancer drugs (fluorouracil, thioguanine, and mercaptopurine) on a graphene flake (C54H18) was investigated by shifting the site at which adsorption occurs from one end of the sheet to the other end. The counterpoise-corrected M06-2X/cc-pVDZ binding energies revealed that the binding stability decreases in the sequence thioguanine > mercaptopurine > fluorouracil. We found that adsorption near the middle of the sheet is more favorable than adsorption near the edge due to the edge effect. This edge effect is stronger for the adsorption of thioguanine or mercaptopurine than for fluorouracil adsorption. However, the edge effect reduces the binding energy of the drug to the flake by only a small amount, <5 kcal/mol, depending on the adsorption site and the alignment of the drug at this site.

  9. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

    OpenAIRE

    Chi H.J. Kao; Amalini C. Jesuthasan; Karen S. Bishop; Marcus P. Glucina; Lynnette R. Ferguson

    2013-01-01

    ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides bei...

  10. Anticancer activity of botanical compounds in ancient fermented beverages (review).

    Science.gov (United States)

    McGovern, P E; Christofidou-Solomidou, M; Wang, W; Dukes, F; Davidson, T; El-Deiry, W S

    2010-07-01

    Humans around the globe probably discovered natural remedies against disease and cancer by trial and error over the millennia. Biomolecular archaeological analyses of ancient organics, especially plants dissolved or decocted as fermented beverages, have begun to reveal the preliterate histories of traditional pharmacopeias, which often date back thousands of years earlier than ancient textual, ethnohistorical, and ethnological evidence. In this new approach to drug discovery, two case studies from ancient Egypt and China illustrate how ancient medicines can be reconstructed from chemical and archaeological data and their active compounds delimited for testing their anticancer and other medicinal effects. Specifically, isoscopoletin from Artemisia argyi, artemisinin from Artemisia annua, and the latter's more easily assimilated semi-synthetic derivative, artesunate, showed the greatest activity in vitro against lung and colon cancers. In vivo tests of these compounds previously unscreened against lung and pancreatic cancers are planned for the future.

  11. Characterization of anticancer, DNase and antifungal activity of pumpkin 2S albumin.

    Science.gov (United States)

    Tomar, Prabhat Pratap Singh; Nikhil, Kumar; Singh, Anamika; Selvakumar, Purushotham; Roy, Partha; Sharma, Ashwani Kumar

    2014-06-13

    The plant 2S albumins exhibit a spectrum of biotechnologically exploitable functions. Among them, pumpkin 2S albumin has been shown to possess RNase and cell-free translational inhibitory activities. The present study investigated the anticancer, DNase and antifungal activities of pumpkin 2S albumin. The protein exhibited a strong anticancer activity toward breast cancer (MCF-7), ovarian teratocarcinoma (PA-1), prostate cancer (PC-3 and DU-145) and hepatocellular carcinoma (HepG2) cell lines. Acridine orange staining and DNA fragmentation studies indicated that cytotoxic effect of pumpkin 2S albumin is mediated through induction of apoptosis. Pumpkin 2S albumin showed DNase activity against both supercoiled and linear DNA and exerted antifungal activity against Fusarium oxysporum. Secondary structure analysis by CD showed that protein is highly stable up to 90°C and retains its alpha helical structure. These results demonstrated that pumpkin 2S albumin is a multifunctional protein with host of potential biotechnology applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies

    Directory of Open Access Journals (Sweden)

    Artur Jabłoński

    2017-12-01

    Full Text Available The synthesis of four cymantrene-5-fluorouracil derivatives (1–4 and two cymantrene-adenine derivatives (5 and 6 is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6, together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P21/m space group. The newly synthesized compounds 1–6 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG, five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains, Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S. aureus and S. epidermidis, as well as against the protozoan parasite Trypanosoma brucei. The most cytotoxic compounds were derivatives 2 and C for A549 and SKOV-3 cancer cell lines, respectively, with 50% growth inhibition (IC50 values of about 7 µM. The anticancer activity of the cymantrene compounds was determined to be due to their ability to induce oxidative stress and to trigger apoptosis and autophagy in cancer cells. Three derivatives (1, 4 and 5 displayed promising antitrypanosomal activity, with GI50 values in the low micromolar range (3–4 µM. The introduction of the 5-fluorouracil moiety in 1 enhanced the trypanocidal activity when compared to the activity previously reported for the corresponding uracil derivative. The antibacterial activity of cymantrene compounds 1 and C was within the range of 8–64 µg/mL and seemed to be the result of induced cell shrinking.

  13. Priming anticancer active specific immunotherapy with dendritic cells.

    Science.gov (United States)

    Mocellin, Simone

    2005-06-01

    Dendritic cells (DCs) probably represent the most powerful naturally occurring immunological adjuvant for anticancer vaccines. However, the initial enthusiasm for DC-based vaccines is being tempered by clinical results not meeting expectations. The partial failure of current vaccine formulations is explained by the extraordinary complexity of the immune system, which makes the task of exploiting the potential of such a biotherapeutic approach highly challenging. Clinical findings obtained in humans so far indicate that the immune system can be actively polarized against malignant cells by means of DC-based active specific immunotherapy, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally 'dormant' immune effectors can actually be employed as endogenous weapons against malignant cells. Only the thorough understanding of DC biology and tumor-host immune system interactions will allow researchers to reproduce, in a larger set of patients, the cellular/molecular conditions leading to an effective immune-mediated eradication of cancer.

  14. Characterization and in vitro studies on anticancer activity of ...

    African Journals Online (AJOL)

    SAM

    2014-05-21

    May 21, 2014 ... The exopolymer produced by B. thuringiensis S13, showed potent ... Polysaccharides derived from a microorganism have specific broad .... polymer and cisplatin (an anticancer drug as standard) separately in triplicates to ...

  15. Ultrasound-Assisted Extraction, Antioxidant and Anticancer Activities of the Polysaccharides from Rhynchosia minima Root

    Directory of Open Access Journals (Sweden)

    Xuejing Jia

    2015-11-01

    Full Text Available Box-Behnken design (BBD, one of the most common response surface methodology (RSM methods, was used to optimize the experimental conditions for ultrasound-assisted extraction of polysaccharides from Rhynchosia minima root (PRM. The antioxidant abilities and anticancer activity of purified polysaccharide fractions were also measured. The results showed that optimal extraction parameters were as follows: ultrasound exposure time, 21 min; ratio of water to material, 46 mL/g; ultrasound extraction temperature, 63 °C. Under these conditions, the maximum yield of PRM was 16.95% ± 0.07%. Furthermore, the main monosaccharides of purified fractions were Ara and Gal. PRM3 and PRM5 exhibited remarkable DPPH radical scavenging activities and reducing power in vitro. PRM3 showed strong inhibitory activities on the growth of MCF-7 cells in vitro. The above results indicate that polysaccharides from R. minima root have the potential to be developed as natural antioxidants and anticancer ingredients for the food and pharmaceutical industries.

  16. Ultrasound-Assisted Extraction, Antioxidant and Anticancer Activities of the Polysaccharides from Rhynchosia minima Root.

    Science.gov (United States)

    Jia, Xuejing; Zhang, Chao; Hu, Jie; He, Muxue; Bao, Jiaolin; Wang, Kai; Li, Peng; Chen, Meiwan; Wan, Jianbo; Su, Huanxing; Zhang, Qingwen; He, Chengwei

    2015-11-23

    Box-Behnken design (BBD), one of the most common response surface methodology (RSM) methods, was used to optimize the experimental conditions for ultrasound-assisted extraction of polysaccharides from Rhynchosia minima root (PRM). The antioxidant abilities and anticancer activity of purified polysaccharide fractions were also measured. The results showed that optimal extraction parameters were as follows: ultrasound exposure time, 21 min; ratio of water to material, 46 mL/g; ultrasound extraction temperature, 63 °C. Under these conditions, the maximum yield of PRM was 16.95%±0.07%. Furthermore, the main monosaccharides of purified fractions were Ara and Gal. PRM3 and PRM5 exhibited remarkable DPPH radical scavenging activities and reducing power in vitro. PRM3 showed strong inhibitory activities on the growth of MCF-7 cells in vitro. The above results indicate that polysaccharides from R. minima root have the potential to be developed as natural antioxidants and anticancer ingredients for the food and pharmaceutical industries.

  17. Laser assisted anticancer activity of benzimidazole based metal organic nanoparticles.

    Science.gov (United States)

    Praveen, P A; Ramesh Babu, R; Balaji, P; Murugadas, A; Akbarsha, M A

    2018-03-01

    Recent studies showed that the photothermal therapy can be effectively used for the targeted cancerous cells destruction. Hence, in the present study, benzimidazole based metal organic complex nanoparticles, dichloro cobalt(II) bis-benzimidazole (Co-BMZ) and dichloro copper(II) bis-benzimidazole (Cu-BMZ), were synthesized by reprecipitation method and their anti-cancer activity by means of photothermal effect has been studied. Transmission electron microscopy analysis shows that the particle size of Cu-BMZ is ∼100 nm and Co-BMZ is in the range between 100 and 400 nm. Zeta potential analysis ensures the stability of the synthesized nanoparticles. It is found that the nonlinear absorption of the nanoparticles increases with increase in laser power intensity. Phototoxicity of human lung cancer (A549) and the normal mouse embryonic fibroblast (NIH-3T3) cells was studied using a 650 nm laser. Even though both the cell lines were affected by laser irradiation, A549 cells show higher cell destruction and lower IC 50 values than the normal cells. Docking studies were used to analyse the interaction site and the results showed that the Cu-BMZ molecules have higher dock score than the Co-BMZ molecules. The obtained results indicate that Cu-BMZ samples have lesser particle size, higher nonlinear absorption and higher interaction energy than the Co-BMZ samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Chemopreventive and Anticancer Activities of Allium victorialis var. platyphyllum Extracts.

    Science.gov (United States)

    Kim, Hyun-Jeong; Park, Min Jeong; Park, Hee-Juhn; Chung, Won-Yoon; Kim, Ki-Rim; Park, Kwang-Kyun

    2014-09-01

    Allium victorialis var. platyphyllum is an edible perennial herb and has been used as a vegetable or as a Korean traditional medicine. Allium species have received much attention owing to their diverse pharmacological properties, including antioxidative, anti-inflammatory, and anticancer activities. However, A. victorialis var. platyphyllum needs more study. The chemopreventive potential of A. victorialis var. platyphyllum methanol extracts was examined by measuring 12-O-tetra-decanoylphorbol 13-acetate (TPA)-induced superoxide anion production in the differentiated HL-60 cells, TPA-induced mouse ear edema, and Ames/Salmonella mutagenicity. The apoptosis-inducing capabilities of the extracts were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, 4',6-diamidino-2-phenylindole staining, and the DNA fragmentation assay in human colon cancer HT-29 cells. Antimetastatic activities of the extracts were also investigated in an experimental mouse lung metastasis model. The methanol extracts of A. victorialis var. platyphyllum rhizome (AVP-R) and A. victorialis var. platyphyllum stem (AVP-S) dose-dependently inhibited the TPA-induced generation of superoxide anion in HL-60 cells and TPA-induced ear edema in mice, as well as 7,12-dimethylbenz[a]anthracene (DMBA) and tert-butyl hydroperoxide (t-BOOH) -induced bacterial mutagenesis. AVP-R and AVP-S reduced cell viability in a dose-related manner and induced apoptotic morphological changes and internucleosomal DNA fragmentation in HT-29 cells. In the experimental mouse lung metastasis model, the formation of tumor nodules in lung tissue was significantly inhibited by the treatment of the extracts. AVP-R and AVP-S possess antioxidative, anti-inflammatory, antimutagenic, proapoptotic, and antimetastatic activities. Therefore, these extracts can serve as a beneficial supplement for the prevention and treatment of cancer.

  19. Anticancer and reversing multidrug resistance activities of natural isoquinoline alkaloids and their structure-activity relationship.

    Science.gov (United States)

    Qing, Zhi-Xing; Huang, Jia-Lu; Yang, Xue-Yi; Liu, Jing-Hong; Cao, Hua-Liang; Xiang, Feng; Cheng, Pi; Zeng, Jian-Guo

    2017-09-20

    The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloid (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Novel walnut peptide–selenium hybrids with enhanced anticancer synergism: facile synthesis and mechanistic investigation of anticancer activity

    Directory of Open Access Journals (Sweden)

    Liao W

    2016-04-01

    Full Text Available Wenzhen Liao,1 Rong Zhang,1 Chenbo Dong,2 Zhiqiang Yu,3 Jiaoyan Ren11College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Civil and Environmental Engineering, Rice University, Houston, TX, USA; 3School of Pharmaceutical Science, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaAbstract: This contribution reports a facile synthesis of degreased walnut peptides (WP1-functionalized selenium nanoparticles (SeNPs hybrids with enhanced anticancer activity and a detailed mechanistic evaluation of its superior anticancer activity. Structural and chemical characterizations proved that SeNPs are effectively capped with WP1 via physical absorption, resulting in a stable hybrid structure with an average diameter of 89.22 nm. A panel of selected human cancer cell lines demonstrated high susceptibility toward WP1-SeNPs and displayed significantly reduced proliferative behavior. The as-synthesized WP1-SeNPs exhibited excellent selectivity between cancer cells and normal cells. The targeted induction of apoptosis in human breast adenocarcinoma cells (MCF-7 was confirmed by the accumulation of arrested S-phase cells, nuclear condensation, and DNA breakage. Careful investigations revealed that an extrinsic apoptotic pathway can be attributed to the cell apoptosis and the same was confirmed by activation of the Fas-associated with death domain protein and caspases 3, 8, and 9. In addition, it was also understood that intrinsic apoptotic pathways including reactive oxygen species generation, as well as the reduction in mitochondrial membrane potential, are also involved in the WP1-SeNP-induced apoptosis. This suggested the involvement of multiple apoptosis pathways in the anticancer activity. Our results indicated that WP1-SeNP hybrids with Se core encapsulated in a WP1 shell could be a highly

  1. Potential Anti-Cancer Activities and Mechanisms of Costunolide and Dehydrocostuslactone

    Directory of Open Access Journals (Sweden)

    Xuejing Lin

    2015-05-01

    Full Text Available Costunolide (CE and dehydrocostuslactone (DE are derived from many species of medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have been reported for their wide spectrum of biological effects, including anti-inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant, antidiabetic, antiulcer, and anthelmintic activities. In recent years, they have caused extensive interest in researchers due to their potential anti-cancer activities for various types of cancer, and their anti-cancer mechanisms, including causing cell cycle arrest, inducing apoptosis and differentiation, promoting the aggregation of microtubule protein, inhibiting the activity of telomerase, inhibiting metastasis and invasion, reversing multidrug resistance, restraining angiogenesis has been studied. This review will summarize anti-cancer activities and associated molecular mechanisms of these two compounds for the purpose of promoting their research and application.

  2. Studies of anticancer and antipyretic activity of Bidens pilosa whole ...

    African Journals Online (AJOL)

    . (Asteraceae) has been conducted using the in – vitro comet assay for anticancer and the antipyretic action, which was done with in – vivo models. The extract from whole plant was extracted with n – hexane, chloroform and methanol extract ...

  3. Eco-friendly approach for nanoparticles synthesis and mechanism behind antibacterial activity of silver and anticancer activity of gold nanoparticles.

    Science.gov (United States)

    Patil, Maheshkumar Prakash; Kim, Gun-Do

    2017-01-01

    This review covers general information about the eco-friendly process for the synthesis of silver nanoparticles (AgNP) and gold nanoparticles (AuNP) and focuses on mechanism of the antibacterial activity of AgNPs and the anticancer activity of AuNPs. Biomolecules in the plant extract are involved in reduction of metal ions to nanoparticle in a one-step and eco-friendly synthesis process. Natural plant extracts contain wide range of metabolites including carbohydrates, alkaloids, terpenoids, phenolic compounds, and enzymes. A variety of plant species and plant parts have been successfully extracted and utilized for AgNP and AuNP syntheses. Green-synthesized nanoparticles eliminate the need for a stabilizing and capping agent and show shape and size-dependent biological activities. Here, we describe some of the plant extracts involved in nanoparticle synthesis, characterization methods, and biological applications. Nanoparticles are important in the field of pharmaceuticals for their strong antibacterial and anticancer activity. Considering the importance and uniqueness of this concept, the synthesis, characterization, and application of AgNPs and AuNPs are discussed in this review.

  4. Isolation and characterization of Cepa2, a natural alliospiroside A, from shallot (Allium cepa L. Aggregatum group) with anticancer activity.

    Science.gov (United States)

    Abdelrahman, Mostafa; Mahmoud, Hassan Y A H; El-Sayed, Magdi; Tanaka, Shuhei; Tran, L S

    2017-07-01

    Exploration of new and promising anticancer compounds continues to be one of the main tasks of cancer research because of the drug resistance, high cytotoxicity and limitations of tumor selectivity. Natural products represent a better choice for cancer treatment in comparison with synthetic compounds because of their pharmacokinetic properties and lower side effects. In the current study, we isolated a steroidal saponin, named Cepa2, from the dry roots of shallot (Allium cepa L. Aggregatum group), and determined its structure by using two-dimensional nuclear manganic resonance (2D NMR). The 1 H NMR and 13 C NMR data revealed that the newly isolated Cepa2 compound is identical to alliospiroside A (C 38 H 60 O 12 ) [(25S)-3β-hydroxyspirost-5-en-1β-yl-2-O-(6-deoxy-α-L-mannopyranosyl)-α-L-arabinopyranoside], whose anticancer activity remains elusive. Our in vitro examination of the cytotoxic activity of the identified Cepa2 against P3U1 myeloma cancer cell line showed its high efficiency as an anticancer with 91.13% reduction in P3U1 cell viability 12 h post-treatment. The reduction of cell viability was correlated with the increase in reactive oxygen species levels in Cepa2-treated P3U1 cells, as compared with untreated cells. Moreover, scanning electron microscope results demonstrated apoptosis of the Cepa2-treated P3U1 cells in a time course-dependent manner. The results of our study provide evidence for the anticancer properties of the natural Cepa2/alliospiroside A extracted from shallot plants, and a strong foundation for in-depth investigations to build theoretical bases for cell apoptosis and development of novel anticancer drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Facile synthesis of ferromagnetic Ni doped CeO{sub 2} nanoparticles with enhanced anticancer activity

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, Fazal; Jan, Tariq [Laboratory of Nanoscience and Technology, Department of Physics, International Islamic University Islamabad (Pakistan); Iqbal, Javed, E-mail: javed.saggu@iiu.edu.pk [Laboratory of Nanoscience and Technology, Department of Physics, International Islamic University Islamabad (Pakistan); Ahmad, Ishaq [Experimental Physics Labs, National Center for Physics, Islamabad (Pakistan); Naqvi, M. Sajjad H. [Department of Biochemistry, University of Karachi, Karachi (Pakistan); Malik, Maaza [UNESCO-UNISA Africa Chair in Nanosciences/Nanotechnology, College of Graduate Studies, University of South Africa, Muckleneuk Ridge, PO Box 392, Pretoria (South Africa); Nanosciences African Network (NANOAFNET), iThemba LABS-National Research Foundation, 1 Old Faure Road, Somerset West 7129, PO Box 722, Somerset West, Western Cape Province (South Africa)

    2015-12-01

    Highlights: • The synthesized undoped and Ni doped CeO{sub 2} nanoparticles exhibited RTFM. • Oxygen vacancies and magnetic ions both were believed to be responsible for RTFM. • The prepared nanoparticles exhibited selective cytotoxicity. • Ni doping enhanced the anticancer activity of CeO{sub 2} nanoparticles. • Differential ROS generation was observed to control their cytotoxicity. - Abstract: Ni{sub x}Ce{sub 1−x}O{sub 2} (where x = 0, 0.01, 0.03, 0.05 and 0.07) nanoparticles were synthesized by soft chemical method and were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman, UV–vis absorption spectroscopy and vibrating sample magnetometer (VSM). XRD and Raman results indicated the formation of single phase cubic fluorite structure for the synthesized nanoparticles. Ni dopant induced excessive structural changes such as decrease in crystallite size as well as lattice constants and enhancement in oxygen vacancies in CeO{sub 2} crystal structure. These structural variations significantly influenced the optical and magnetic properties of CeO{sub 2} nanoparticles. The synthesized Ni{sub x}Ce{sub 1−x}O{sub 2} nanoparticles exhibited room temperature ferromagnetic behavior. Ni doping induced effects on the cytotoxicity of CeO{sub 2} nanoparticles were examined against HEK-293 healthy cell line and SH-SY5Y neuroblastoma cancer cell line. The prepared Ni{sub x}Ce{sub 1−x}O{sub 2} nanoparticles demonstrated differential cytotoxicity. Furthermore, anticancer activity of CeO{sub 2} nanoparticles observed to be significantly enhanced with Ni doping which was found to be strongly correlated with the level of reactive oxygen species (ROS) production. The prepared ferromagnetic Ni{sub x}Ce{sub 1−x}O{sub 2} nanoparticles with differential cytotoxic nature may be potential for future targeted cancer therapy.

  6. Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

    Science.gov (United States)

    2014-01-01

    Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. Results In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. Conclusions These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity. PMID:24962785

  7. Coevolution between human's anticancer activities and functional foods from crop origin center in the world.

    Science.gov (United States)

    Zeng, Ya-Wen; Du, Juan; Pu, Xiao-Ying; Yang, Jia-Zhen; Yang, Tao; Yang, Shu-Ming; Yang, Xiao-Meng

    2015-01-01

    Cancer is the leading cause of death around the world. Anticancer activities from many functional food sources have been reported in years, but correlation between cancer prevalence and types of food with anticancer activities from crop origin center in the world as well as food source with human migration are unclear. Hunger from food shortage is the cause of early human evolution from Africa to Asia and later into Eurasia. The richest functional foods are found in crop origin centers, housing about 70% in the world populations. Crop origin centers have lower cancer incidence and mortality in the world, especially Central Asia, Middle East, Southwest China, India and Ethiopia. Asia and Africa with the richest anticancer crops is not only the most important evolution base of humans and origin center of anticancer functional crop, but also is the lowest mortality and incidence of cancers in the world. Cancer prevention of early human migrations was associated with functional foods from crop origin centers, especially Asia with four centers and one subcenter of crop origin, accounting for 58% of the world population. These results reveal that coevolution between human's anticancer activities associated with functional foods for crop origin centers, especially in Asia and Africa.

  8. In vitro investigating of anticancer activity of focuxanthin from marine brown seaweed species

    Directory of Open Access Journals (Sweden)

    M. Karkhane Yousefi

    2018-01-01

    Full Text Available Breast cancer is the most common cancer type among women all over the world. Chemotherapy is the use of anticancer medicines for treating cancer but it has many side effects and cells may become resistant to these chemical medicines. Therefore, finding new compounds of natural origin could be a promising solution to this problem. The aim of the current study was to evaluate anticancer activity of fucoxanthin which is the most important carotenoid found in the marine brown seaweeds and diatoms. fucoxanthin has many properties (antioxidant, antibacterial, anticancer, antiobesity, anti-inflammatory and etc. due to its unique structure. Samples with different concentrations (10, 25 and 50 µg/ml and at various incubation times were collected (6, 24 and 48 hours from four different species (Padina tenuis, Colpomenia sinuosa, Iyengaria stellate and Dictyota indica of brown seaweeds from Qeshm Island, Persian Gulf. Moreover, the anticancer activity of fucoxanthin-containing extracts on breast cancer cells line and normal human skin fibroblast cells line was assessed by MTT [3-(4,5-dimethylthiazolyl-2,5-diphenyl-tetrazolium bromide] assay to specify the cytotoxic effects. The results showed that fucoxanthin extract from Dictyota. indica at 24-hour treatment and 50 µg/ml concentration has the most effective anticancer activity on the breast cancer cells line, without toxic effects to the normal cells. According to the obtained results, it seems that Dictyota. Indica is a good candidate for further analysis and can be introduced to the food and pharmaceutical industries.

  9. Potential anticancer activity of curcumin analogs containing sulfone on human cancer cells

    Directory of Open Access Journals (Sweden)

    Zhang Qiuyan

    2016-01-01

    Full Text Available Three curcumin analogs(S1-S3 containing sulfone were investigated for their effects on human prostate cancer PC-3, colon cancer HT-29, lung cancer H1299 and pancreatic cancer BxPC-3 cells. The three compounds were approximately 16-to 96-fold more active than curcumin in these cell lines as determined by the MTT assay. The effects of these compounds on cell growth were further studied in prostate cancer PC-3 cells in both two dimensional (2D and three dimensional (3D cultures. S1-S3strongly inhibited the growth and induced cell death in PC-3 cells, and the effects of these compounds were associated with suppression of nuclear factor kappa B (NF-κB transcriptional activity. Moreover, treatment of PC-3 cells with all three compounds caused a decrease in the level of phosphorylated signal transducer and activator of transcription-3 (p-STAT3 (Tyr705,but not p-STAT3(Ser727. Only S1and S2decreased the presence of phosphorylated Akt (p-Akt in PC-3 cells. These curcumin analogs warrant further in vivo studies for anticancer activities in suitable animal models.

  10. Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro

    Czech Academy of Sciences Publication Activity Database

    Bhambra, A.S.; Edgar, M.; Elsegood, M.R.J.; Horsburgh, L.; Kryštof, Vladimír; Lucas, P.D.; Mojally, M.; Teat, S. J.; Warwick, T.G.; Weaver, G.W.; Zeinali, F.

    2016-01-01

    Roč. 188, AUG (2016), s. 99-109 ISSN 0022-1139 R&D Projects: GA ČR(CZ) GA15-15264S Institutional support: RVO:61389030 Keywords : Anticancer activity * Benzimidazole * C-F activation Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.101, year: 2016

  11. Anticancer Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin Delivery

    Directory of Open Access Journals (Sweden)

    Yuan-Seng Wu

    2017-10-01

    Full Text Available Surfactin, a cyclic lipopeptide biosurfactant produced by various strains of Bacillus genus, has been shown to induce cytotoxicity against many cancer types, such as Ehrlich ascites, breast and colon cancers, leukemia and hepatoma. Surfactin treatment can inhibit cancer progression by growth inhibition, cell cycle arrest, apoptosis, and metastasis arrest. Owing to the potent effect of surfactin on cancer cells, numerous studies have recently investigated the mechanisms that underlie its anticancer activity. The amphiphilic nature of surfactin allows its easy incorporation nano-formulations, such as polymeric nanoparticles, micelles, microemulsions, liposomes, to name a few. The use of nano-formulations offers the advantage of optimizing surfactin delivery for an improved anticancer therapy. This review focuses on the current knowledge of surfactin properties and biosynthesis; anticancer activity against different cancer models and the underlying mechanisms involved; as well as the potential application of nano-formulations for optimal surfactin delivery.

  12. Synthesis and structure-activity relationship exploration of some potent anti-cancer phenyl amidrazone derivatives.

    Science.gov (United States)

    Habashneh, Almeqdad Y; El-Abadelah, Mustafa M; Bardaweel, Sanaa K; Taha, Mutasem O

    2017-12-04

    Amidrazones have been reported to have significant anti-tumor properties against several cancer cell lines. The current project aims to profile the structure-anticancer activity relationship of phenyl-amidrazons. Fifteen phenyl-amidrazone-piperazine derivatives were prepared and tested against four cancer cell lines (leukemia, prostate, breast and colon cancers). Six compounds illustrated low micromolar anticancer IC50 values, while the remaining compounds were either inactive or of moderate potencies. All compounds were virtually nontoxic against normal fibroblast cells. Docking into the oncogenic kinase bcr/abl illustrated the critical importance of (i) p-halogen substituent on the ligand's phenyl ring and (ii) the presence of positive ionizable moiety at the ligand's piperazine fragment for anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Anticancer Activity, Antioxidant Activity, and Phenolic and Flavonoids Content of Wild Tragopogon porrifolius Plant Extracts

    Directory of Open Access Journals (Sweden)

    Fuad Al-Rimawi

    2016-01-01

    Full Text Available Tragopogon porrifolius, commonly referred to as white salsify, is an edible herb used in folk medicine to treat cancer. Samples of Tragopogon porrifolius plant grown wild in Palestine were extracted with different solvents: water, 80% ethanol, and 100% ethanol. The extracts were analyzed for their total phenolic content (TPC, total flavonoid content (TFC, and antioxidant activity (AA. Four different antioxidant assays were used to evaluate AA of the extracts: two measures the reducing power of the extracts (ferric reducing antioxidant power (FRAP and cupric reducing antioxidant power (CUPRAC, while two other assays measure the scavenging ability of the extracts (2,2-azino-di-(3-ethylbenzothialozine-sulphonic acid (ABTS and 2,2-diphenyl-1-picrylhydrazyl (DPPH. Anticancer activity of the plant extracts were also tested on HOS and KHOS osteosarcoma cell lines. The results revealed that the polarity of the extraction solvent affects the TPC, TFC, and AA. It was found that both TPC and AA are highest for plant extracted with 80% ethanol, followed by water, and finally with 100% ethanol. TFC however was the highest in the following order: 80% ethanol > 100% ethanol > water. The plant extracts showed anticancer activities against KHOS cancer cell lines; they reduced total cell count and induced cell death in a drastic manner.

  14. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents.

    Directory of Open Access Journals (Sweden)

    Jiaolin Bao

    Full Text Available Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU, camptothecin (CPT, and paclitaxel (TAX. The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.

  15. Plant derived substances with anti-cancer activity: from folklore to practice

    Directory of Open Access Journals (Sweden)

    Marcelo eFridlender

    2015-10-01

    Full Text Available Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early 19th century. This trend led to the discovery of different active compounds that are derived from plants. In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity. Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next 2 decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities. Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin and cannabinoids. In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity.

  16. Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

    Science.gov (United States)

    Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

    2017-12-01

    Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

  17. Anti-leishmanial and Anti-cancer Activities of a Pentacyclic ...

    African Journals Online (AJOL)

    Erah

    against promastigotes of Leishmania donovani, and anti-cancer activity on K562 leukaemic cell line. Results: A .... crisis of chronic myeloid leukemia was used for this test. The cells ... containing 1×106 cells/ml, 2 mM L-glutamine and 50 µg/ml ...

  18. Anticancer activity of eco-friendly gold nanoparticles against lung and liver cancer cells

    OpenAIRE

    S. Rajeshkumar

    2016-01-01

    Gold nanoparticles have many applications in biomedical field. Improving delivery of anticancer agents to tumors using nanoparticles is one of the most promising research arenas in the field of nanotechnology. Eco-friendly gold nanoparticles synthesis was studied using marine bacteria Enterococcus sp. The nanoparticle synthesis started at 2 h of incubation time was identified by the formation of ruby red in the reaction mixture and SPR band centered at 545 nm. XRD shows that the strong four i...

  19. Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities.

    Science.gov (United States)

    Akhtar, Jawaid; Khan, Ahsan Ahmed; Ali, Zulphikar; Haider, Rafi; Shahar Yar, M

    2017-01-05

    The present review article offers a detailed account of the design strategies employed for the synthesis of nitrogen-containing anticancer agents. The results of different studies describe the N-heterocyclic ring system is a core structure in many synthetic compounds exhibiting a broad range of biological activities. Benzimidazole, benzothiazole, indole, acridine, oxadiazole, imidazole, isoxazole, pyrazole, triazoles, quinolines and quinazolines including others drugs containing pyridazine, pyridine and pyrimidines are covered. The following studies of these compounds suggested that these compounds showed their antitumor activities through multiple mechanisms including inhibiting protein kinase (CDK, MK-2, PLK1, kinesin-like protein Eg5 and IKK), topoisomerase I and II, microtubule inhibition, and many others. Our concise representation exploits the design and anticancer potency of these compounds. The direct comparison of anticancer activities with the standard enables a systematic analysis of the structure-activity relationship among the series. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Synthesis, anticancer and antibacterial activity of salinomycin N-benzyl amides.

    Science.gov (United States)

    Antoszczak, Michał; Maj, Ewa; Napiórkowska, Agnieszka; Stefańska, Joanna; Augustynowicz-Kopeć, Ewa; Wietrzyk, Joanna; Janczak, Jan; Brzezinski, Bogumil; Huczyński, Adam

    2014-11-25

    A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.

  1. Anticancer activity of Cynodon dactylon and Oxalis corniculata on Hep2 cell line.

    Science.gov (United States)

    Salahuddin, H; Mansoor, Q; Batool, R; Farooqi, A A; Mahmood, T; Ismail, M

    2016-04-30

    Bioactive chemicals isolated from plants have attracted considerable attention over the years and overwhelmingly increasing laboratory findings are emphasizing on tumor suppressing properties of these natural agents in genetically and chemically induced animal carcinogenesis models. We studied in vitro anticancer activity of organic extracts of Cynodon dactylon and Oxalis corniculata on Hep2 cell line and it was compared with normal human corneal epithelial cells (HCEC) by using MTT assay. Real Time PCR was conducted for p53 and PTEN genes in treated cancer cell line. DNA fragmentation assay was also carried out to note DNA damaging effects of the extracts. The minimally effective concentration of ethanolic extract of Cynodon dactylon and methanolic extract of Oxalis corniculata that was nontoxic to HCEC but toxic to Hep2 was recorded (IC50) at a concentration of 0.042mg/ml (49.48 % cell death) and 0.048mg/ml (47.93% cell death) respectively, which was comparable to the positive control. Our results indicated dose dependent increase in cell death. P53 and PTEN did not show significant increase in treated cell line. Moreover, DNA damaging effects were also not detected in treated cancer cell line. Anticancer activity of these plants on the cancer cell line showed the presence of anticancer components which should be characterized to be used as anticancer therapy.

  2. GC-MS analysis, Antibacterial, Antioxidant and Anticancer activity of essential oil of Pinus roxburghii from Kashmir, India

    Directory of Open Access Journals (Sweden)

    Wajaht A. Shah

    2014-05-01

    Full Text Available This work was carried out to evaluate chemical composition, antibacterial, antioxidant and anticancer activity of Pinus roxburghii essential oil. The oil was extracted by hydro-distillation which was analysed through GC-MS. The antibacterial activity was evaluated by agar well diffusion method and antioxidant activity was evaluated through DPPH assay while as anticancer activity was evaluated through MTT method. Alpha-pinene and beta-pinene were the major constituents present in the oil. This oil showed significant antibacterial and anticancer activity

  3. Water extract of Ashwagandha leaves has anticancer activity: identification of an active component and its mechanism of action.

    Directory of Open Access Journals (Sweden)

    Renu Wadhwa

    Full Text Available BACKGROUND: Cancer is a leading cause of death accounting for 15-20% of global mortality. Although advancements in diagnostic and therapeutic technologies have improved cancer survival statistics, 75% of the world population live in underdeveloped regions and have poor access to the advanced medical remedies. Natural therapies hence become an alternative choice of treatment. Ashwagandha, a tropical herb used in Indian Ayurvedic medicine, has a long history of its health promoting and therapeutic effects. In the present study, we have investigated an anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX. METHODOLOGY/PRINCIPAL FINDINGS: Anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX was detected by in vitro and in vivo assays. Bioactivity-based size fractionation and NMR analysis were performed to identify the active anticancer component(s. Mechanism of anticancer activity in the extract and its purified component was investigated by biochemical assays. We report that the ASH-WEX is cytotoxic to cancer cells selectively, and causes tumor suppression in vivo. Its active anticancer component was identified as triethylene glycol (TEG. Molecular analysis revealed activation of tumor suppressor proteins p53 and pRB by ASH-WEX and TEG in cancer cells. In contrast to the hypophosphorylation of pRB, decrease in cyclin B1 and increase in cyclin D1 in ASH-WEX and TEG-treated cancer cells (undergoing growth arrest, normal cells showed increase in pRB phosphorylation and cyclin B1, and decrease in cyclin D1 (signifying their cell cycle progression. We also found that the MMP-3 and MMP-9 that regulate metastasis were down regulated in ASH-WEX and TEG-treated cancer cells; normal cells remained unaffected. CONCLUSION: We provide the first molecular evidence that the ASH-WEX and TEG have selective cancer cell growth arrest activity and hence may offer natural and economic resources for anticancer medicine.

  4. Isolation, structure elucidation and anticancer activity from Brevibacillus brevis EGS 9 that combats Multi Drug Resistant actinobacteria.

    Science.gov (United States)

    Arumugam, T; Senthil Kumar, P; Hemavathy, R V; Swetha, V; Karishma Sri, R

    2018-02-01

    Actinobacteria is the most widely distributed organism in the mangrove environment and produce a large amount of secondary metabolites. A new environmental actinobacterial stain exhibited strong antimicrobial activity against vancomycin and methicillin resistant actinobacteria. The active producer strain was found to be as Brevibacillus brevis EGS9, which was confirmed by its morphological, biochemical characteristics and 16S rRNA gene sequencing. It was deposited in NCBI GeneBank database and received with an accession number of KX388147. Brevibacillus brevis EGS9 was cultivated by submerged fermentation to produce antimicrobial compounds. The anti-proliferative agent was extracted from Brevibacillus brevis EGS9 with ethyl acetate. The bioactive metabolites of mangrove actinobacteria was identified by Liquid chromatography with mass spectrometry analysis. The result of the present investigation revealed that actinobacteria isolated from mangroves are potent source of anticancer activity. The strain of Brevibacillus brevis EGS9 exhibited a potential in vitro anticancer activity. The present research concluded that the actinobacteria isolated from mangrove soil sediment are valuable in discovery of novel species. Copyright © 2017. Published by Elsevier Ltd.

  5. Anticancer and enhanced antimicrobial activity of biosynthesizd silver nanoparticles against clinical pathogens

    Science.gov (United States)

    Rajeshkumar, Shanmugam; Malarkodi, Chelladurai; Vanaja, Mahendran; Annadurai, Gurusamy

    2016-07-01

    The present investigation shows the biosynthesis of eco-friendly silver nanoparticles using culture supernatant of Enterococcus sp. and study the effect of enhanced antimicrobial activity, anticancer activity against pathogenic bacteria, fungi and cancer cell lines. Silver nanoparticles was synthesized by adding 1 mM silver nitrate into the 100 ml of 24 h freshly prepared culture supernatant of Enterococcus sp. and were characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Selected Area Diffraction X-Ray (SAED), Energy Dispersive X Ray (EDX) and Fourier Transform Infra red Spectroscopy (FT-IR). The synthesized silver nanoparticles were impregnated with commercial antibiotics for evaluation of enhanced antimicrobial activity. Further these synthesized silver nanoparticles were assessed for its anticancer activity against cancer cell lines. In this study crystalline structured nanoparticles with spherical in the size ranges from 10 to 80 nm and it shows excellent enhanced antimicrobial activity than the commercial antibiotics. The in vitro assay of silver nanoparticles on anticancer have great potential to inhibit the cell viability. Amide linkages and carboxylate groups of proteins from Enterococcus sp. may bind with silver ions and convert into nanoparticles. The activities of commercial antibiotics were enhanced by coating silver nanoparticles shows significant improved antimicrobial activity. Silver nanoparticles have the great potential to inhibit the cell viability of liver cancer cells lines (HepG2) and lung cancer cell lines (A549).

  6. Antibacterial and anticancer activity of seaweeds and bacteria associated with their surface

    OpenAIRE

    Villarreal-Gómez, Luis J; Soria-Mercado, Irma E; Guerra-Rivas, Graciela; Ayala-Sánchez, Nahara E

    2010-01-01

    Marine algae and bacteria are an inexhaustible source of chemical compounds that produce a wide variety of biologically active secondary metabolites. Marine bacteria have become an important target for the biotechnology industry because of the large number of bioactive compounds recently discovered from them. The aim of this study was to evaluate the antibacterial and anticancer activities of extracts from the seaweeds Egregia menziesii, Codium fragile, Sargassum muticum, Endarachne binghamia...

  7. Uptake, delivery, and anticancer activity of thymoquinone nanoparticles in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Fakhoury, Isabelle [American University of Beirut, Department of Biology (Lebanon); Saad, Walid [American University of Beirut, Department of Chemical and Petroleum Engineering (Lebanon); Bouhadir, Kamal [American University of Beirut, Department of Chemistry (Lebanon); Nygren, Peter [Uppsala University, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology (Sweden); Schneider-Stock, Regine [University of Erlangen-Nuremberg, Experimental Tumor Pathology, Institute for Pathology (Germany); Gali-Muhtasib, Hala, E-mail: amro@aub.edu.lb [American University of Beirut, Department of Biology (Lebanon)

    2016-07-15

    Thymoquinone (TQ) is a promising anticancer molecule but its development is hindered by its limited bioavailability. Drug encapsulation is commonly used to overcome low drug solubility, limited bioavailability, and nonspecific targeting. In this project, TQ nanoparticles (TQ-NP) were synthesized and characterized. The cytotoxicity of the NP was investigated in nontumorigenic MCF-10-A breast cells, while the uptake, distribution, as well as the anticancer potential were investigated in MCF-7 and MDA-MB-231 breast cancer cells. Flash Nanoprecipitation and dynamic light scattering coupled with scanning electron microscopy were used to prepare and characterize TQ-NP prior to measuring their anticancer potential by MTT assay. The uptake and subcellular intake of TQ-NP were evaluated by fluorometry and confocal microscopy. TQ-NP were stable with a hydrodynamic average diameter size around 100 nm. Entrapment efficiency and loading content of TQ-NP were high (around 80 and 50 %, respectively). In vitro, TQ-NP had equal or enhanced anticancer activity effects compared to TQ in MCF-7 and aggressive MDA-MB-231 breast cancer cells, respectively, with no significant cytotoxicity of the blank NP. In addition, TQ and TQ-NP were relatively nontoxic to MCF-10-A normal breast cells. TQ-NP uptake mechanism was both time and concentration dependent. Treatment with inhibitors of endocytosis suggested the involvement of caveolin in TQ-NP uptake. This was further confirmed by subcellular localization findings showing the colocalization of TQ-NP with caveolin and transferrin as well as with the early and late markers of endocytosis. Altogether, the results describe an approach for the enhancement of TQ anticancer activity and uncover the mechanisms behind cell-TQ-NP interaction.Graphical Abstract.

  8. Anticancer activities of bovine and human lactoferricin-derived peptides

    NARCIS (Netherlands)

    Arias, M.; Hilchie, A.L.; Haney, E.F.; Bolscher, J.G.M.; Hyndman, M.E.; Hancock, R.E.W.; Vogel, H.J.

    2017-01-01

    Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits

  9. GC-MS analysis, Antibacterial, Antioxidant and Anticancer activity of essential oil of Pinus roxburghii from Kashmir, India

    OpenAIRE

    Wajaht A. Shah; Mahpara Qadir; Javid A. Banday

    2014-01-01

    This work was carried out to evaluate chemical composition, antibacterial, antioxidant and anticancer activity of Pinus roxburghii essential oil. The oil was extracted by hydro-distillation which was analysed through GC-MS. The antibacterial activity was evaluated by agar well diffusion method and antioxidant activity was evaluated through DPPH assay while as anticancer activity was evaluated through MTT method. Alpha-pinene and beta-pinene were the major constituents present in the oil. This...

  10. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models.

    Science.gov (United States)

    Plengsuriyakarn, Tullayakorn; Viyanant, Vithoon; Eursitthichai, Veerachai; Picha, Porntipa; Kupradinun, Piengchai; Itharat, Arunporn; Na-Bangchang, Kesara

    2012-03-27

    Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO

  11. A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Josinete B. Vieira

    2014-07-01

    Full Text Available The Density Functional Theory (DFT method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA and hierarchical cluster analysis (HCA were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS and principal component regression (PCR models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11 = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA, cellular permeability (PCaCO2, cell permeability Maden Darby Canine Kidney (PMDCK, skin permeability (PSkin, plasma protein binding (PPB and penetration of the blood-brain barrier (CBrain/Blood, and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

  12. Antioxidant and Anticancer activities of yeast grown on commercial ...

    African Journals Online (AJOL)

    E-mail: chemist_aml_said@yahoo.com. ABSTRACT ... INTRODUCTION. Yeasts have a positive image with ... production of antioxidant activity compounds. However, the .... were analyzed using an inverted microscope. (Nikon-Japan).

  13. Fatty acid composition and anticancer activity in colon carcinoma cell lines of Prunus dulcis seed oil.

    Science.gov (United States)

    Mericli, Filiz; Becer, Eda; Kabadayı, Hilal; Hanoglu, Azmi; Yigit Hanoglu, Duygu; Ozkum Yavuz, Dudu; Ozek, Temel; Vatansever, Seda

    2017-12-01

    Almond oil is used in traditional and complementary therapies for its numerous health benefits due to high unsaturated fatty acids content. This study investigated the composition and in vitro anticancer activity of almond oil from Northern Cyprus and compared with almond oil from Turkey. Almond oil from Northern Cyprus was obtained by supercritical CO 2 extraction and analyzed by GC-MS. Almond oil of Turkey was provided from Turkish pharmacies. Different concentrations of almond oils were incubated for 24 and 48 h with Colo-320 and Colo-741 cells. Cell growth and cytotoxicity were measured by MTT assays. Anticancer and antiprolifetarive activities of almond oils were investigated by immunocytochemistry using antibodies directed against to BMP-2, β-catenin, Ki-67, LGR-5 and Jagged 1. Oleic acid (77.8%; 75.3%), linoleic acid (13.5%; 15.8%), palmitic acid (7.4%; 6.3%), were determined as the major compounds of almond oil from Northern Cyprus and Turkey, respectively. In the MTT assay, both almond oils were found to be active against Colo-320 and Colo-741 cells with 1:1 dilution for both 24 h and 48 h. As a result of immunohistochemical staining, while both almond oils exhibited significant antiproliferative and anticancer activity, these activities were more similar in Colo-320 cells which were treated with Northern Cyprus almond oil. Almond oil from Northern Cyprus and Turkey may have anticancer and antiproliferative effects on colon cancer cells through molecular signalling pathways and, thus, they could be potential novel therapeutic agents.

  14. Triazole nucleoside derivatives bearing aryl functionalities on the nucleobases show antiviral and anticancer activity.

    Science.gov (United States)

    Xia, Yi; Qu, Fanqi; Peng, Ling

    2010-08-01

    Synthetic nucleoside mimics are important candidates in the searing for antiviral and anticancer drugs. Ribavirin, the first antiviral nucleoside drug, is unique in its antiviral activity with mutilple modes of action, which are mainly due to its special triazole heterocycle as nucleobase. Additionally, introducing aromatic functionalities to the nucleobase is able to confer novel mechanisms of action for nucleoside mimics. With the aim to combine the special characteristics of unnatural triazole heterocycles with those of the appended aromatic groups on the nucleobases, novel 1,2,4-triazole nucleoside analogs bearing aromatic moieties were designed and developed. The present short review summarizes the molecular design, chemical synthesis and biological activity of these triazole nucleoside analogs. Indeed, the discovery of antiviral and anticancer activities shown by these triazole nucleosides as well as the new mechanism underlying the biological activity by one of the anticancer leads has validated the rationale for molecular design and impacted us to further explore the concept with the aim of developing structurally novel nucleoside drug candidates with new modes of action.

  15. Antimicrobial and anticancer activities of porous chitosan-alginate biosynthesized silver nanoparticles.

    Science.gov (United States)

    Venkatesan, Jayachandran; Lee, Jin-Young; Kang, Dong Seop; Anil, Sukumaran; Kim, Se-Kwon; Shim, Min Suk; Kim, Dong Gyu

    2017-05-01

    The main aim of this study was to obtain porous antimicrobial composites consisting of chitosan, alginate, and biosynthesized silver nanoparticles (AgNPs). Chitosan and alginate were used owing to their pore-forming capacity, while AgNPs were used for their antimicrobial property. The developed porous composites of chitosan-alginate-AgNPs were characterized using Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy, X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). The FT-IR results revealed the presence of a strong chemical interaction between chitosan and alginate due to polyelectrolyte complex; whereas, the XRD results confirmed the presence of AgNPs in the composites. The dispersion of AgNPs in the porous membrane was uniform with a pore size of 50-500μm. Antimicrobial activity of the composites was checked with Escherichia coli and Staphylococcus aureus. The developed composites resulted in the formation of a zone of inhibition of 11±1mm for the Escherichia coli, and 10±1mm for Staphylococcus aureus. The bacterial filtration efficiency of chitosan-alginate-AgNPs was 1.5-times higher than that of the chitosan-alginate composite. The breast cancer cell line MDA-MB-231 was used to test the anticancer activity of the composites. The IC 50 value of chitosan-alginate-AgNPs on MDA-MB-231 was 4.6mg. The developed chitosan-alginate-AgNPs composite showed a huge potential for its applications in antimicrobial filtration and cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Evaluation of Antiproliferative Activity of Some Traditional Anticancer ...

    African Journals Online (AJOL)

    antiproliferative activity against six human tumor cell lines (A375.S2, WM1361A, CACO-2, ... presence of cancer therapy-related problems. ... Table 1: Characteristics of the plants investigated in this study ... of cell viability using MTT (3-(4, 5-.

  17. Novel α, β-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities

    Directory of Open Access Journals (Sweden)

    Yiming Xu

    2017-11-01

    Full Text Available Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, β-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR analysis indicated that introduction of α, β-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.

  18. Polymeric micelles for potentiated antiulcer and anticancer activities of naringin

    Science.gov (United States)

    Mohamed, Elham Abdelmonem; Abu Hashim, Irhan Ibrahim; Yusif, Rehab Mohammad; Shaaban, Ahmed Abdel Aziz; El-Sheakh, Ahmed Ramadan; Hamed, Mohammed Fawzy; Badria, Farid Abd Elreheem

    2018-01-01

    Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin–PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities. PMID:29497294

  19. Role of Dopamine Receptors in the Anticancer Activity of ONC201.

    Science.gov (United States)

    Kline, Christina Leah B; Ralff, Marie D; Lulla, Amriti R; Wagner, Jessica M; Abbosh, Phillip H; Dicker, David T; Allen, Joshua E; El-Deiry, Wafik S

    2018-01-01

    ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201's interaction with DRD2 plays a role in ONC201's anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type-specific manner. On the other hand, DRD3 was generally not detectable. Overexpressing DRD2 in cells with low DRD2 levels increased ONC201-induced PARP cleavage, which was preceded and correlated with an increase in ONC201-induced CHOP mRNA expression. On the other hand, knocking out DRD2 using CRISPR/Cas9 in three cancer cell lines was not sufficient to abrogate ONC201's anticancer effects. Although ONC201's anticancer activity was not dependent on DRD2 expression in the cancer cell types tested, we assessed the cytotoxic potential of DRD2 blockade. Transient DRD2 knockdown in HCT116 cells activated the integrated stress response and reduced cell number. Pharmacological antagonism of DRD2 significantly reduced cell viability. Thus, we demonstrate in this study that disrupting dopamine receptor expression and activity can have cytotoxic effects that may at least be in part due to the activation of the integrated stress response. On the other hand, ONC201's anticancer activity goes beyond its ability to antagonize DRD2, potentially due to ONC201's ability to activate other pathways that are independent of DRD2. Nevertheless, blocking the dopamine D1-like receptor DRD5 via siRNA or the use of a pharmacological antagonist promoted ONC201-induced anticancer activity. Copyright © 2018 The Authors

  20. Role of Dopamine Receptors in the Anticancer Activity of ONC201

    Directory of Open Access Journals (Sweden)

    Christina Leah B. Kline

    2018-01-01

    Full Text Available ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201’s interaction with DRD2 plays a role in ONC201’s anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type–specific manner. On the other hand, DRD3 was generally not detectable. Overexpressing DRD2 in cells with low DRD2 levels increased ONC201-induced PARP cleavage, which was preceded and correlated with an increase in ONC201-induced CHOP mRNA expression. On the other hand, knocking out DRD2 using CRISPR/Cas9 in three cancer cell lines was not sufficient to abrogate ONC201’s anticancer effects. Although ONC201’s anticancer activity was not dependent on DRD2 expression in the cancer cell types tested, we assessed the cytotoxic potential of DRD2 blockade. Transient DRD2 knockdown in HCT116 cells activated the integrated stress response and reduced cell number. Pharmacological antagonism of DRD2 significantly reduced cell viability. Thus, we demonstrate in this study that disrupting dopamine receptor expression and activity can have cytotoxic effects that may at least be in part due to the activation of the integrated stress response. On the other hand, ONC201’s anticancer activity goes beyond its ability to antagonize DRD2, potentially due to ONC201’s ability to activate other pathways that are independent of DRD2. Nevertheless, blocking the dopamine D1-like receptor DRD5 via siRNA or the use of a pharmacological antagonist promoted ONC201-induced anticancer activity.

  1. Anticancer Activity of Indian Stingless Bee Propolis: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Milind K. Choudhari

    2013-01-01

    Full Text Available Indian stingless bee propolis has a complex chemical nature and is reported to possess various medicinal properties. In the present study, anticancer activity of the ethanolic extract of propolis (EEP was explored by testing the cytotoxic and apoptotic effect in four different cancer cell lines, namely, MCF-7 (human breast cancer, HT-29 (human colon adenocarcinoma, Caco-2 (human epithelial colorectal adenocarcinoma, and B16F1 (murine melanoma, at different concentrations. Cytotoxicity was evaluated by MTT assay and Trypan blue dye exclusion assay. EEP at a concentration of 250 g/mL exhibited ≥50% mortality in all cell lines tested (i.e., IC50 value. EEP revealed a concentration and time dependent cytotoxic effect. Apoptosis was estimated by differential staining (ethidium bromide/acridine orange and TUNEL (deoxynucleotidyl transferase-dUTP nick end labeling assay. Light microscopy and atomic force microscopy demonstrated morphological features of apoptosis in all the cell lines after treatment with 250 g/mL EEP for 24 h. Thus, early onset of apoptosis is the reason for anticancer activity of Indian stingless bee propolis. Further, the antioxidant potential of Indian stingless bee propolis was demonstrated to substantiate its anticancer activity.

  2. Shatavarins (containing Shatavarin IV) with anticancer activity from the roots of Asparagus racemosus

    Science.gov (United States)

    Mitra, Shankar K.; Prakash, Neswi S.; Sundaram, Ramachandran

    2012-01-01

    Objectives: The anticancer activity of shatavarins (containing shatavarin IV) isolated from the roots of Asparagus racemosus (Wild) was evaluated using in vitro and in vivo experimental models. Material and Methods: The shatavarin IV was isolated from ethyl acetate insoluble fraction (AR-2B) of chloroform:methanol (2:1) (AR-2) extract of A. racemosus roots. The cytotoxicity (in vitro) of shatavarin IV and other shatavarins rich fraction was carried out using of MTT assay using MCF-7 (human breast cancer), HT-29 (human colon adenocarcinoma), and A-498 (human kidney carcinoma) cell lines. The in vivo anticancer activity of shatavarins (containing shatavarin IV) was evaluated against Ehrlich ascites carcinoma (EAC) tumor bearing mice. Results: The isolated shatavarin IV (84.69 %) along with shatavarins rich fraction, coded AR-2B containing 5.05% shatavarin IV showed potent cytotoxicity. Oral administration of AR-2B to tumor bearing mice at doses of 250 and 500 mg/kg body weight for 10 days, showed significant reduction in percent increase in body weight, tumor volume, packed cell volume, viable tumor cell count, and increased non-viable cell count when compared to the untreated mice of the EAC control group. The restoration of hematological parameters towards normalcy was also observed. Conclusion: The result suggests that the shatavarins (containing shatavarin IV) rich fraction (AR-2B) exhibits significant anticancer activity in both in vitro and in vivo experimental models. PMID:23248403

  3. Synthesis, characterization and anticancer activity of gold(I) complexes that contain tri-tert-butylphosphine and dialkyl dithiocarbamate ligands

    KAUST Repository

    Altaf, Muhammad

    2015-03-10

    Two new gold(I) complexes that contain tri-ter-butylphosphine and dialkyl dithiocarbamate ligands were synthesized and characterized by FTIR, NMR spectroscopy, Cyclic voltammetry, elemental analysis and X-ray diffraction. The in vitro cytotoxicity of both complexes was examined against A549 (lung cancer), MCF7 (breast cancer), and HeLa (cervical cancer) human cancer cell lines. Both complexes exhibit very strong in vitro cytotoxic effects against A549, MCF7 and HeLa cell lines. The screening of the cytotoxic activity based on IC50 data against the A549, MCF7, and HeLa lines shows that the synthesized gold(I) complexes are highly effective, particularly against HeLa cancer cell line. Based on IC50 data, the cytotoxic activity of both complexes is better than well-known commercial anticancer drug cisplatin against all the three cancer lines tested.

  4. Antibacterial, Anticancer and Neuroprotective Activities of Rare Actinobacteria from Mangrove Forest Soils.

    Science.gov (United States)

    Azman, Adzzie-Shazleen; Othman, Iekhsan; Fang, Chee-Mun; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

    2017-06-01

    Mangrove is a complex ecosystem that contains diverse microbial communities, including rare actinobacteria with great potential to produce bioactive compounds. To date, bioactive compounds extracted from mangrove rare actinobacteria have demonstrated diverse biological activities. The discovery of three novel rare actinobacteria by polyphasic approach, namely Microbacterium mangrovi MUSC 115 T , Sinomonas humi MUSC 117 T and Monashia flava MUSC 78 T from mangrove soils at Tanjung Lumpur, Peninsular Malaysia have led to the screening on antibacterial, anticancer and neuroprotective activities. A total of ten different panels of bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, ATCC 70069, Pseudomonas aeruginosa NRBC 112582 and others were selected for antibacterial screening. Three different neuroprotective models (hypoxia, oxidative stress, dementia) were done using SHSY5Y neuronal cells while two human cancer cells lines, namely human colon cancer cell lines (HT-29) and human cervical carcinoma cell lines (Ca Ski) were utilized for anticancer activity. The result revealed that all extracts exhibited bacteriostatic effects on the bacteria tested. On the other hand, the neuroprotective studies demonstrated M. mangrovi MUSC 115 T extract exhibited significant neuroprotective properties in oxidative stress and dementia model while the extract of strain M. flava MUSC 78 T was able to protect the SHSY5Y neuronal cells in hypoxia model. Furthermore, the extracts of M. mangrovi MUSC 115 T and M. flava MUSC 78 T exhibited anticancer effect against Ca Ski cell line. The chemical analysis of the extracts through GC-MS revealed that the majority of the compounds present in all extracts are heterocyclic organic compound that could explain for the observed bioactivities. Therefore, the results obtained in this study suggested that rare actinobacteria discovered from mangrove environment could be potential sources of antibacterial, anticancer and

  5. In vitro anticancer activity of microbial isolates from diverse habitats

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    Angel Treasa Thomas

    2011-06-01

    Full Text Available Extracts from natural products, especially microorganisms, have served as a valuable source of diverse molecules in many drug discovery efforts and led to the discovery of several important drugs. Identification of microbial strains having promising biological activities and purifying the bio-molecules responsible for the activities, have led to the discovery of many bioactive molecules. Extracellular, as well as intracellular, extracts of the metabolites of thirty-six bacterial and twenty-four fungal isolates, grown under unusual conditions such as high temperature, high salt and low sugar concentrations, were in vitro tested for their cytotoxic potential on various cancer cell lines. The extracts were screened on HeLa and MCF-7 cell lines to study the cytotoxic potential. Nuclear staining and flow cytometric studies were carried out to assess the potential of the extracts in arresting the cell cycle. The crude ethylacetate extract of isolate F-21 showed promising results by MTT assay with IC50 as low as 20.37±0.36 µg/mL on HeLa, and 44.75±0.81 µg/mL on MCF-7 cells, comparable with Cisplatin. The isolate F-21 was identified as Aspergillus sp. Promising results were also obtained with B-2C and B-4E strains. Morphological studies, biochemical tests and preliminary chemical investigation of the extracts were also carried out.Extratos de produtos naturais, especialmente de microrganismos, constituíram-se em fonte valiosa de diversas moléculas em muitas descobertas de fármacos e levaram à descoberta de fármacos importantes. A identificação de espécies microbianas que apresentam atividade biológica e a purificação de biomoléculas responsáveis pelas atividades levou à descoberta de muitas moléculas bioativas. Extratos extracelulares tanto quanto intracelulares de metabólitos de 36 isolados de bactérias e 24 isolados de fungos, que cresceram sob condições não usuais, como alta temperatura, alta concentração de sal e baixa

  6. 2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells.

    Science.gov (United States)

    Bauer, Matthias R; Joerger, Andreas C; Fersht, Alan R

    2016-09-06

    The tumor suppressor p53 has the most frequently mutated gene in human cancers. Many of p53's oncogenic mutants are just destabilized and rapidly aggregate, and are targets for stabilization by drugs. We found certain 2-sulfonylpyrimidines, including one named PK11007, to be mild thiol alkylators with anticancer activity in several cell lines, especially those with mutationally compromised p53. PK11007 acted by two routes: p53 dependent and p53 independent. PK11007 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11007 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA. More generally, there was cell death that was independent of p53 but dependent on glutathione depletion and associated with highly elevated levels of reactive oxygen species and induction of endoplasmic reticulum (ER) stress, as also found for the anticancer agent PRIMA-1(MET)(APR-246). PK11007 may be a lead for anticancer drugs that target cells with nonfunctional p53 or impaired reactive oxygen species (ROS) detoxification in a wide variety of mutant p53 cells.

  7. Chemical composition and anticancer, antiinflammatory, antioxidant and antimalarial activities of leaves essential oil of Cedrelopsis grevei.

    Science.gov (United States)

    Afoulous, Samia; Ferhout, Hicham; Raoelison, Emmanuel Guy; Valentin, Alexis; Moukarzel, Béatrice; Couderc, François; Bouajila, Jalloul

    2013-06-01

    The essential oil from Cedrelopsis grevei leaves, an aromatic and medicinal plant from Madagascar, is widely used in folk medicine. Essential oil was characterized by GC-MS and quantified by GC-FID. Sixty-four components were identified. The major constituents were: (E)-β-farnesene (27.61%), δ-cadinene (14.48%), α-copaene (7.65%) and β-elemene (6.96%). The essential oil contained a complex mixture consisting mainly sesquiterpene hydrocarbons (83.42%) and generally sesquiterpenes (98.91%). The essential oil was tested cytotoxic (on human breast cancer cells MCF-7), antimalarial (Plasmodium falciparum), antiinflammatory and antioxidant (ABTS and DPPH assays) activities. C. grevei essential oil was active against MCF-7 cell lines (IC50=21.5 mg/L), against P. falciparum, (IC50=17.5mg/L) and antiinflammatory (IC50=21.33 mg/L). The essential oil exhibited poor antioxidant activity against DPPH (IC50>1000 mg/L) and ABTS (IC50=110 mg/L) assays. A bibliographical review was carried out of all essential oils identified and tested with respect to antiplasmodial, anticancer and antiinflammatory activities. The aim was to establish correlations between the identified compounds and their biological activities (antiplasmodial, anticancer and antiinflammatory). According to the obtained correlations, 1,4-cadinadiene (R(2)=0.61) presented a higher relationship with antimalarial activity. However, only (Z)-β-farnesene (R(2)=0.73) showed a significant correlation for anticancer activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii

    International Nuclear Information System (INIS)

    Le Calve, Benjamin; Lallemand, Benjamin; Perrone, Carmen; Lenglet, Gaelle; Depauw, Sabine; Van Goietsenoven, Gwendoline; Bury, Marina; Vurro, Maurizio; Herphelin, Francoise; Andolfi, Anna; Zonno, Maria Chiara; Mathieu, Veronique; Dufrasne, Francois; Van Antwerpen, Pierre; Poumay, Yves

    2011-01-01

    The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.

  9. Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells.

    Science.gov (United States)

    Cheng, Wan-Li; Huang, Chien-Yu; Tai, Cheng-Jeng; Chang, Yu-Jia; Hung, Chin-Sheng

    2018-02-01

    Androgen deprivation therapy remains the principal treatment for patients with advanced prostate cancer, though, most patients will eventually develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated maspin-induction has been identified in cancer patients. However, the role of maspin on the anticancer activity of curcumin derived from turmeric (Curcuma longa) in HRPC cells has not been elucidated. The anticancer action of curcumin in hormone-independent prostate cancer cells (DU145, and PC-3) was determined by measures of cell survival rate. The cause of maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was evaluated by measures of cell survival rate, cell-cycle distribution, and apoptosis signaling analysis. Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression). RNA interference-mediated maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with control cells. Maspin can enhance the sensitivity of HRPC cells to curcumin treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Synthesis, characterization and anticancer activity of kaempferol-zinc(II) complex.

    Science.gov (United States)

    Tu, Lv-Ying; Pi, Jiang; Jin, Hua; Cai, Ji-Ye; Deng, Sui-Ping

    2016-06-01

    According to the previous studies, the anticancer activity of flavonoids could be enhanced when they are coordinated with transition metal ions. In this work, kaempferol-zinc(II) complex (kaempferol-Zn) was synthesized and its chemical properties were characterized by UV-VIS, FT-IR, (1)H NMR, elemental analysis, electrospray mass spectrometry (ES-MS) and fluorescence spectroscopy, which showed that the synthesized complex was coordinated with a Zn(II) ion via the 3-OH and 4-oxo groups. The anticancer effects of kaempferol-Zn and free kaempferol on human oesophageal cancer cell line (EC9706) were compared. MTT results demonstrated that the killing effect of kaempferol-Zn was two times higher than that of free kaempferol. Atomic force microscopy (AFM) showed the morphological and ultrastructural changes of cellular membrane induced by kaempferol-Zn at subcellular or nanometer level. Moreover, flow cytometric analysis indicated that kaempferol-Zn could induce apoptosis in EC9706 cells by regulating intracellular calcium ions. Collectively, all the data showed that kaempferol-Zn might be served as a kind of potential anticancer agent. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Anticancer activity of a novel small molecule tubulin inhibitor STK899704.

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    Krisada Sakchaisri

    Full Text Available We have identified the small molecule STK899704 as a structurally novel tubulin inhibitor. STK899704 suppressed the proliferation of cancer cell lines from various origins with IC50 values ranging from 0.2 to 1.0 μM. STK899704 prevented the polymerization of purified tubulin in vitro and also depolymerized microtubule in cultured cells leading to mitotic arrest, associated with increased Cdc25C phosphorylation and the accumulation of both cyclin B1 and polo-like kinase 1 (Plk1, and apoptosis. Unlike many anticancer drugs such as Taxol and doxorubicin, STK899704 effectively displayed antiproliferative activity against multidrug-resistant cancer cell lines. The proposed binding mode of STK899704 is at the interface between αβ-tubulin heterodimer overlapping with the colchicine-binding site. Our in vivo carcinogenesis model further showed that STK 899704 is potent in both the prevention and regression of tumors, remarkably reducing the number and volume of skin tumor by STK899704 treatment. Moreover, it was significant to note that the efficacy of STK899704 was surprisingly comparable to 5-fluorouracil, a widely used anticancer therapeutic. Thus, our results demonstrate the potential of STK899704 to be developed as an anticancer chemotherapeutic and an alternative candidate for existing therapies.

  12. Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells.

    Science.gov (United States)

    Potikanond, Saranyapin; Sookkhee, Siriwoot; Na Takuathung, Mingkwan; Mungkornasawakul, Pitchaya; Wikan, Nitwara; Smith, Duncan R; Nimlamool, Wutigri

    2017-01-01

    Kaempferia parviflora (KP) has been traditionally used as a folk remedy to treat several diseases including cancer, and several studies have reported cytotoxic activities of extracts of KP against a number of different cancer cell lines. However, many aspects of the molecular mechanism of action of KP remain unclear. In particular, the ability of KP to regulate cancer cell growth and survival signaling is still largely unexplored. The current study aimed to investigate the effects of KP on cell viability, cell migration, cell invasion, cell apoptosis, and on signaling pathways related to growth and survival of cervical cancer cells, HeLa. We discovered that KP reduced HeLa cell viability in a concentration-dependent manner. The potent cytotoxicity of KP against HeLa cells was associated with a dose-dependent induction of apoptotic cell death as determined by flow cytometry and observation of nuclear fragmentation. Moreover, KP-induced cell apoptosis was likely to be mediated through the intrinsic apoptosis pathway since caspase 9 and caspase 7, but not BID, were shown to be activated after KP exposure. Based on the observation that KP induced apoptosis in HeLa cell, we further investigated the effects of KP at non-cytotoxic concentrations on suppressing signal transduction pathways relevant to cell growth and survival. We found that KP suppressed the MAPK and PI3K/AKT signaling pathways in cells activated with EGF, as observed by a significant decrease in phosphorylation of ERK1/2, Elk1, PI3K, and AKT. The data suggest that KP interferes with the growth and survival of HeLa cells. Consistent with the inhibitory effect on EGF-stimulated signaling, KP potently suppressed the migration of HeLa cells. Concomitantly, KP was demonstrated to markedly inhibit HeLa cell invasion. The ability of KP in suppressing the migration and invasion of HeLa cells was associated with the suppression of matrix metalloproteinase-2 production. These data strongly suggest that KP may slow

  13. Novel molecular, cytotoxical, and immunological study on promising and selective anticancer activity of Mung bean sprouts

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    Hafidh Rand R

    2012-11-01

    Full Text Available Abstract Background The anticancer and immunomodulatory activity of mung bean sprouts (MBS and the underlying mechanisms against human cervical and hepatocarcinoma cancer cells were explored. Methods MBS cytotoxicity and MBS-induced anticancer cytokines, TNF-α and IFN-β from cancer cells, and immunological cytokines, IL-4, IFN-γ, and IL-10 from peripheral mononuclear cells (PMNC were assessed by MTS and ELISA assays. Apoptotic cells were investigated by flow cytometry. The expression level of apoptotic genes (Bax, BCL-2, Capsases 7–9 and cell cycle regulatory genes (cyclin D, E, and A and tumor suppressor proteins (p27, p21, and p53 was assessed by real-time qPCR in the cancer cells treated with extract IC50. Results The cytotoxicity on normal human cells was significantly different from HeLa and HepG2 cells, 163.97 ± 5.73, 13.3 ± 0.89, and 14.04 ± 1.5 mg/ml, respectively. The selectivity index (SI was 12.44 ± 0.83 for HeLa and 11.94 ± 1.2 for HepG2 cells. Increased levels of TNF-α and IFN-β were observed in the treated HeLa and HepG2 culture supernatants when compared with untreated cells. MBS extract was shown to be an immunopolarizing agent by inducing IFNγ and inhibiting IL-4 production by PBMC; this leads to triggering of CMI and cellular cytotoxicity. The extract induced apoptosis, in a dose and time dependent manner, in treated HeLa and HepG2, but not in untreated, cells (P Conclusion MBS extract was shown to be a potent anticancer agent granting new prospects of anticancer therapy using natural products.

  14. Anticancer activity of Pupalia lappacea on chronic myeloid leukemia K562 cells.

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    Ravi, Alvala; Alvala, Mallika; Sama, Venkatesh; Kalle, Arunasree M; Irlapati, Vamshi K; Reddy, B Madhava

    2012-12-05

    Cancer is one of the most prominent human diseases which has enthused scientific and commercial interest in the discovery of newer anticancer agents from natural sources. Here we demonstrated the anticancer activity of ethanolic extract of aerial parts of Pupalia lappacea (L) Juss (Amaranthaceae) (EAPL) on Chronic Myeloid Leukemia K562 cells. Antiproliferative activity of EAPL was determined by MTT assay using carvacrol as a positive control. Induction of apoptosis was studied by annexin V, mitochondrial membrane potential, caspase activation and cell cycle analysis using flow cytometer and modulation in protein levels of p53, PCNA, Bax and Bcl2 ratio, cytochrome c and cleavage of PARP were studied by Western blot analysis. The standardization of the extract was performed through reverse phase-HPLC using Rutin as biomarker. The results showed dose dependent decrease in growth of K562 cells with an IC50 of 40 ± 0.01 μg/ml by EAPL. Induction of apoptosis by EAPL was dose dependent with the activation of p53, inhibition of PCNA, decrease in Bcl2/Bax ratio, decrease in the mitochondrial membrane potential resulting in release of cytochrome c, activation of multicaspase and cleavage of PARP. Further HPLC standardization of EAPL showed presence 0.024% of Rutin. Present study significantly demonstrates anticancer activity of EAPL on Chronic Myeloid Leukemia (K562) cells which can lead to potential therapeutic agent in treating cancer. Rutin, a known anti cancer compound is being reported and quantified for the first time from EAPL.

  15. Effect of Cellular Location of Human Carboxylesterase 2 on CPT-11 Hydrolysis and Anticancer Activity.

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    Yuan-Ting Hsieh

    Full Text Available CPT-11 is an anticancer prodrug that is clinically used for the treatment of metastatic colorectal cancer. Hydrolysis of CPT-11 by human carboxylesterase 2 (CE2 generates SN-38, a topoisomerase I inhibitor that is the active anti-tumor agent. Expression of CE2 in cancer cells is under investigation for the tumor-localized activation of CPT-11. CE2 is normally expressed in the endoplasmic reticulum of cells but can be engineered to direct expression of active enzyme on the plasma membrane or as a secreted form. Although previous studies have investigated different locations of CE2 expression in cancer cells, it remains unclear if CE2 cellular location affects CPT-11 anticancer activity. In the present study, we directly compared the influence of CE2 cellular location on substrate hydrolysis and CPT-11 cytotoxicity. We linked expression of CE2 and enhanced green fluorescence protein (eGFP via a foot-and-mouth disease virus 2A (F2A peptide to facilitate fluorescence-activated cell sorting to achieve similar expression levels of ER-located, secreted or membrane-anchored CE2. Soluble CE2 was detected in the medium of cells that expressed secreted and membrane-anchored CE2, but not in cells that expressed ER-retained CE2. Cancer cells that expressed all three forms of CE2 were more sensitive to CPT-11 as compared to unmodified cancer cells, but the membrane-anchored and ER-retained forms of CE2 were consistently more effective than secreted CE2. We conclude that expression of CE2 in the ER or on the membrane of cancer cells is suitable for enhancing CPT-11 anticancer activity.

  16. Influence of the π-coordinated arene on the anticancer activity of ruthenium(II carbohydrate organometallic complexes

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    Muhammad eHanif

    2013-10-01

    Full Text Available The synthesis and in vitro cytotoxicity of a series of RuII(arene complexes with carbohydrate-derived phosphite ligands and various arene co-ligands is described. The arene ligand has a strong influence on the in vitro anticancer activity of this series of compounds, which correlates fairly well with cellular accumulation. The most lipophilic compound bearing a biphenyl moiety and a cyclohexylidene-protected carbohydrate is the most cytotoxic with unprecedented IC50 values for the compound class in three human cancer cell lines. This compound shows reactivity to the DNA model nucleobase 9-ethylguanine, but does not alter the secondary structure of plasmid DNA indicating that other biological targets are responsible for its cytotoxic effect.

  17. Pharmacological evaluation for anticancer and immune activities of a novel polysaccharide isolated from Boletus speciosus Frost.

    Science.gov (United States)

    Hou, Yiling; Ding, Xiang; Hou, Wanru; Song, Bo; Wang, Ting; Wang, Fang; Li, Jian; Zeng, Yichun; Zhong, Jie; Xu, Ting; Zhu, Hongqing

    2014-04-01

    The fungal polysaccharides have been revealed to exhibit a variety of biological activities, including antitumor, immune-stimulation and antioxidation activities. In the present study, the immune and anticancer activities of a novel polysaccharide, BSF-A, isolated from Boletus speciosus Frost was investigated. The inhibitory rate of S180 tumors in mice treated with 40 mg/kg BSF-A reached 62.449%, which was the highest rate from the three doses administered; this may be comparable to mannatide. The antitumor activity of BSF-A is commonly considered to be a consequence of the stimulation of the cell-mediated immune response, as it may significantly promote the macrophage cells in the dose range of 100-400 µg/ml in vitro. The levels of the cytokines, IL-6, IL-1β and TNF-α, and nitric oxide, induced by BSF-A treatment at varying concentrations in the macrophage cells were similar to the levels in the cells treated with lipopolysaccharide. There was weak expression of the TNF-α, IL-6, IL-1β and inducible nitric oxide synthase mRNA in the untreated macrophages, but this increased significantly in a dose-dependent manner in the BSF-A-treated cells. BSF-A also had a time- and dose-dependent effect on the growth inhibition of the Hep-2 cells, with the concentration of 400 µg/ml having the highest inhibitory rate. A quantitative PCR array analysis of the gene expression profiles indicated that BSF-A had anticancer activities that affected cell apoptosis in the Hep-2 cells. The results obtained in the present study indicated that the purified polysaccharide of Boletus speciosus Frost is a potential source of natural anticancer substances.

  18. Bauhinia variegata leaf extracts exhibit considerable antibacterial, antioxidant, and anticancer activities.

    Science.gov (United States)

    Mishra, Amita; Sharma, Amit Kumar; Kumar, Shashank; Saxena, Ajit K; Pandey, Abhay K

    2013-01-01

    The present study reports the phytochemical profiling, antimicrobial, antioxidant, and anticancer activities of Bauhinia variegata leaf extracts. The reducing sugar, anthraquinone, and saponins were observed in polar extracts, while terpenoids and alkaloids were present in nonpolar and ethanol extracts. Total flavonoid contents in various extracts were found in the range of 11-222.67 mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions exhibited considerable inhibition against Klebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains of E. coli, Proteus spp. and Pseudomonas spp. Minimum bactericidal concentration (MBC) values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest MBC (3.5 mg/mL) was recorded for ethanol extract against Pseudomonas spp. The antioxidant activity of the extracts was compared with standard antioxidants. Dose dependent response was observed in reducing power of extracts. Polar extracts demonstrated appreciable metal ion chelating activity at lower concentrations (10-40 μg/mL). Many extracts showed significant antioxidant response in beta carotene bleaching assay. AQ fraction of B. variegata showed pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1 human cancer cell lines with 90-99% cell growth inhibitory activity. Ethyl acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1 cell lines. The study demonstrates notable antibacterial, antioxidant, and anticancer activities in B. variegata leaf extracts.

  19. Bauhinia variegata Leaf Extracts Exhibit Considerable Antibacterial, Antioxidant, and Anticancer Activities

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    Amita Mishra

    2013-01-01

    Full Text Available The present study reports the phytochemical profiling, antimicrobial, antioxidant, and anticancer activities of Bauhinia variegata leaf extracts. The reducing sugar, anthraquinone, and saponins were observed in polar extracts, while terpenoids and alkaloids were present in nonpolar and ethanol extracts. Total flavonoid contents in various extracts were found in the range of 11–222.67 mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions exhibited considerable inhibition against Klebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains of E. coli, Proteus spp. and Pseudomonas spp. Minimum bactericidal concentration (MBC values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest MBC (3.5 mg/mL was recorded for ethanol extract against Pseudomonas spp. The antioxidant activity of the extracts was compared with standard antioxidants. Dose dependent response was observed in reducing power of extracts. Polar extracts demonstrated appreciable metal ion chelating activity at lower concentrations (10–40 μg/mL. Many extracts showed significant antioxidant response in beta carotene bleaching assay. AQ fraction of B. variegata showed pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1 human cancer cell lines with 90–99% cell growth inhibitory activity. Ethyl acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1 cell lines. The study demonstrates notable antibacterial, antioxidant, and anticancer activities in B. variegata leaf extracts.

  20. In vitro antioxidant and anticancer activity of young Zingiber officinale against human breast carcinoma cell lines

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    Iqbal Asif

    2011-09-01

    Full Text Available Abstract Background Ginger is one of the most important spice crops and traditionally has been used as medicinal plant in Bangladesh. The present work is aimed to find out antioxidant and anticancer activities of two Bangladeshi ginger varieties (Fulbaria and Syedpuri at young age grown under ambient (400 μmol/mol and elevated (800 μmol/mol CO2 concentrations against two human breast cancer cell lines (MCF-7 and MDA-MB-231. Methods The effects of ginger on MCF-7 and MDA-MB-231 cell lines were determined using TBA (thiobarbituric acid and MTT [3-(4,5-dimethylthiazolyl-2,5-diphenyl-tetrazolium bromide] assays. Reversed-phase HPLC was used to assay flavonoids composition among Fulbaria and Syedpuri ginger varieties grown under increasing CO2 concentration from 400 to 800 μmol/mol. Results Antioxidant activities in both varieties found increased significantly (P ≤ 0.05 with increasing CO2 concentration from 400 to 800 μmol/mol. High antioxidant activities were observed in the rhizomes of Syedpuri grown under elevated CO2 concentration. The results showed that enriched ginger extract (rhizomes exhibited the highest anticancer activity on MCF-7 cancer cells with IC50 values of 34.8 and 25.7 μg/ml for Fulbaria and Syedpuri respectively. IC50 values for MDA-MB-231 exhibition were 32.53 and 30.20 μg/ml for rhizomes extract of Fulbaria and Syedpuri accordingly. Conclusions Fulbaria and Syedpuri possess antioxidant and anticancer properties especially when grown under elevated CO2 concentration. The use of ginger grown under elevated CO2 concentration may have potential in the treatment and prevention of cancer.

  1. Design and synthesis of novel C14-urea-tetrandrine derivatives with potent anti-cancer activity.

    Science.gov (United States)

    Lan, Junjie; Huang, Lan; Lou, Huayong; Chen, Chao; Liu, Tangjingjun; Hu, Shengcao; Yao, Yao; Song, Junrong; Luo, Jun; Liu, Yazhou; Xia, Bin; Xia, Lei; Zeng, Xueyi; Ben-David, Yaacov; Pan, Weidong

    2018-01-01

    Tetrandrine is a dibenzyltetrahydroisoquinoline alkaloid, isolated from traditional Chinese medicinal plant Stephania tetrandra, with anti-tumor activity. Our previous study identified several derivatives of tetrandrine showing better activities than parental compound against human hepatocellular carcinoma cells. To increase diversity and cytotoxic activities of the original compound, a series of novel 14-urea-tetrandrine derivatives were synthesized through structural modification of tetrandrine. These derivaties demonstrated a moderate to strong anti-proliferative activities against human cell lines HEL and K562 (Leukemia), prostate (PC3), breast (MDA-MB-231) and melanoma (WM9). Compound 4g showed strongest cytotoxic effect against PC3 cells with IC 50 value of 0.64 μM, which was 12-fold, 31-fold and 26-fold lower than the parental tetrandrine, 5-fluorouracil and cisplatin, respectively. Preliminary structure-activity relationship study indicated that urea subsititution was the key pharmacophore for the enhancement of their antitumor activities. Induction of apoprosis by 4g was associated with the activation of pro-apoptotic protein BAX and inhibition of antiapoptosis proteins survivin as well as Bcl-2. Moreover, activation of caspases led to increase cleavage of PARP, which further accelerates apoptotic cell death. These results reveal that the compound 4g may be used as a potential anticancer drug candidate. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Impediments to Enhancement of CPT-11 Anticancer Activity by E. coli Directed Beta-Glucuronidase Therapy

    Science.gov (United States)

    Hsieh, Yuan-Ting; Chen, Kai-Chuan; Cheng, Chiu-Min; Cheng, Tian-Lu; Tao, Mi-Hua; Roffler, Steve R.

    2015-01-01

    CPT-11 is a camptothecin analog used for the clinical treatment of colorectal adenocarcinoma. CPT-11 is converted into the therapeutic anti-cancer agent SN-38 by liver enzymes and can be further metabolized to a non-toxic glucuronide SN-38G, resulting in low SN-38 but high SN-38G concentrations in the circulation. We previously demonstrated that adenoviral expression of membrane-anchored beta-glucuronidase could promote conversion of SN-38G to SN-38 in tumors and increase the anticancer activity of CPT-11. Here, we identified impediments to effective tumor therapy with E. coli that were engineered to constitutively express highly active E. coli beta-glucuronidase intracellularly to enhance the anticancer activity of CPT-11. The engineered bacteria, E. coli (lux/βG), could hydrolyze SN-38G to SN-38, increased the sensitivity of cultured tumor cells to SN-38G by about 100 fold and selectively accumulated in tumors. However, E. coli (lux/βG) did not more effectively increase CPT-11 anticancer activity in human tumor xenografts as compared to non-engineered E. coli. SN-38G conversion to SN-38 by E. coli (lux/βG) appeared to be limited by slow uptake into bacteria as well as by segregation of E. coli in necrotic regions of tumors that may be relatively inaccessible to systemically-administered drug molecules. Studies using a fluorescent glucuronide probe showed that significantly greater glucuronide hydrolysis could be achieved in mice pretreated with E. coli (lux/βG) by direct intratumoral injection of the glucuronide probe or by intratumoral lysis of bacteria to release intracellular beta-glucuronidase. Our study suggests that the distribution of beta-glucuronidase, and possibly other therapeutic proteins, in the tumor microenvironment might be an important barrier for effective bacterial-based tumor therapy. Expression of secreted therapeutic proteins or induction of therapeutic protein release from bacteria might therefore be a promising strategy to enhance anti

  3. In Vitro Anticancer Activity of a Nonpolar Fraction from Gynostemma pentaphyllum (Thunb. Makino

    Directory of Open Access Journals (Sweden)

    Yantao Li

    2016-01-01

    Full Text Available Gynostemma pentaphyllum (Thunb. Makino (GpM has been widely used in traditional Chinese medicine (TCM for the treatment of various diseases including cancer. Most previous studies have focused primarily on polar fractions of GpM for anticancer activities. In this study, a nonpolar fraction EA1.3A from GpM showed potent growth inhibitory activities against four cancer cell lines with IC50 ranging from 31.62 μg/mL to 38.02 μg/mL. Furthermore, EA1.3A also inhibited the growth of breast cancer cell MDA-MB-453 time-dependently, as well as its colony formation ability. EA1.3A induced apoptosis on MDA-MB-453 cells both dose-dependently and time-dependently as analyzed by flow cytometry and verified by western blotting analysis of apoptosis marker cleaved nuclear poly(ADP-ribose polymerase (cPARP. Additionally, EA1.3A induced cell cycle arrest in G0/G1 phase. Chemical components analysis of EA1.3A by GC-MS revealed that this nonpolar fraction from GpM contains 10 compounds including four alkaloids, three organic esters, two terpenes, and one catechol substance, and all these compounds have not been reported in GpM. In summary, the nonpolar fraction EA1.3A from GpM inhibited cancer cell growth through induction of apoptosis and regulation of cell cycle progression. Our study shed light on new chemical bases for the anticancer activities of GpM and feasibilities to develop new anticancer agents from this widely used medicinal plant.

  4. NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

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    Wei-Jan Huang

    2012-01-01

    Full Text Available HDAC inhibitors (HDACis have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP, and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231 and rat glioma cells (C6, with an IC50 ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1, gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21(Waf1/Cip1 gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo.

  5. Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells

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    Xu De Wang

    2018-04-01

    Full Text Available Background: AD-2 (20(R-dammarane-3b, 12b, 20, 25-tetrol; 25-OH-PPD is a ginsenoside and isolated from Panax ginseng, showing anticancer activity against extensive human cancer cell lines. In this study, effects and mechanisms of 1C ((20R-3b-O-(L-alanyl-dammarane-12b, 20, 25-triol, a modified version of AD-2, were evaluated for its development as a novel anticancer drug. Methods: MTT assay was performed to evaluate cell cytotoxic activity. Cell cycle and levels of reactive oxygen species (ROS were determined using flow cytometry analysis. Western blotting was employed to analyze signaling pathways. Results: 1C concentration-dependently reduces prostate cancer cell viability without affecting normal human gastric epithelial cell line-1 viability. In LNCaP prostate cancer cells, 1C triggered apoptosis via Bcl-2 family-mediated mitochondria pathway, downregulated expression of mouse double minute 2, upregulated expression of p53 and stimulated ROS production. ROS scavenger, N-acetylcysteine, can attenuate 1C-induced apoptosis. 1C also inhibited the proliferation of LNCaP cells through inhibition on Wnt/β-catenin signaling pathway. Conclusion: 1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 family-mediated mitochondria pathway and ROS production, inhibiting Wnt/β-catenin signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy. Keywords: 1C, AD-2, apoptosis, reactive oxygen species, Wnt/β-catenin pathway

  6. Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation.

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    Emma M Brown

    Full Text Available Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0-50 µg/ml gallic acid equivalents, the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer.

  7. Novel Platinum (Pt)-Vandetanib Hybrid Compounds: Design, Synthesis and Investigation of Anti-cancer Activity and Mechanism of Action

    Science.gov (United States)

    Fei, Rong

    Purpose: Lung cancer is one of the most common cancers and non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancers. 70% of individuals with NSCLC harboring somatic mutations in exons of the epidermal growth factor receptor (EGFR) gene that encode tyrosine kinase domain. EGFR tyrosine kinase inhibitors (TKIs) are promising molecular targeted therapy for NSCLC with sensitizing EGFR mutations. However, secondary mutation of EGFR after treatment of TKIs develops resistance. Vandetanib is introduced to overcome erlotinib resistance as a multi-targeted TKI. However, its anticancer effect is still compromised by EGFR T790M mutation. Therefore, new molecular anticancer strategies are necessarily needed. In this study, vandetanib is incorporated with Pt-based anticancer agents as hybrid compounds, aiming to circumvent TKI resistance. Furthermore, hybrid compounds are investigated in cisplatin resistant problem to expect to overcome resistance by introduction of vandetanib. Methods: Three novel Pt-vandetanib hybrid compounds were synthesized and its physicochemical properties were characterized. Anticancer activity and cytotoxicity were evaluated by sulforhodamine B assay and lactate dehydrogenase release. Docking simulation was performed to investigate the interaction of compounds with EGFR harboring different mutations. Inhibition efficacy of hybrids to kinases was evaluated by kinase inhibition profiling service and cell-free kinase inhibition assay. Mechanistic studies on cytotoxicity activity of the hybrid compounds were carried out. DNA damage response of hybrid compounds was further investigated in KB cells. The cytotoxicity of hybrids was tested in cisplatin resistant KB CP20 cells. Mechanistic of anticancer activity was studied to test inhibition on oncoprotein CIP2Aand DNA damage. Results: Platinum-vandetanib hybrid compounds were synthesized and test to be stable under extracellular condition. Hybrids reacted with 5'-GMP2- and glutathione, and both

  8. Holotransferrin enhances selective anticancer activity of artemisinin against human hepatocellular carcinoma cells.

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    Deng, Xiao-rong; Liu, Zhao-xia; Liu, Feng; Pan, Lei; Yu, He-ping; Jiang, Jin-ping; Zhang, Jian-jun; Liu, Li; Yu, Jun

    2013-12-01

    Artemisinin, also termed qinghaosu, is extracted from the traditional Chinese medicine artemesia annua L. (the blue-green herb) in the early 1970s, which has been confirmed for effectively treating malaria. Additionally, emerging data prove that artemisinin exhibits anti-cancer effects against many types of cancers such as leukemia, melanoma, etc. Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is high in cancer cells, artemisinin and its analogs selectively kill cancer cells with increased intracellular iron concentrations. This study is aimed to investigate the selective inhibitory effects of artemisinin on SMMC-7721 cells in vitro and determine the effect of holotransferrin, which increases the concentration of ferrous iron in cancer cells, combined with artemisinin on the anticancer activity. MTT assay was used for assessing the proliferation of SMMC-7721 cells treated with artemisinin. The induction of apoptosis and inhibition of colony formation in SMMC-7721 cells treated with artemisinin were determined by TdT-mediated dUTP nick end labeling (TUNEL) and colony formation assay, respectively. The results showed that artemisinin at various concentrations significantly inhibited growth, colony formation and cell viability of SMMC-7721 cells (P<0.05), likely due to induction of apoptosis of SMMC-7721 cells. Of interest, it was found that incubation of artemisinin combined with holotransferrin sensitized the growth inhibitory effect of artemisinin on SMMC-7721 cells (P<0.01). Our data suggest that treatment with artemisinin leads to inhibition of viability and proliferation, and apoptosis of SMMC-7721 cells. Furthermore, we observed that holotransferrin significantly enhanced the anti-cancer activity of artemisinin. This study may provide a potential therapeutic choice for liver cancer.

  9. In vitro anti-inflammatory and anti-cancer activities of Cuscuta reflexa Roxb.

    Science.gov (United States)

    Suresh, V; Sruthi, V; Padmaja, B; Asha, V V

    2011-04-12

    To determine anti-inflammatory and anti-cancer activities of Cuscuta reflexa in cell lines (in vitro). Anti-inflammatory activity of the water extract was analysed in vitro using lipopolysaccharide (LPS) induced inflammatory reactions in murine macrophage cell line RAW264.7. The expression of COX-2 and TNF-α genes involved in inflammation was analysed by SQ RT-PCR. EMSA was conducted to analyse the influence of the extract on NF-κB signalling. Anti-cancer activity was analysed on Hep3B cells by MTT assay, DAPI staining, annexin V staining and SQ-RT PCR analysis of BAX, Bcl-2, p53 and survivin. The extract down regulated LPS induced over expression of TNF-α and COX-2 in RAW264.7 cells; blocked NF-κB binding to its motifs and induced apoptosis in Hep3B cells as evidenced from MTT, DAPI staining and annexin V staining assays. The extract up regulated pro-apoptotic factors BAX and p53, and down regulated anti-apoptotic factors Bcl-2 and survivin. The study showed that Cuscuta reflexa inhibits LPS induced inflammatory responses in RAW264.7 cells through interplay of TNF-α, COX-2 and NF-κB signalling. It induced apoptosis in Hep3B cells through the up regulation of p53, BAX and down regulation of Bcl-2 and survivin. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility.

    Science.gov (United States)

    Muhammad, Zarmina; Raza, Abida; Ghafoor, Sana; Naeem, Ayesha; Naz, Syeda Sohaila; Riaz, Sundus; Ahmed, Wajiha; Rana, Nosheen Fatima

    2016-08-25

    Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Anticancer activity of 7-epiclusianone, a benzophenone from Garcinia brasiliensis, in glioblastoma.

    Science.gov (United States)

    Sales, Leilane; Pezuk, Julia Alejandra; Borges, Kleiton Silva; Brassesco, María Sol; Scrideli, Carlos Alberto; Tone, Luiz Gonzaga; dos Santos, Marcelo Henrique; Ionta, Marisa; de Oliveira, Jaqueline Carvalho

    2015-10-30

    Glioblastoma is the most common tumor of the central nervous system and one of the hardest tumors to treat. Consequently, the search for novel therapeutic options is imperative. 7-epiclusianone, a tetraprenylated benzophenone isolated from the epicarp of the native plant Garcinia brasiliensis, exhibits a range of biological activities but its prospect anticancer activity is underexplored. Thus, the aim of the present study was to evaluate the influence of 7-epiclusianone on proliferation, clonogenic capacity, cell cycle progression and induction of apoptosis in two glioblastoma cell lines (U251MG and U138MG). Cell viability was measured by the MTS assay; for the clonogenic assay, colonies were stained with Giemsa and counted by direct visual inspection; For cell cycle analysis, cells were stained with propidium iodide and analyzed by cytometry; Cyclin A expression was determined by immunoblotting; Apoptotic cell death was determined by annexin V fluorescein isothiocyanate labeling and Caspase-3 activity in living cells. Viability of both cell lines was drastically inhibited; moreover, the colony formation capacity was significantly reduced, demonstrating long-term effects even after removal of the drug. 7-epiclusianone treatment at low concentrations also altered cell cycle progression, decreased the S and G2/M populations and at higher concentrations increased the number of cells at sub-G1, in concordance with the increase of apoptotic cells. The present study demonstrates for the first time the anticancer potential of 7-epiclusianone against glioblastoma cells, thus meriting its further investigation as a potential therapeutic agent.

  12. Bioactivity screening of microalgae for antioxidant, anti-inflammatory, anticancer, anti-diabetes and antibacterial activities

    Directory of Open Access Journals (Sweden)

    Chiara eLauritano

    2016-05-01

    Full Text Available Marine microalgae are considered a potentially new and valuable source of biologically active molecules for applications in the food industry as well as in the pharmaceutical, nutraceutical and cosmetic sectors. They can be easily cultured, have short generation times and enable an environmentally-friendly approach to drug discovery by overcoming problems associated with the over-utilization of marine resources and the use of destructive collection practices. In this study, 21 diatoms, 7 dinoflagellates and 4 flagellate species were grown in three different culturing conditions and the corresponding extracts were tested for possible antioxidant, anti-inflammatory, anticancer, anti-diabetes, antibacterial and anti-biofilm activities. In addition, for two diatoms we also tested two different clones to disclose diversity in clone bioactivity. Six diatom species displayed specific anti-inflammatory, anticancer (blocking human melanoma cell proliferation and anti-biofilm (against the bacteria Staphylococcus epidermidis activities whereas, none of the other microalgae were bioactive against the conditions tested for. Furthermore, none of the 6 diatom species tested were toxic on normal human cells. Culturing conditions (i.e. nutrient starvation conditions greatly influenced bioactivity of the majority of the clones/species tested. This study denotes the potential of diatoms as sources of promising bioactives for the treatment of human pathologies.

  13. Low-intensity continuous ultrasound triggers effective bisphosphonate anticancer activity in breast cancer.

    Science.gov (United States)

    Tardoski, Sophie; Ngo, Jacqueline; Gineyts, Evelyne; Roux, Jean-Paul; Clézardin, Philippe; Melodelima, David

    2015-11-18

    Ultrasound (US) is a non-ionizing pressure wave that can produce mechanical and thermal effects. Bisphosphonates have demonstrated clinical utility in bone metastases treatment. Preclinical studies suggest that bisphosphonates have anticancer activity. However, bisphosphonates exhibit a high affinity for bone mineral, which reduces their bioavailability for tumor cells. Ultrasound has been shown to be effective for drug delivery but in interaction with gas bubbles or encapsulated drugs. We examined the effects of a clinically relevant dose of bisphosphonate zoledronate (ZOL) in combination with US. In a bone metastasis model, mice treated with ZOL+US had osteolytic lesions that were 58% smaller than those of ZOL-treated animals as well as a reduced skeletal tumor burden. In a model of primary tumors, ZOL+US treatment reduced by 42% the tumor volume, compared with ZOL-treated animals. Using a fluorescent bisphosphonate, we demonstrated that US forced the release of bisphosphonate from the bone surface, enabling a continuous impregnation of the bone marrow. Additionally, US forced the penetration of ZOL within tumors, as demonstrated by the intratumoral accumulation of unprenylated Rap1A, a surrogate marker of ZOL antitumor activity. Our findings made US a promising modality to trigger bisphosphonate anticancer activity in bone metastases and in primary tumors.

  14. In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells

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    Hyun Ji Eo

    2016-03-01

    Full Text Available Phlorofucofuroeckol A (PFF-A, one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3 has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB, located between positions −147 and −85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK, glycogen synthase kinase (GSK 3β, and IκB kinase (IKK-α blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose polymerase (PARP by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells.

  15. Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning

    International Nuclear Information System (INIS)

    Huang, C.-P.; Fang, W.-H.; Lin, L.-I.; Chiou, Robin Y.; Kan, L.-S.; Chi, N.-H.; Chen, Y.-R.; Lin, T.-Y.; Lin, S.-B.

    2008-01-01

    Cytotoxic alkyl hydroquinone compounds have been isolated from many plants. We previously isolated 3 structurally similar cytotoxic alkyl hydroquinone compounds from the sap of the lacquer tree Rhus succedanea L. belonging to the sumac family, which have a long history of medicinal use in Asia. Each has an unsaturated alkyl chain attached to the 2-position of a hydroquinone ring. One of these isolates, 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)], being the most cytotoxic, was chosen for studying the anticancer mechanism of these compounds. We found that HQ17(3) was a topoisomerase (Topo) II poison. It irreversibly inhibited Topo IIα activity through the accumulation of Topo II-DNA cleavable complexes. A cell-based assay showed that HQ17(3) inhibited the growth of leukemia HL-60 cells with an EC 50 of 0.9 μM, inhibited the topoisomerase-II-deficient cells HL-60/MX2 with an EC 50 of 9.6 μM, and exerted no effect on peripheral blood mononuclear cells at concentrations up to 50 μM. These results suggest that Topo II is the cellular drug target. In HL-60 cells, HQ17(3) promptly inhibited DNA synthesis, induced chromosomal breakage, and led to cell death with an EC 50 about one-tenth that of hydroquinone. Pretreatment of the cells with N-acetylcysteine could not attenuate the cytotoxicity and DNA damage induced by HQ17(3). However, N-acetylcysteine did significantly reduce the cytotoxicity of hydroquinone. In F344 rats, intraperitoneal injection of HQ17(3) for 28 days induced no clinical signs of toxicity. These results indicated that HQ17(3) is a potential anticancer agent, and its structural features could be a model for anticancer drug design

  16. Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

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    Alessandra Mirtes Marques Neves Gonçalves

    2014-07-01

    Full Text Available Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.

  17. Thiolated pectin-doxorubicin conjugates: Synthesis, characterization and anticancer activity studies.

    Science.gov (United States)

    Cheewatanakornkool, Kamonrak; Niratisai, Sathit; Manchun, Somkamol; Dass, Crispin R; Sriamornsak, Pornsak

    2017-10-15

    In this paper, pectin was cross-linked by a coupling reaction with either thioglycolic acid or cystamine dihydrochloride to form thiolated pectins. The thiolated pectins were then coupled with doxorubicin (DOX) derivative to obtain thiolated pectin-DOX conjugates by two different methods, disulfide bond formation and disulfide bond exchange. The disulfide bond exchange method provided a simple, fast, and efficient approach for synthesis of thiolated pectin-DOX conjugates, compared to the disulfide bond formation. Characteristics, physicochemical properties, and morphology of thiolated pectins and thiolated pectin-DOX conjugates were determined. DOX content in thiolated pectin-DOX conjugates using low methoxy pectin was found to be higher than that using high methoxy pectin. The in vitro anticancer activity of thiolated pectin-DOX conjugates was significantly higher than that of free DOX, in mouse colon carcinoma and human bone osteosarcoma cells, but insignificantly different from that of free DOX, in human prostate cancer cells. Due to their promising anticancer activity in mouse colon carcinoma cells, the thiolated pectin-DOX conjugates might be suitable for building drug platform for colorectal cancer-targeted delivery of DOX. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    International Nuclear Information System (INIS)

    Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan; Zheng Lan; Zhao Xia

    2011-01-01

    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ∼ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  19. Incorporation of nitric oxide donor into 1,3-dioxyxanthones leads to synergistic anticancer activity.

    Science.gov (United States)

    Liu, Jie; Zhang, Cao; Wang, Huailing; Zhang, Lei; Jiang, Zhenlei; Zhang, Jianrun; Liu, Zhijun; Chen, Heru

    2018-05-10

    Fifty 1,3-dioxyxanthone nitrates (4a ∼ i-n, n = 1-6) were designed and synthesized based on molecular similarity strategy. Incorporation of nitrate into 1,3-dioxyxanthones with electron-donating groups at 6-8 position brought about synergistic anticancer effect. Among them, compound 4g-4 was confirmed the most active agent against HepG-2 cells growth with an IC 50 of 0.33 ± 0.06 μM. It dose-dependently increased intramolecular NO levels. This activity was attenuated by either NO scavenger PTIO or mitochondrial aldehyde dehydrogenase (mtADH) inhibitor PCDA. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for different dose of 4g-4. 4g-4 arrested more cells on S phase. Results from Western Blot implied that 4g-4 regulated p53/MDM2 to promote cancer cell apoptosis. All the evidences support that 4g-4 is a promising anti-cancer agent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    Energy Technology Data Exchange (ETDEWEB)

    Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Zheng Lan; Zhao Xia, E-mail: anderson-qian@163.com [West China Second University Hospital, West China Women' s and Children' s Hospital, Sichuan University, Chengdu 610041 (China)

    2011-03-04

    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly({epsilon}-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and {approx} 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  1. Anticancer activity of drug conjugates in head and neck cancer cells.

    Science.gov (United States)

    Majumdar, Debatosh; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Shin, Dong M

    2016-06-01

    Sexually transmitted oral cancer/head and neck cancer is increasing rapidly. Human papilloma virus (HPV) is playing a role in the pathogenesis of a subset of squamous cell carcinoma of head and neck (SCCHN). Paclitaxel is a widely used anticancer drug for breast, ovarian, testicular, cervical, non-small cell lung, head and neck cancer. However, it is water insoluble and orally inactive. We report the synthesis of water soluble nanosize conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide by employing native chemical ligation. We performed a native chemical ligation between the N-hydroxy succinimide (NHS) ester of paclitaxel succinate and cysteine at pH 6.5 to give the cysteine-conjugated paclitaxel derivative. The thiol functionality of cysteine was activated and subsequently conjugated to multiarm thiol-PEG to obtain the paclitaxel branched PEG conjugate. Finally, we conjugated an EGFR-targeting peptide to obtain conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide. These conjugates show anticancer activity against squamous cell carcinoma of head and neck cells (SCCHN, Tu212).

  2. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński

    2013-08-01

    Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

  3. Evaluation of DNA-damaging marine natural product with potential anticancer activity

    International Nuclear Information System (INIS)

    Nisa, M.; Amjad, S.; Chaudhary, M.I.; Sualah, R.; Khan, S.H.

    2002-01-01

    The treatment for the dreadful disease cancer require a continued development of novel and improved chemo preventive and chemotherapeutic agents. An exploitable feature of tumor cell is that it has defect in its ability to repair damage to DNA as compared with normal cell, suggesting that agent with selective toxicity towards DNA repair deficient cell might be potential anticancer agent. In a recently developed mechanism based approach discovery. DNA repair a recombination-deficient mutants of the yeast Saccharomyces cerevisiae were utilized, as yeast and bacteria are the popular genetically engineered microorganisms. We have scanned organic solvent extracts of about thirty five different species of marine flora and fauna under DNA-damaging activity assays. Marine plants showed no activity towards this bioassay, whereas marine animals tested under this bioassay showed good activity. Detail results of our studies will be discussed in this paper. (author)

  4. Antioxidant, anticancer and anticholinesterase activities of flower, fruit and seed extracts of Hypericum amblysepalum HOCHST.

    Science.gov (United States)

    Keskin, Cumali

    2015-01-01

    Cancer is an unnatural type of tissue growth in which the cells exhibit unrestrained division, leading to a progressive increase in the number of dividing cells. It is now the second largest cause of death in the world. The present study concerned antioxidant, anticancer and anticholinesterase activities and protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in methanol extracts of flowers, fruits and seeds of Hypericum amblysepalum. Antioxidant properties including free radical scavenging activity and reducing power, and amounts of total phenolic compounds were evaluated using different tests. Protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in extracts were determined by HPLC. Cytotoxic effects were determined using the MTT test with human cervix cancer (HeLa) and rat kidney epithelium cell (NRK-52E) lines. Acetyl and butyrylcholinesterase inhibitory activities were measured by by Ellman method. Total phenolic content of H. amblysepalum seeds was found to be higher than in fruit and flower extracts. DPPH free radical scavenging activity of the obtained extracts gave satisfactory results versus butylated hydroxyanisole and butylated hydroxytoluene as controls. Reducing power activity was linearly proportional to the studied concentration range: 10-500 μg/ mL LC50 values for H. amblysepalum seeds were 11.7 and 2.86 respectively for HeLa and NRK-52E cell lines. Butyryl-cholinesterase inhibitory activity was 76.9±0.41 for seed extract and higher than with other extracts. The present results suggested that H. amblysepalum could be a potential candidate anti-cancer drug for the treatment of human cervical cancer, and good source of natural antioxidants.

  5. Anticancer peptides from bacteria

    OpenAIRE

    Tomasz M. Karpiński; Anna K. Szkaradkiewicz

    2013-01-01

    Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data ...

  6. Anticancer activity of litchi fruit pericarp extract against human breast cancer in vitro and in vivo

    International Nuclear Information System (INIS)

    Wang Xiujie; Yuan Shulan; Wang Jing; Lin Ping; Liu Guanjian; Lu Yanrong; Zhang Jie; Wang, Wendong; Wei Yuquan

    2006-01-01

    Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic compounds and exhibits powerful antioxidative activity against fat oxidation in vitro. The purpose of this study is to confirm the anticancer activity of LFP extract on human breast cancer in vitro and in vivo, and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation, and gene expression profiling after treatment with LFP extract. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for its anticancer activity and expression of caspase-3 in vivo by oral administration of 0.3% (0.3 mg/ml) of LFP water-soluble crude ethanolic extract (CEE) for 10 weeks. LFP extract demonstrated a dose- and time-dependent inhibitory effect on cell growth (IC 5 = 80 μg/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41(1.22%) up-regulated and 129 (3.84%) down-regulated genes after LFP water-soluble CEE treatment; the predominantly up-regulated genes were involved in various biological functions including cell cycle regulation and cell proliferation, apoptosis, signal transduction and transcriptional regulation, and extracellular matrix/adhesion molecules; and down-regulated genes were mainly associated with adhesion, invasion, and malignancy of cancer cells. A 40.70% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo experiment. The findings in this study suggested that LFP extract might have potential anticancer activity on both ER positive and negative breast cancers, which could be attributed, in part, to its DNA damage effect, proliferating inhibition and apoptosis induction of cancer cells through up-regulation and down-regulation of multiple genes involved in cell cycle regulation and cell

  7. The Anticancer Activity of Sea Buckthorn [Elaeagnus rhamnoides (L. A. Nelson

    Directory of Open Access Journals (Sweden)

    Beata Olas

    2018-03-01

    Full Text Available Various parts of sea buckthorn [Elaeagnus rhamnoides (L. A. Nelson], particularly the berries, known also as seaberries, or Siberian pineapples, are characterized by a unique composition of bioactive compounds: phenolic compounds, vitamins (especially vitamin C, unsaturated fatty acids, and phytosterols such as beta-sitosterol. These berries, together with the juices, jams, and oils made from them, have a range of beneficial antioxidant, anti-inflammatory, and anticancer effects. This short review discusses whether sea buckthorn may represent a “golden mean” for the treatment of cancers: It has anti-proliferation properties and can induce apoptosis and stimulate the immune system, and sea buckthorn oil counteracts many side effects of chemotherapy by restoring kidney and liver function, increasing appetite, and keeping patients in general good health. Although the anticancer activity of sea buckthorn has been confirmed by many in vitro and animal in vivo studies, the treatment and prophylactic doses for humans are unknown. Therefore, greater attention should be paid to the development of well-controlled and high-quality clinical experiments in this area.

  8. The application of click chemistry in the synthesis of agents with anticancer activity

    Directory of Open Access Journals (Sweden)

    Ma N

    2015-03-01

    Full Text Available Nan Ma,1–3 Ying Wang,3 Bing-Xin Zhao,3 Wen-Cai Ye,1,3 Sheng Jiang2 1Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 2Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 3Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China Abstract: The copper(I-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility. This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly. The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents. Keywords: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, antimicrotubule agents

  9. Maltese Mushroom (Cynomorium coccineum L. as Source of Oil with Potential Anticancer Activity

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    Antonella Rosa

    2015-01-01

    Full Text Available The present study aimed to examine the potential anticancer properties of fixed oil obtained from Maltese mushroom (Cynomorium coccineum L., an edible, non-photosynthetic plant, used in traditional medicine of Mediterranean countries to treat various ailments and as an emergency food during the famine. We investigated the effect of the oil, obtained from dried stems by supercritical fractioned extraction with CO2, on B16F10 melanoma and colon cancer Caco-2 cell viability and lipid profile. The oil, rich in essential fatty acids (18:3n-3 and 18:2n-6, showed a significant growth inhibitory effect on melanoma and colon cancer cells. The incubation (24 h with non-toxic oil concentrations (25 and 50 μg/mL induced in both cancer cell lines a significant accumulation of the fatty acids 18:3n-3 and 18:2n-6 and an increase of the cellular levels of eicosapentaenoic acid (20:5n-3 with anticancer activity. Moreover, the oil exhibited the ability to potentiate the growth inhibitory effect of the antitumor drug 5-fluorouracil in Caco-2 cells and to influence the melanin content in B16F10 cells. The results qualify C. coccineum as a resource of oil, with potential benefits in cancer prevention, for nutraceutical and pharmaceutical applications.

  10. Anti-cancer activity of tectona hamiltoniana-an endemic plant of Myanmar

    International Nuclear Information System (INIS)

    Mya, K.M.; Shyaula, S.L.

    2012-01-01

    Summary: The ethanolic extracts of barks and leaves of Tectona hamiltoniana (Verbenaceae) were tested for anti-cancer activity against MCF-7 (Human breast cancer) and NCI-H460 (Lung cancer) cell lines employing sulpho rhodamine B (SRB) bioassay. These extracts demonstrated cytotoxicity with GI/sub 50/ values ranging between 24-33 macro g/mL against both cell lines. Upon further fractionation, dichloromethane fraction appeared to be most active against the MCF-7 cell line (GI/sub 50/ value of 3.4+-0.9 macro g/mL) leading to the isolation of lupane type triterpenoids, betulinic acid (1), betulin aldehyde ( 2 ) and betulin (3). Compound 2 and 3, both showed significant cytotoxic effect against both cancerous cell lines (GI/sub 50/ value range 6-11 macro M). (author)

  11. Studies on synthesis and anticancer activity of selected N-(2-fluoroethyl)-N-nitrosoureas.

    Science.gov (United States)

    Johnston, T P; Kussner, C L; Carter, R L; Frye, J L; Lomax, N R; Plowman, J; Narayanan, V L

    1984-11-01

    An activated carbamate, 2-nitrophenyl (2-fluoroethyl)nitrosocarbamate (3), was used to advantage in the synthesis of the water-soluble (2-fluoroethyl)nitrosoureas 6a--d from 2-aminoethanol, (1 alpha, 2 beta, 3 alpha)-2-amino-1,3-cyclohexanediol, cis-2-hydroxycyclohexanol, and 2-amino-2-deoxy-D-glucose. In a variation of this method, 2,4,5-trichlorophenyl (2-fluoroethyl)carbamate (4) was used to prepare the urea from which the essentially water-insoluble N-(2,6-dioxo-3-piperidinyl)-N-(2-fluoroethyl)-N-nitrosourea (6e) was derived. The anticancer activity of these nitrosoureas was determined against the murine tumors B16 melanoma and Lewis lung carcinoma and found to be significant and comparable to their chloroethyl counterparts. On the basis of results from both systems, the dihydroxycyclohexyl derivative 6b may be the most effective.

  12. Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

    KAUST Repository

    Hasan, Mohammed Nihal

    2018-02-09

    Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

  13. Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

    KAUST Repository

    Hasan, Mohammed Nihal; Choudhry, Hani; Razvi, Syed Shoeb; Moselhy, Said Salama; Kumosani, Taha Abduallah; Zamzami, Mazin A.; Omran, Ziad; Halwani, Majed A.; Al-Babili, Salim; Abualnaja, Khalid Omer; Al-Malki, Abdulrahman Labeed; Alhosin, Mahmoud; Asami, Tadao

    2018-01-01

    Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

  14. Anticancer activity and apoptosis inducing effect of methanolic extract of Cordia dichotoma against human cancer cell line

    Directory of Open Access Journals (Sweden)

    Md. Azizur Rahman

    2015-03-01

    Full Text Available MTT assay and DAPI staining test were performed to evaluate anticancer potential and to assess apoptosis inducing effect of methanolic extract of Cordia dichotoma leaves (MECD against human cervical cancer cell line (HeLa. Changes in MMP and intracellular ROS level were also assessed by JC-1 and DCFH-DA staining. Total phenolic contents were determined by colorimetric principle. Levels of statistical significance were determined by one-way analysis of variance followed by Dunnett’s posttest. Results showed that MECD with obtained IC50 of 202 µg/mL inhibited in vitro proliferation of human cervical cancer cells and induced apoptosis indicating its promising anticancer activity as compared to the standard tamoxifen with obtained IC50 of 48 µg/mL. Total phenolic contents was found to be 176.5 mg GAE/g dried extract. It was concluded that MECD possess promising anticancer activity and induce apoptosis.

  15. In Vitro and In Vivo Anticancer Activity of Root Extracts of Sansevieria liberica Gerome and Labroy (Agavaceae

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    Abidemi J. Akindele

    2015-01-01

    Full Text Available Introduction. Sansevieria liberica Gerome and Labroy (Agavaceae is a perennial plant widely distributed in tropical Africa. Preparations of the plant are commonly used across Nigeria for the treatment of inflammatory conditions. Based on the fact that herbal medicine is a strong component of integrative medicine, this study was conducted to evaluate the anticancer activity of root extracts of Sansevieria liberica. Methods. Sulforhodamine B (SRB in vitro cytotoxicity assay, Sarcoma-180 (S-180 ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used in this study. Results. SL-A002 (IC50 23 µg/mL with HeLa, SL-A003 (IC50 22 µg/mL with HCT-116, and SL-A004 (IC50 23 and 18 µg/mL with A549 and THP-1, resp. demonstrated significant activity in the SRB cytotoxicity assay. Potency was highest with the following pairs of extract : cancer cell line: SL-A002 : HeLa (IC50 23 µg/mL, SL-A003 : HCT-116 (IC50 22 µg/mL, and SL-A004 : THP-1 (IC50 18 µg/mL. SL-A002 demonstrated significant dose-dependent antitumor activity in the Sarcoma-180 (S-180 ascites model with peak effect produced at the dose of 120 mg/kg (i.p. with inhibition of 89.36% compared to 97.96% for 5-FU (20 mg/kg i.p.. The inhibition of tumor growth by SL-A002 in the S-180 solid tumor model was 47.40% compared to a value of 50.18% for 5-FU. SL-A002 was also significantly active in the L1210 lymphoid leukemia model with 158.33% increase in mean survival time, the same value for 5-FU. Conclusions. The hydroethanolic extract of Sansevieria liberica, SL-A002, possesses significant anticancer activity to warrant further extensive study to identify, isolate, and characterize the specific bioactive molecules responsible for the observed antitumor activity and the precise mechanism(s of action.

  16. Biosynthesis of Silver Nanoparticles Using Oscillatoria Extract and Evaluation the Anticancer and Antibacterial Activities

    Directory of Open Access Journals (Sweden)

    T Ghasemipour

    2017-07-01

    Full Text Available Abstract Background and aim: The emergence of nanotechnology is one of the most promising areas for medical research. Today, biological methods of synthesizing nanoparticles have been considered in the fight against many diseases. The purpose of this study was to evaluate the anti-cancer and anti-bacterial activity of silver nanoparticles, biosynthesized with cyanobacteria acetate extract. Methods: In the present experimental study, the silver nanoparticles biosynthesis was performed using silver ions regeneration with cyanobacteria acetate extracts. Techniques such as X-ray diffraction, scanning electron microscopy and transient evaluation of silver nanoparticles were evaluated. In order to investigate the antibacterial activity of synthesized nanosilver, serial dilution method was used for broth microdilution test to determine minimum inhibitory concentration (MIC. The effects of silver nanoparticle toxicity on T47D breast cancer cell line were evaluated using MTT colorimetric method. Also, the proximal anxine 0.5 propidoid yodide kit and flow cytometry system were evaluated to evaluate the percentage of apoptosis and necrosis in cancer cells treated with silver nanoparticles. Results: Characterization of biosynthetic silver nanoparticles indicated that these nanoparticles had a mean size of 30 nm with dominant spherical morphology. The evaluation of the antibacterial properties of biosynthetic nanoparticles showed that the minimum inhibitory concentration for Escherichia coli, Acinetobacter Bumanni and Staphylococcus aureus was 25, 50 and 12.5 μg / ml, respectively. The results of cell proliferation of nanoparticles showed that its effect depends on the concentration and time of treatment of silver nanoparticles on cancerous cells. In addition, flow cytometric results showed an apoptotic cell death rate of 35% in the T47D cell line. Conclusion: Biosynthesis nanoparticles have anticancer and antibacterial activity and can be studied further

  17. Chiral halogenated Schiff base compounds: green synthesis, anticancer activity and DNA-binding study

    Science.gov (United States)

    Ariyaeifar, Mahnaz; Amiri Rudbari, Hadi; Sahihi, Mehdi; Kazemi, Zahra; Kajani, Abolghasem Abbasi; Zali-Boeini, Hassan; Kordestani, Nazanin; Bruno, Giuseppe; Gharaghani, Sajjad

    2018-06-01

    Eight enantiomerically pure halogenated Schiff base compounds were synthesized by reaction of halogenated salicylaldehydes with 3-Amino-1,2-propanediol (R or S) in water as green solvent at ambient temperature. All compounds were characterized by elemental analyses, NMR (1H and 13C), circular dichroism (CD) and FT-IR spectroscopy. FS-DNA binding studies of these compounds carried out by fluorescence quenching and UV-vis spectroscopy. The obtained results revealed that the ligands bind to DNA as: (Rsbnd ClBr) > (Rsbnd Cl2) > (Rsbnd Br2) > (Rsbnd I2) and (Ssbnd ClBr) > (Ssbnd Cl2) > (Ssbnd Br2) > (Ssbnd I2), indicating the effect of halogen on binding constant. In addition, DNA-binding constant of the Ssbnd and R-enantiomers are different from each other. The ligands can form halogen bonds with DNA that were confirmed by molecular docking. This method was also measured the bond distances and bond angles. The study of obtained data can have concluded that binding affinity of the ligands to DNA depends on strength of halogen bonds. The potential anticancer activity of ligands were also evaluated on MCF-7 and HeLa cancer cell lines by using MTT assay. The results showed that the anticancer activity and FS-DNA interaction is significantly dependent on the stereoisomers of Schiff base compounds as R-enantiomers displayed significantly higher activity than S-enantiomers. The molecular docking was also used to illustrate the specific DNA-binding of synthesized compounds and groove binding mode of DNA interaction was proposed for them. In addition, molecular docking results indicated that there are three types of bonds (Hsbnd and X-bond and hX-bond) between synthesized compounds and base pairs of DNA.

  18. Dendritic cells for active anti-cancer immunotherapy: targeting activation pathways through genetic modification.

    Science.gov (United States)

    Breckpot, Karine; Escors, David

    2009-12-01

    Tumour immunotherapy has become a treatment modality for cancer, harnessing the immune system to recognize and eradicate tumour cells specifically. It is based on the expression of tumour associated antigens (TAA) by the tumour cells and aims at the induction of TAA-specific effector T cell responses, whilst overruling various mechanisms that can hamper the anti-tumour immune response, e.g. regulatory T cells (Treg). (Re-) activation of effector T cells requires the completion of a carefully orchestrated series of specific steps. Particularly important is the provision of TAA presentation and strong stimulatory signals, delivered by co-stimulatory surface molecules and cytokines. These can only be delivered by professional antigen-presenting cells, in particular dendritic cells (DC). Therefore, DC need to be loaded with TAA and appropriately activated. It is not surprising that an extensive part of DC research has focused on the delivery of both TAA and activation signals to DC, developing a one step approach to obtain potent stimulatory DC. The simultaneous delivery of TAA and activation signals is therefore the topic of this review, emphasizing the role of DC in mediating T cell activation and how we can manipulate DC for the pill-pose of enhancing tumour immunotherapy. As we gain a better understanding of the molecular and cellular mechanisms that mediate induction of TAA-specific T cells, rational approaches for the activation of T cell responses can be developed for the treatment of cancer.

  19. A potential photocatalytic, antimicrobial and anticancer activity of chitosan-copper nanocomposite.

    Science.gov (United States)

    Arjunan, Nithya; Singaravelu, Chandra Mohan; Kulanthaivel, Jeganathan; Kandasamy, Jothivenkatachalam

    2017-11-01

    In this study, chitosan-copper (CS-Cu) nanocomposite was synthesized without the aid of any external chemical reducing agents. The optical, structural, spectral, thermal and morphological analyses were carried out by several techniques. The prepared nanocomposite acts as a photocatalyst for the removal of Rhodamine B (RhB) and Conge red (CR) dyes under visible light irradiation. The pseudo first order kinetics was derived according to Langmuir-Hinshelwood (L-H) model. The nanocomposite also proved to be an excellent antimicrobial agent against Gram-positive and Gram-negative bacteria; and also show activity against fungus. The advanced material was used for the major research areas which include photocatalytic materials for waste water treatment; biological applications in the development of drug resistant antimicrobials and anticancer agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Francesca Carlini

    Full Text Available BACKGROUND: Transposable Elements (TEs comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1 and Human Endogenous Retroviruses (HERVs that code for their own endogenous reverse transcriptase (RT. Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC, a nucleoside reverse transcription inhibitor (NRTI, on PC3 and LNCaP prostate cancer cell lines. PRINCIPAL FINDINGS: ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. CONCLUSIONS: Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications.

  1. Equivalent anticancer activities of dietary vitamin D and calcitriol in an animal model of breast cancer: importance of mammary CYP27B1 for treatment and prevention.

    Science.gov (United States)

    Krishnan, Aruna V; Swami, Srilatha; Feldman, David

    2013-07-01

    Calcitriol [1,25(OH)2D3], the hormonally active form of vitamin D exerts anti-proliferative, pro-apoptotic, anti-inflammatory effects and other anticancer actions in breast cancer (BCa) cell cultures and animal models of BCa. Our research is focused on investigating the potential beneficial effects of dietary vitamin D3 compared to calcitriol and the underlying mechanisms in BCa treatment and chemoprevention. We recently found that dietary vitamin D3 exhibits significant tumor inhibitory effects in xenograft models of BCa that are equivalent to those elicited by the administration of the active hormone calcitriol. At the easily achievable dose tested in our studies, dietary vitamin D3 exhibited substantial tumor inhibitory activity and, unlike calcitriol, did not cause hypercalcemia demonstrating its relative safety. We found elevations in circulating calcitriol as well as increased CYP27B1 expression in the tumor and the intestine in tumor-bearing mice ingesting a vitamin D3-supplemented diet. We hypothesize that the elevation in circulating 25(OH)D induced by dietary vitamin D3 supplements stimulates local synthesis of calcitriol in the mammary tumor microenvironment and the ensuing paracrine/autocrine actions play a major role in the anticancer activity of dietary vitamin D3. Our findings suggest that the endocrine activity of calcitriol derived from tumor and other extra-renal sources such as the intestine, probably also plays a role in mediating the anticancer effects of dietary vitamin D3. Thus it appears that multiple sites of 1α-hydroxylation contribute to the anticancer effects of dietary vitamin D3. Our data strongly suggest that dietary vitamin D will be useful in the chemoprevention and treatment of BCa since it is a safe, economical and easily available nutritional agent that is equivalent to calcitriol in exerting anticancer effects, at least in mouse models. Furthermore, adequate vitamin D nutrition and avoidance of vitamin D deficiency appear to be

  2. Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

    Directory of Open Access Journals (Sweden)

    Maria P. Crespo-Ortiz

    2012-01-01

    Full Text Available Improvement of quality of life and survival of cancer patients will be greatly enhanced by the development of highly effective drugs to selectively kill malignant cells. Artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity. In primary cancer cultures and cell lines, their antitumor actions were by inhibiting cancer proliferation, metastasis, and angiogenesis. In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression. However, the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects. The primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated. The aim of this paper is to provide an overview of the recent advances and new development of this class of drugs as potential anticancer agents.

  3. Facile synthesis of indole-pyrimidine hybrids and evaluation of their anticancer and antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Nikhila Gokhale

    2017-11-01

    Full Text Available The paper describes the facile synthesis of new N-cyclopropyl-1-methyl-1H-indole-2-carboxamide derivatives bearing substituted 2-amino pyrimidine moiety at position-3 of the indole ring. All the intermediate and title compounds were characterized adeptly by 1H NMR, 13C NMR, ESI–MS and elemental analyses. These compounds were evaluated for their in vitro anticancer activity against HeLa, HepG2 and MCF-7 cells. Three among 22 molecules, showed more than 70% growth inhibition against all three tested cancer cells. The nature of the substituent group on the pyrimidine ring (R2 affected significantly the anti-proliferative activity of the molecules. The anti-microbial evaluation of the title molecules revealed the significance of fluoro/chloro groups (R2 in enhancing their inhibition activity. Eight molecules which contain fluoro/chloro groups showed potent anti-microbial activity. In addition, the active molecules displayed negligible toxicity to benign Vero cells.

  4. Antioxidant, antifungal and anticancer activities of se-enriched Pleurotus spp. mycelium extracts

    Directory of Open Access Journals (Sweden)

    Milovanović Ivan

    2014-01-01

    Full Text Available The goal of this study was the evaluation of antifungal, antioxidant and anticancer potentials of Pleurotus eryngii, P. ostreatus and P. pulmonarius mycelial extracts, and the influence of mycelium enrichment with selenium on these activities. Both Se-amended and non-amended extracts showed the same or similar minimal inhibitory concentration for 14 studied micromycetes, while a fungicidal effect was not noted, contrary to ketoconazole, which had inhibitory and fungicidal effects at very low concentrations. Se-non-amended extracts exhibited antioxidant activity, especially at higher concentrations. Selenium enrichment influenced activity, its effects decreasing in P. eryngii and P. pulmonarius, while in P. ostreatus no effect was noted. The DPPH• radical scavenging capacity of the extracts was in direct correlation with their phenol and flavonoid contents. Cytotoxic activity against both HeLa and LS174 cell lines was very low compared with cis-DDP. These features suggest that mycelium should be an object of intensive studies. [Projekat Ministarstva nauke Republike Srbije, br. 173032

  5. In Vitro Antioxidant, Antihemolytic, and Anticancer Activity of the Carotenoids from Halophilic Archaea.

    Science.gov (United States)

    Hou, Jing; Cui, Heng-Lin

    2018-03-01

    Halophilic archaea represent a promising natural source of carotenoids. However, little information is available about the biological effects of carotenoids from halophilic archaea. In this study, the carotenoids produced by seven halophilic archaeal strains Halogeometricum rufum, Halogeometricum limi, Haladaptatus litoreus, Haloplanus vescus, Halopelagius inordinatus, Halogranum rubrum, and Haloferax volcanii were identified by ultraviolet/visible spectroscopy, thin-layer chromatography, and high-performance liquid chromatography-tandem mass spectrometry. The C 50 carotenoids bacterioruberin and its derivatives monoanhydrobacterioruberin and bisanhydrobacterioruberin were found to be the predominant carotenoids. The antioxidant capacities of the carotenoids from these strains were significantly higher than β-carotene as determined by 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. The antihemolytic activities of these carotenoid extracts against H 2 O 2 -induced hemolysis in mouse erythrocytes were 3.9-6.3 times higher than β-carotene. A dose-dependent in vitro antiproliferative activity against HepG2 cells was observed for the extract from Hgm. limi, while that from Hpn. vescus exhibited a relatively high activity in a dose-independent manner. These results suggested that halophilic archaea could be considered as an alternative source of natural carotenoids with high antioxidant, antihemolytic, and anticancer activity.

  6. Recent Advances in the Synthesis and Anticancer Activity of Some Molecules Other Than Nitrogen Containing Heterocyclic Moeities.

    Science.gov (United States)

    Akhtar, Md Jawaid; Yar, M Shahar; Khan, Ahsan Ahmed; Ali, Zulphikar; Haider, Md Rafi

    2017-01-01

    The present review article presented a detailed account of the design strategies and the structure activity relationship of different derivatives apart from the nitrogen containing ring. These scaffolds play an important part in the drug discovery which showed anticancer activity against different human cancer cell lines through apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others. Naphthalenes amides/amidines, furan, podophyllotoxin, platinum compounds, steroids, and urea, which forms the core part or along with other N-heterocyclic rings are enclosed. Some of these compounds e.g. podophyllotoxin and platinum based drugs displayed anticancer activity at nanomolar range. Various substitutions from the earlier and latest information are prerequisite in the drug synthesis process. The review focused on the recent development of these derivatives, design and anticancer properties, thus providing with the most profound knowledge for the development of targeted based anticancer drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Anticancer Activity of Ramalin, a Secondary Metabolite from the Antarctic Lichen Ramalina terebrata, against Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sung-Suk Suh

    2017-08-01

    Full Text Available Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer cells, making them promising candidates for new anticancer therapeutic drugs. The main objective of this study was to evaluate the anticancer capacities of ramalin, a secondary metabolite from the Antarctic lichen Ramalina terebrata, in the human colorectal cancer cell line HCT116. In this study, ramalin displayed concentration-dependent anticancer activity against HCT116 cells, significantly suppressing proliferation and inducing apoptosis. Furthermore, ramalin induced cell cycle arrest in the gap 2/mitosis (G2/M phase through the modulation of hallmark genes involved in the G2/M phase transition, such as tumour protein p53 (TP53, cyclin-dependent kinase inhibitor 1A (CDKN1A, cyclin-dependent kinase 1 (CDK1 and cyclin B1 (CCNB1. At both the transcriptional and translational level, ramalin caused a gradual increase in the expression of TP53 and its downstream gene CDKN1A, while decreasing the expression of CDK1 and CCNB1 in a concentration-dependent manner. In addition, ramalin significantly inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that ramalin may be a therapeutic candidate for the targeted therapy of colorectal cancer.

  8. Ultrasonic extraction, antioxidant and anticancer activities of novel polysaccharides from Chuanxiong rhizome.

    Science.gov (United States)

    Hu, Jie; Jia, Xuejing; Fang, Xiaobin; Li, Peng; He, Chengwei; Chen, Meiwan

    2016-04-01

    Ultrasonic-assisted extraction technology was employed to prepare Ligusticum chuanxiong Hort polysaccharide. Single factor test and orthogonal experimental design were used to optimize the extraction conditions. The results showed that the optimal extraction conditions consisted of ultrasonic temperature of 80°C, ultrasonic time of 40 min and water to raw material ratio of 30 mL/g. Three novel polysaccharides fractions, LCX0, LCX1 and LCX2, were isolated and purified from the crude polysaccharides using DEAE-52 cellulose and Sephadex G-100 column chromatography. The molecular weight and monosaccharide composition of three LCX polysaccharides fractions were analyzed with gel permeation chromatography (GPC) and HPLC analysis, respectively. Furthermore, the antioxidant and in vitro anticancer activities of the polysaccharides were investigated. Compared with LCX0, LCX2 and LCX1 showed relative higher antioxidant activity and inhibitory activity to the growth of HepG2, SMMC7721, A549 and HCT-116 cells. It is suggested that the novel polysaccharides from rhizome of L. chuanxiong could be promising bioactive macromolecules for biomedical use. Copyright © 2016. Published by Elsevier B.V.

  9. Starch-templated bio-synthesis of gold nanoflowers for in vitro antimicrobial and anticancer activities

    Science.gov (United States)

    Borah, D.; Hazarika, M.; Tailor, P.; Silva, A. R.; Chetia, B.; Singaravelu, G.; Das, P.

    2018-05-01

    We describe an in situ method of synthesizing highly branched gold nanoflower (AuNFs) using aqueous seed extract of Syzygium cumini (L.) Skeels as reductant in the presence of 0.3% starch. Surprisingly, when the same reaction was carried out in the absence of starch or with starch at a lower concentration (0.15%), instead of flower-like morphology quasi-spherical or polyhedral nanoparticles (AuNPs) are obtained. The nanomaterials were extensively characterized by HRTEM, FESEM, UV-Vis, FTIR, XRD, XPS and TGA analysis. The biological activities of the materials were investigated for antimicrobial activities against four bacterial strains that include one Gram positive (Staphylococcus aureus MTCC 121), two Gram negative (Escherichia coli MTCC 40 and Pseudomonas aeruginosa MTCC 4673) and one fungi (Candida albicans MTCC 227). The nanoparticles functioned as effective antimicrobial and anti-biofilm agents against all the strains under study. Controlled study revealed that, the AuNFs showed improved efficacy over conventional polyhedral AuNPs against all the microbes under study which might be attributed to the larger surface-to-volume ratio of the nanoflowers. The AuNFs also showed effective in vitro anticancer activity against a human liver cancer cell line (HepG2) with no significant cytotoxicity. Our data suggest that the AuNFs can significantly reduce the cancer cell growth with IC50 value of 20 µg mL-1.

  10. Synthesis of isatin thiosemicarbazones derivatives: in vitro anti-cancer, DNA binding and cleavage activities.

    Science.gov (United States)

    Ali, Amna Qasem; Teoh, Siang Guan; Salhin, Abdussalam; Eltayeb, Naser Eltaher; Khadeer Ahamed, Mohamed B; Abdul Majid, A M S

    2014-05-05

    New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k(b)=5.03-33.00×10(5) M(-1)) for L1-L3 and L5 and (6.14-9.47×10(4) M(-1)) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Synthesis, characterization, and anticancer activity of new quinazoline derivatives against MCF-7 cells.

    Science.gov (United States)

    Faraj, Fadhil Lafta; Zahedifard, Maryam; Paydar, Mohammadjavad; Looi, Chung Yeng; Abdul Majid, Nazia; Ali, Hapipah Mohd; Ahmad, Noraini; Gwaram, Nura Suleiman; Abdulla, Mahmood Ameen

    2014-01-01

    Two new synthesized and characterized quinazoline Schiff bases 1 and 2 were investigated for anticancer activity against MCF-7 human breast cancer cell line. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an IC50 value of 6.246×10(-6) mol/L and 5.910×10(-6) mol/L, respectively, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with 1 and 2 subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS formation. We also found activation of caspases-3/7, -8, and -9 in compounds 1 and 2. Moreover, inhibition of NF-κB translocation in MCF-7 cells treated by compound 1 significantly exhibited the association of extrinsic apoptosis pathway. Acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed significant activity towards MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway and are potential candidate for further in vivo and clinical breast cancer studies.

  12. Biological activity of soils strongly polluted with sulfur

    Energy Technology Data Exchange (ETDEWEB)

    Krol, M; Maliszewska, W; Siuta, J

    1972-01-01

    Studies were carried out on soils strongly polluted with sulfur and acidified (to pH 1.4). The soils were subjected to an intensive liming. In field and pot experiments, the authors determined: the total quantity of bacteria, actinomycetes, fungi, azotobacter, nitrifiers, proteolytic activity of microorganisms, activity of ammonifiers and the number of sulfur-oxidizing and sulfate-reducing bacteria. It was found that intensive liming of sulfur-affected soils restored their biological activity. 8 references, 5 figures, 1 table.

  13. Alcoholic Extract of Eclipta alba Shows In Vitro Antioxidant and Anticancer Activity without Exhibiting Toxicological Effects

    Directory of Open Access Journals (Sweden)

    Navneet Kumar Yadav

    2017-01-01

    Full Text Available As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA-MB-231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer.

  14. Synthesis, structure characterization, and anticancer activity of a novel oxygen-bridged tricyclic Biginelli adduct

    Science.gov (United States)

    Ibrahim, Mohamed M.; El-Sheshtawy, Hamdy S.; El-Kemary, Maged; Al-Juaid, Salih; Youssef, Mohamed; El-Azab, Islam H.

    2017-06-01

    Herein, we report the one-pot cyclization of Biginelli Adduct, ethyl 4-(2-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (I) to the oxygen-bridged adduct, ethyl 2-methyl-4-thioxo-3,4,5,6-tetrahydro-2H-2,6-methanobenzo[g] [1,3,5]oxadiazocine-11-carboxylate (II) in a high yield and purity under mild reaction condition using zinc(II) perchlorate hexahydrate as a highly efficient catalyst. The cyclic product (II) was characterized both in the solid state and in solution using FT-IR, 1H NMR, and UV-visible spectroscopy. Theoretical calculations using density functional theory with B3LYP/6-311++G(d,p) level were used to further investigate the structure properties. DFT calculations (gas phase) revealed the stability of cyclic compound II (3.45 kcal/mol) than compound I. In addition, the anticancer activity of II was investigated using MCF-7 human breast cell line. The results revealed a moderate activity with 223.55 μg/ml IC50 value.

  15. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database.

    Science.gov (United States)

    Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P S; Agarwal, Subhash M

    2013-01-01

    Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC(50)/ED(50)/EC(50)/GI(50)), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients' Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI(50) data.

  16. Anticancer activity of Cynodon dactylon L. root extract against diethyl nitrosamine induced hepatic carcinoma.

    Science.gov (United States)

    Kowsalya, R; Kaliaperumal, Jagatheesh; Vaishnavi, M; Namasivayam, Elangovan

    2015-01-01

    Hepatocellular carcinoma is one of the most common cancers and a lethal disease. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. The methanolic extract of roots of Cynodon dactylon was screened for its hepato-protective activity in diethyl nitrosamine (DEN) induced liver cancer in Swiss albino mice. The plant extract at a dose of 50 mg/kg was administered orally once a week, up to 30 days after DEN administration. The animals were sacrificed; blood sample and liver tissue were collected and used for enzyme assay such as, asparatate amino transferase (AST), alanine aminotransferase (ALT), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The liver marker enzymes AST and ALT produced significant results in the protective action. The antioxidant enzyme assay results concerning the improved activity of GPx, GST and CAT. These results concluded that enhanced levels of antioxidant enzyme and reduced amount of serum amino transaminase, which are suggested to be the major mechanisms of C. dactylon root extract in protecting the mice from hepatocarcinoma induced by DEN. These biochemical observations were supplemented by histopathological examination of liver sections. The methanolic extract of C. dactylon possesses significant anticancer properties.

  17. Anticancer activity of Kalanchoe tubiflora extract against human lung cancer cells in vitro and in vivo.

    Science.gov (United States)

    Hsieh, Yi-Jen; Huang, Hsuan-Shun; Leu, Yann-Lii; Peng, Kou-Cheng; Chang, Chih-Jui; Chang, Meng-Ya

    2016-11-01

    Uncontrolled cell proliferation is a common feature of human cancer. Some of herbal extract or plant-derived medicine had been shown as an important source of effective anticancer agents. We previously reported that an n-BuOH-soluble fraction of Kalanchoe tubiflora has antiproliferative activity by inducing mitotic catastrophe. In this study, we showed that the H 2 O-soluble fraction of Kalanchoe tubiflora (KT-W) caused cell cycle arrest, and senescence-inducing activities in A549 cells. We used 2 dimensional PAGE to analyze the protein expression levels after KT-W treatment, and identified that the energy metabolism-related proteins and senescence-related proteins were disturbed. In vivo experiments showed that the tumor growths in A549-xenografted nude mice were effectively inhibited by KT-W. Our findings implied that KT-W is a putative antitumor agent by inducing cell cycle arrest and senescence. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1663-1673, 2016. © 2015 Wiley Periodicals, Inc.

  18. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database

    Science.gov (United States)

    Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P. S.; Agarwal, Subhash M.

    2013-01-01

    Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC50/ED50/EC50/GI50), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients’ Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI50 data. PMID:23203877

  19. Anti-Cancer Activity of Lobaric Acid and Lobarstin Extracted from the Antarctic Lichen Stereocaulon alpnum

    Directory of Open Access Journals (Sweden)

    Ju-Mi Hong

    2018-03-01

    Full Text Available Lobaric acid and lobarstin, secondary metabolites derived from the antarctic lichen Stereocaulon alpnum, exert various biological activities, including antitumor, anti-proliferation, anti-inflammation, and antioxidant activities. However, the underlying mechanisms of these effects have not yet been elucidated in human cervix adenocarcinoma and human colon carcinoma. In the present study, we evaluated the anticancer effects of lobaric acid and lobarstin on human cervix adenocarcinoma HeLa cells and colon carcinoma HCT116 cells. We show that the proliferation of Hela and HCT116 cells treated with lobaric acid and lobarstin significantly decreased in a dose- and time-dependent manner. Using flow cytometry analysis, we observed that the treatment with these compounds resulted in significant apoptosis in both cell lines, following cell cycle perturbation and arrest in G2/M phase. Furthermore, using immunoblot analysis, we investigated the expression of cell cycle and apoptosis-related marker genes and found a significant downregulation of the apoptosis regulator B-cell lymphoma 2 (Bcl-2 and upregulation of the cleaved form of the poly (ADP-ribose polymerase (PARP, a DNA repair and apoptosis regulator. These results suggest that lobaric acid and lobarstin could significantly inhibit cell proliferation through cell cycle arrest and induction of apoptosis via the mitochondrial apoptotic pathway in cervix adenocarcinoma and colon carcinoma cells. Taken together, our data suggests that lobaric acid and lobarstin might be novel agents for clinical treatment of cervix adenocarcinoma and colon carcinoma.

  20. Anticancer activity of Cynodon dactylon L. root extract against diethyl nitrosamine induced hepatic carcinoma

    Directory of Open Access Journals (Sweden)

    R Kowsalya

    2015-01-01

    Full Text Available Background: Hepatocellular carcinoma is one of the most common cancers and a lethal disease. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. Materials and Methods: The methanolic extract of roots of Cynodon dactylon was screened for its hepato-protective activity in diethyl nitrosamine (DEN induced liver cancer in Swiss albino mice. The plant extract at a dose of 50 mg/kg was administered orally once a week, up to 30 days after DEN administration. The animals were sacrificed; blood sample and liver tissue were collected and used for enzyme assay such as, asparatate amino transferase (AST, alanine aminotransferase (ALT, catalase (CAT, glutathione peroxidase (GPx and glutathione-S-transferase (GST. The liver marker enzymes AST and ALT produced signifi cant results in the protective action. Results: The antioxidant enzyme assay results concerning the improved activity of GPx, GST and CAT. These results concluded that enhanced levels of antioxidant enzyme and reduced amount of serum amino transaminase, which are suggested to be the major mechanisms of C. dactylon root extract in protecting the mice from hepatocarcinoma induced by DEN. These biochemical observations were supplemented by histopathological examination of liver sections. Conclusion: The methanolic extract of C. dactylon possesses signifi cant anticancer properties

  1. Prolonged exposure of colon cancer cells to 5-fluorouracil nanoparticles improves its anticancer activity

    Directory of Open Access Journals (Sweden)

    Essam Tawfik

    2017-02-01

    Full Text Available In this study, we aimed to improve the anticancer effect of 5-FU on human colon cancer cell lines by incorporating in poly(d,l lactic-co-glycolic acid (PLGA nanoparticles (NPs. The 5-FU-PLGA NPs were prepared by nanoprecipitation technique. Prepared NPs were moderately dispersed with an average diameter of 133 ± 25.19 nm. Scanning Electron Microscope (SEM images revealed spherical structures with subtle surface irregularity. Free 5-FU dose–response curves were constructed (12.5–2000 μM using MTT assay on HCT 116 and HT-29 cell lines for 1, 3, and 5 days. The calculated IC50 on HCT 116 were 185 μM after 1 day, 11.3 μM after 3 days, and 1.48 μM after 5 days. On HT-29, IC50 was only reached after 5 days of 5-FU treatment (11.25 μM. The HCT 116 viability following treatment with 100 μM 5-FU in free or NPs forms for 3 days was 38.8% and 18.6%, respectively. Similarly, when 250 μM was applied, HCT 116 viability was 17.03% and 14.6% after treatment with free and NPs forms of 5-FU, respectively. Moreover, HT-29 cell viability after 250 μM 5-FU treatment in free or NPs forms was 55.45% and 34.01%, respectively. We also noticed that HCT 116 cells were more sensitive to 5-FU-PLGA NPs as compared to HT-29 cells. Overall, our data indicate that 5-FU activity is time dependent and the prolonged effects created by PLGA NPs may contribute, at least in part, to the noticed enhancement of the anticancer activity of 5-FU drug.

  2. Anticancer Activity of Toxins from Bee and Snake Venom—An Overview on Ovarian Cancer

    OpenAIRE

    Marius Alexandru Moga; Oana Gabriela Dimienescu; Cristian Andrei Arvătescu; Petru Ifteni; Liana Pleş

    2018-01-01

    Cancer represents the disease of the millennium, a major problem in public health. The proliferation of tumor cells, angiogenesis, and the relationship between the cancer cells and the components of the extracellular matrix are important in the events of carcinogenesis, and these pathways are being used as targets for new anticancer treatments. Various venoms and their toxins have shown possible anticancer effects on human cancer cell lines, providing new perspectives in drug development. In ...

  3. Recent developments in the antiprotozoal and anticancer activities of the 2-alkynoic fatty acids

    Science.gov (United States)

    Carballeira, Néstor M.

    2013-01-01

    The 2-alkynoic fatty acids are an interesting group of synthetic compounds that display antimycobacterial, antifungal, anticancer, and pesticidal activities but their antiprotozoal activity has received little attention until recently. In this review we have summarized our present knowledge of the biomedical potential of the 2-hexadecynoic acid (2-HDA) and 2-octadecynoic acid (2-ODA) together with several mechanistic pieces of work attesting to the fact that these compounds, and their metabolites, are good fatty acid biosynthesis inhibitors. The antiprotozoal activity of 2-HDA and 2-ODA against Leishmania donovani and Plasmodium falciparum, parasites responsible for visceral leishmaniasis and malaria, respectively, is also reviewed. The evidence obtained so far supports the fact that these fatty acids are good inhibitors of the L. donovani DNA topoisomerase IB enzyme (LdTopIB) and the potency of LdTopIB inhibition is chain length dependent. We also demonstrate the generality of the antiprotozoal activity of 2-HDA and 2-ODA against P. falciparum, and review our present knowledge of their inhibition of key P. falciparum enzymes such as PfFabZ, PfFabG, and PfFabI together with some possible modes of inhibition. Recent research by our group has also demonstrated that 2-ODA displays antineoplastic activity, specifically against the neuroblastoma SH-SY5Y cell line via lactate dehydrogenase (LDH) release, which is a cell death mechanism principally associated to necrosis. This is the first comprehensive review of the medicinal chemistry of this interesting group of acetylenic fatty acids. PMID:23727443

  4. Recent developments in the antiprotozoal and anticancer activities of the 2-alkynoic fatty acids.

    Science.gov (United States)

    Carballeira, Néstor M

    2013-01-01

    The 2-alkynoic fatty acids are an interesting group of synthetic compounds that display antimycobacterial, antifungal, anticancer, and pesticidal activities but their antiprotozoal activity has received little attention until recently. In this review we have summarized our present knowledge of the biomedical potential of the 2-hexadecynoic acid (2-HDA) and 2-octadecynoic acid (2-ODA) together with several mechanistic pieces of work attesting to the fact that these compounds, and their metabolites, are good fatty acid biosynthesis inhibitors. The antiprotozoal activity of 2-HDA and 2-ODA against Leishmania donovani and Plasmodium falciparum, parasites responsible for visceral leishmaniasis and malaria, respectively, is also reviewed. The evidence obtained so far supports the fact that these fatty acids are good inhibitors of the L. donovani DNA topoisomerase IB enzyme (LdTopIB) and the potency of LdTopIB inhibition is chain length dependent. We also demonstrate the generality of the antiprotozoal activity of 2-HDA and 2-ODA against P. falciparum, and review our present knowledge of their inhibition of key P. falciparum enzymes such as PfFabZ, PfFabG, and PfFabI together with some possible modes of inhibition. Recent research by our group has also demonstrated that 2-ODA displays antineoplastic activity, specifically against the neuroblastoma SH-SY5Y cell line via lactate dehydrogenase (LDH) release, which is a cell death mechanism principally associated to necrosis. This is the first comprehensive review of the medicinal chemistry of this interesting group of acetylenic fatty acids. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Phylogenetic Tree Analysis of the Cold-Hot Nature of Traditional Chinese Marine Medicine for Possible Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Xianjun Fu

    2017-01-01

    Full Text Available Traditional Chinese Marine Medicine (TCMM represents one of the medicinal resources for research and development of novel anticancer drugs. In this study, to investigate the presence of anticancer activity (AA displayed by cold or hot nature of TCMM, we analyzed the association relationship and the distribution regularity of TCMMs with different nature (613 TCMMs originated from 1,091 species of marine organisms via association rules mining and phylogenetic tree analysis. The screened association rules were collected from three taxonomy groups: (1 Bacteria superkingdom, Phaeophyceae class, Fucales order, Sargassaceae family, and Sargassum genus; (2 Viridiplantae kingdom, Streptophyta phylum, Malpighiales class, and Rhizophoraceae family; (3 Holothuroidea class, Aspidochirotida order, and Holothuria genus. Our analyses showed that TCMMs with closer taxonomic relationship were more likely to possess anticancer bioactivity. We found that the cluster pattern of marine organisms with reported AA tended to cluster with cold nature TCMMs. Moreover, TCMMs with salty-cold nature demonstrated properties for softening hard mass and removing stasis to treat cancers, and species within Metazoa or Viridiplantae kingdom of cold nature were more likely to contain AA properties. We propose that TCMMs from these marine groups may enable focused bioprospecting for discovery of novel anticancer drugs derived from marine bioresources.

  6. Anticancer potency of black sea cucumber (Holothuria atra) from Mentawai Islands, Indonesia

    OpenAIRE

    Mieke Hemiawati Satari; Utmi Arma; Syafruddin Ilyas; Dian Handayani

    2017-01-01

    ABSTRACT Introduction: The source of bioactive compounds believed to have strong anticancer potency is derived from sea cucumber. Black sea cucumber (Holothuria atra) is a dominant species in Mentawai Islands, West Sumatera, Indonesia. Key factor compound that acts as anticancer in sea cucumber extract is tritepenoid also known as Frondoside A. The purpose of this study was to determine the effectiveness of the active compound taken from black sea cucumber as anticancer. Methods: Methods u...

  7. Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

    Directory of Open Access Journals (Sweden)

    Liu Y

    2016-07-01

    Full Text Available Yuling Liu,1,* Yingqi Xu,2,* Minghui Wu,3 Lijiao Fan,1 Chengwei He,2 Jian-Bo Wan,2 Peng Li,2 Meiwan Chen,2 Hui Li11Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 3Department of Cell Biology and Anatomy, School of Medicine, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Abstract: Mitoxantrone (MIT is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC50 value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines. In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy. Keywords: F68, vitamin E

  8. Antibacterial and anticancer activity of marine Streptomyces parvus: optimization and application

    Directory of Open Access Journals (Sweden)

    Hanan Abd-Elnaby

    2016-01-01

    Full Text Available A total of 17 actinomycetes were isolated and screened against five bacterial pathogens. Forty-one per cent of the isolates were active against the tested pathogens. The most potent isolate was identified as Streptomyces parvus by using a 16S rRNA sequence analysis. S. parvus produced active compound(s against a number of Gram negative and Gram positive bacteria. The obtained inhibition zones were 14, 19, 20 and 20 mm against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Aeromonas hydrophila, respectively. Moreover, the anticancer activity of S. parvus was tested against four different cell lines: human liver cancer cell line, mouse lymphoma cell line, breast cancer cell line and human colon cancer cell line. The inhibition activities were 53%, 56%, 57% and 42%, respectively. To achieve a maximum production of the bioactive compound, Plackett–Burman design was applied. The productivity increased up to 1.3-fold, when S. parvus was grown in optimized medium composed of: 10 g L−1 starch, 1.5 g L−1 KNO3, 0.75 g L−1 K2HPO4, 0.75 g L−1 MgSO4∙7H2O, 0.015 g L−1 FeSO4, 2 mL (103 colony-forming units mL−1 inoculum size with pH 8 for 7 d of incubation. The main constitutes of S. parvus crude extract were determined by gas–liquid chromatography mass spectrometry. They were found to be ethane, 1,1-diethoxy; di-n-octyl phthalate; ethanol, 2,2-diethoxy; 9,12-octadecadienoic acid; methyl ester (E,E and benzoic acid.

  9. Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1,3-dihydropyridine, chromene and chromenopyridine moieties

    Directory of Open Access Journals (Sweden)

    Al-Said Mansour S

    2012-07-01

    Full Text Available Abstract Several new sulfonebiscompounds having a biologically active 1,2-dihydropyridine-2-one 3–19, acrylamide 20, chromene 21, 22 and chromenopyridine 23, 24 moieties were synthesized and evaluated as potential anticancer agents. The structures of the products were confirmed via elemental analyses and spectral data. The screening tests showed that many of the biscompounds obtained exhibited good anticancer activity against human breast cell line (MCF7 comparable to doxorubicin which was used as reference drug. Compounds 11, 17 and 24 showed IC50 values 35.40 μM, 29.86 μM and 30.99 μM, respectively. In order to elucidate the mechanism of action of the synthesized compounds as anticancer agents, docking on the active site of farnesyltransferase and arginine methyltransferase was also performed and good results were obtained.

  10. Theoretical Study of Phosphoethanolamine: A Synthetic Anticancer Agent with Broad Antitumor Activity

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    Vitor Prates Lorenzo

    2016-01-01

    Full Text Available Cancer is a major public health problem with limited success of available treatments, pointing to the need for new strategies to be developed. Phosphoethanolamine exhibits broad antitumor activity in a variety of tumor cells and potent inhibitor effects on tumor progress in vivo. Once-used organophosphates inhibit acetylcholinesterase (AChE, resulting in toxic effects to the user. As this group is present in phosphoethanolamine, we perform prediction of the in silico metabolism of phosphoethanolamine and submit this series to a docking study on AChE. A total of 10 metabolites were indicated by the prediction, including ammonia and hydroxylamine, which were not included in the study. Using a group of 8 organophosphorus whose pIC50 values ranged from 5.92 to 9.47 as template, we observed that no compound present in the phosphoethanolamine series had a binding energy lower than that of organophosphorus, suggesting that the series has low inhibitory power on AChE. In light of this, we conclude that phosphoethanolamine and its predicted metabolites do not significantly inhibit AChE to cause a cholinergic crisis. This finding highlights the importance of investigating this compound as lead for potential anticancer agents.

  11. Functional Characterisation of Anticancer Activity in the Aqueous Extract of Helicteres angustifolia L. Roots.

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    Kejuan Li

    Full Text Available Helicteres angustifolia L. is a shrub that forms a common ingredient of several cancer treatment recipes in traditional medicine system both in China and Laos. In order to investigate molecular mechanisms of its anticancer activity, we prepared aqueous extract of Helicteres angustifolia L. Roots (AQHAR and performed several in vitro assays using human normal fibroblasts (TIG-3 and osteosarcoma (U2OS. We found that AQHAR caused growth arrest/apoptosis of U2OS cells in a dose-dependent manner. It showed no cytotoxicity to TIG-3 cells at doses up to 50 μg/ml. Biochemical, imaging and cell cycle analyses revealed that it induces ROS signaling and DNA damage response selectively in cancer cells. The latter showed upregulation of p53, p21 and downregulation of Cyclin B1 and phospho-Rb. Furthermore, AQHAR-induced apoptosis was mediated by increase in pro-apoptotic proteins including cleaved PARP, caspases and Bax. Anti-apoptotic protein Bcl-2 showed decrease in AQHAR-treated U2OS cells. In vivo xenograft tumor assays in nude mice revealed dose-dependent suppression of tumor growth and lung metastasis with no toxicity to the animals suggesting that AQHAR could be a potent and safe natural drug for cancer treatment.

  12. The acute toxicity of ethanol extract from irradiated Temulawak (curcuma xanthorrizha roxb.) which have anticancer activity

    International Nuclear Information System (INIS)

    Ermin Katrin; Susanto; Hendig Winarno

    2011-01-01

    Pasteurization of herbs and herbal medicinal products have been carried out by several herbal industries, but information about the safety of irradiated herbal medicine is still a little, even the influence of gamma irradiation for pasteurization purpose on the toxicity of crude Temulawak has never been investigated. The ethanol extract of Curcuma xanthorrizha Roxb. has cytotoxic activity which potential as an anticancer. In this research, the acute toxicity tests were carried out to the ethanol extract from Curcuma xanthorrizha without irradiation and irradiated with doses of 5 and 10 kGy. The acute toxicity tests of ethanol extract were conducted in mice by observing the effect of extracts on animal behavior (pharmacologic profile) after a single dose of test material, the development of animal body weight and death every day for 14 days and observed several organ weights on day 14. Acute toxicity test results after administration of extracts on male and female mice a dose up to 7500 mg/kg body weight (BW) showed that no deaths and no significant toxic effect, so that the ethanol extract of Curcuma xanthorrizha without irradiation and irradiated with doses of 5 and 10 kGy can be declared safe. Thus LD 50 from ethanol extract of Curcuma xanthorrizha without irradiation and irradiated (5 and 10 kGY) in mice was greater than 7500 mg/kg body weight. (author)

  13. Synthesis, structural, solubility and anticancer activity studies of salts using nucleobases and sulfonic acids coformer

    Science.gov (United States)

    Singh, Neetu; Singh, Udai P.; Nikhil, Kumar; Roy, Partha; Singh, Hariji

    2017-10-01

    The reactions of natural and unnatural nucleobases (cytosine (Cyt), adenine (Ade), 5-aminouracil (AU) and caffeine (Caff)) with sulfonic acids coformer (1,5-naphthalenedisulfonic acid, NDSA; 5-sulfosalicylic acid, SSA) resulted in the formation of salts viz. [NDSA.Cyt] (1), [NDSA.Ade] (2), [NDSA.AU] (3), [NDSA.Caff] (4), [SSA.Cyt] (5), [SSA.Ade] (6), [SSA.AU] (7), and [SSA.Caff] (8). The structural analysis revealed that salts 1, 4, 6 and 7 have intermolecular interactions between adjacent nucleobases which form two different homodimer shown in R22 (8) motif and assembled via complementary Nsbnd H⋯O and Nsbnd H⋯N interactions. However, in all other salts an intermediate supramolecular synthon pattern was observed between nucleobases and sulfonic acids. The lattice energy was also calculated by DFT to investigate whether salts were thermodynamically more stable than its coformer. The same was further confirmed by differential scanning calorimetry-thermogravimetric (DSC-TG) analysis. The anticancer activity study of individual nucleobases and their NDSA salts were also performed on human breast (MCF-7) and lung (A 549) cancer cell. The salts formation of nucleobases with sulfonic acids improved their solubility, thereby demonstrating up to 8-fold increase in solubility of nucleobases.

  14. Relationship between Oversulfation and Conformation of Low and High Molecular Weight Fucoidans and Evaluation of Their in Vitro Anticancer Activity

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    Myoung Lae Cho

    2010-12-01

    Full Text Available Low and high molecular weight fucoidans (F5-30K and F>30K were chemically modified through the addition of sulfate groups, and the effect of oversulfation on the in vitro anticancer activity was investigated. After the addition of sulfate groups, a considerable increase of 35.5 to 56.8% was observed in the sulfate content of the F5-30K fraction, while the sulfate content of the F>30K fraction increased to a lesser extent (from 31.7 to 41.2%. Significant differences in anticancer activity were observed between the oversulfated F5–30K and F>30K fractions, with activities of 37.3–68.0% and 20.6–35.8%, respectively. This variation in the anticancer activity of oversulfated fucoidan derivatives was likely due to differences in their sulfate content. The results suggest that the molecular conformation of these molecules is closely related to the extent of sulfation in the fucan backbones and that the sulfates are preferably substituted when the fucoidan polymers are in a loose molecular conformation.

  15. (−-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer

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    Joan Crous-Masó

    2018-05-01

    Full Text Available (−-Epigallocatechin 3-gallate (EGCG is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN, which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC cells. All compounds displayed moderate to high cytotoxicity and significantly blocked FASN activity, monoesters M1 and M2 being more potent inhibitors than diesters. Interestingly, G28, M1, and M2 also diminished FASN protein expression levels, but only monoesters M1 and M2 induced apoptosis. Our results indicate that FASN inhibition by such polyphenolic compounds could be a new strategy in TNBC treatment, and highlight the potential anticancer activities of monoesters. Thus, G28, G37, G56, and most importantly M1 and M2, are anticancer candidates (alone or in combination to be further characterized in vitro and in vivo.

  16. (-)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer.

    Science.gov (United States)

    Crous-Masó, Joan; Palomeras, Sònia; Relat, Joana; Camó, Cristina; Martínez-Garza, Úrsula; Planas, Marta; Feliu, Lidia; Puig, Teresa

    2018-05-11

    (-)-Epigallocatechin 3-gallate (EGCG) is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN), which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC) cells. All compounds displayed moderate to high cytotoxicity and significantly blocked FASN activity, monoesters M1 and M2 being more potent inhibitors than diesters. Interestingly, G28, M1, and M2 also diminished FASN protein expression levels, but only monoesters M1 and M2 induced apoptosis. Our results indicate that FASN inhibition by such polyphenolic compounds could be a new strategy in TNBC treatment, and highlight the potential anticancer activities of monoesters. Thus, G28, G37, G56, and most importantly M1 and M2, are anticancer candidates (alone or in combination) to be further characterized in vitro and in vivo.

  17. Anticancer activity of Nigella sativa (black seed) and its relationship with the thermal processing and quinone composition of the seed.

    Science.gov (United States)

    Agbaria, Riad; Gabarin, Adi; Dahan, Arik; Ben-Shabat, Shimon

    2015-01-01

    The traditional preparation process of Nigella sativa (NS) oil starts with roasting of the seeds, an allegedly unnecessary step that was never skipped. The aims of this study were to investigate the role and boundaries of thermal processing of NS seeds in the preparation of therapeutic extracts and to elucidate the underlying mechanism. NS extracts obtained by various seed thermal processing methods were investigated in vitro for their antiproliferative activity in mouse colon carcinoma (MC38) cells and for their thymoquinone content. The effect of the different methods of thermal processing on the ability of the obtained NS oil to inhibit the nuclear factor kappa B (NF-κB) pathway was then investigated in Hodgkin's lymphoma (L428) cells. The different thermal processing protocols yielded three distinct patterns: heating the NS seeds to 50°C, 100°C, or 150°C produced oil with a strong ability to inhibit tumor cell growth; no heating or heating to 25°C had a mild antiproliferative effect; and heating to 200°C or 250°C had no effect. Similar patterns were obtained for the thymoquinone content of the corresponding oils, which showed an excellent correlation with the antiproliferative data. It is proposed that there is an oxidative transition mechanism between quinones after controlled thermal processing of the seeds. While NS oil from heated seeds delayed the expression of NF-κB transcription, non-heated seeds resulted in only 50% inhibition. The data indicate that controlled thermal processing of NS seeds (at 50°C-150°C) produces significantly higher anticancer activity associated with a higher thymoquinone oil content, and inhibits the NF-κB signaling pathway.

  18. Entrapment of curcumin into monoolein-based liquid crystalline nanoparticle dispersion for enhancement of stability and anticancer activity

    Directory of Open Access Journals (Sweden)

    Baskaran R

    2014-06-01

    Full Text Available Rengarajan Baskaran,1 Thiagarajan Madheswaran,2 Pasupathi Sundaramoorthy,1 Hwan Mook Kim,1 Bong Kyu Yoo1 1College of Pharmacy, Gachon University, Incheon, South Korea; 2College of Pharmacy Yeungnam University, Gyeongsan, South Korea Abstract: Despite the promising anticancer potential of curcumin, its therapeutic application has been limited, owing to its poor solubility, bioavailability, and chemical fragility. Therefore, various formulation approaches have been attempted to address these problems. In this study, we entrapped curcumin into monoolein (MO-based liquid crystalline nanoparticles (LCNs and evaluated the physicochemical properties and anticancer activity of the LCN dispersion. The results revealed that particles in the curcumin-loaded LCN dispersion were discrete and monodispersed, and that the entrapment efficiency was almost 100%. The stability of curcumin in the dispersion was surprisingly enhanced (about 75% of the curcumin survived after 45 days of storage at 40°C, and the in vitro release of curcumin was sustained (10% or less over 15 days. Fluorescence-activated cell sorting (FACS analysis using a human colon cancer cell line (HCT116 exhibited 99.1% fluorescence gating for 5 µM curcumin-loaded LCN dispersion compared to 1.36% for the same concentration of the drug in dimethyl sulfoxide (DMSO, indicating markedly enhanced cellular uptake. Consistent with the enhanced cellular uptake of curcumin-loaded LCNs, anticancer activity and cell cycle studies demonstrated apoptosis induction when the cells were treated with the LCN dispersion; however, there was neither noticeable cell death nor significant changes in the cell cycle for the same concentration of the drug in DMSO. In conclusion, entrapping curcumin into MO-based LCNs may provide, in the future, a strategy for overcoming the hurdles associated with both the stability and cellular uptake issues of the drug in the treatment of various cancers. Keywords: liquid

  19. Impact of aromaticity on anticancer activity of polypyridyl ruthenium(II) complexes: synthesis, structure, DNA/protein binding, lipophilicity and anticancer activity.

    Science.gov (United States)

    Čanović, Petar; Simović, Ana Rilak; Radisavljević, Snežana; Bratsos, Ioannis; Demitri, Nicola; Mitrović, Marina; Zelen, Ivanka; Bugarčić, Živadin D

    2017-10-01

    With the aim of assessing how the aromaticity of the inert chelating ligand can influence the activity of ruthenium(II) polypyridyl complexes, two new monofunctional ruthenium(II) complexes, [Ru(Cl-Ph-tpy)(phen)Cl]Cl (1) and [Ru(Cl-Ph-tpy)(o-bqdi)Cl]Cl (2) (where Cl-Ph-tpy = 4'-(4-chlorophenyl)-2,2':6',2″-terpyridine, phen = 1,10-phenanthroline, o-bqdi = o-benzoquinonediimine), were synthesized. All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR, XRD). Their chemical behavior in aqueous solution was studied by UV-Vis and NMR spectroscopy showing that both compounds are relatively labile leading to the formation of the corresponding aqua species 1a and 2a. 1 H NMR spectroscopy studies performed on complexes 1 and 2 demonstrated that after the hydrolysis of the Cl ligand, they are capable to interact with guanine derivatives (i.e., 9-methylguanine (9MeG) and 5'-GMP) through the N7, forming monofunctional adduct. The kinetics and the mechanism of the reaction of complexes 1 and 2 with the biologically more relevant 5'-GMP ligand were studied by UV-Vis spectroscopy. DNA/protein interactions of the complexes have been examined by photophysical studies, which demonstrated a bifunctional binding mode of the complexes with DNA and the complexes strongly quench the fluorescence intensity of bovine serum albumin (BSA) through the mechanism of both static and dynamic quenching. Complexes 1 and 2 strongly induced apoptosis of treated cancer cells with high percentages of apoptotic cells and negligible percentage of necrotic cells. In addition, both ruthenium complexes decreased Bcl-2/Bax ratio causing cytochrome c mitochondrial release, the activation of caspase-3 and induction of apoptosis.

  20. Enhanced anticancer activity and circumvention of resistance mechanisms by novel polymeric/ phospholipidic nanocarriers of doxorubicin.

    Science.gov (United States)

    Senkiv, Y; Riabtseva, A; Heffeter, P; Boiko, N; Kowol, C R; Jungwith, U; Shlyakhtina, Y; Garasevych, S G; Mitina, N; Berger, W; Zaichenko, A; Stoika, R

    2014-07-01

    Severe toxic side effects and drug resistance are the major limitations of doxorubicin (Dox), one of the most potent anticancer agents in clinical use. Nanocarrier preparations offer the opportunity to overcome these drawbacks, which is reflected in the clinical approval of two liposomal Dox preparations. Additionally, there are many attempts to enhance the activity of Dox against multi-drug resistant (MDR) cancer cells. However, most of these strategies resulted in the increased uptake of Dox in resistant cells, only, while it remained unchanged in chemo-sensitive cells. Here, we present a new polymeric-phospholipidic hybrid delivery system which distinctly enhanced the accumulation and activity of Dox in all tested cancer cell lines including several MDR cell models. Notably, the resistance levels against Dox were reduced from about 6-fold to about 2-fold. Moreover, the new nanocarriers were shown to rapidly (within 10 min) and effectively transport Dox into resistant as well as sensitive cancer cells. Consequently, treatment with the new Dox-containing nanocarriers resulted in effective cell cycle arrest in G2/M phase and ROS-induced cell death induction. Finally, the new nanocarriers were tested against NK/Ly lymphoma and L1210 leukemia cells in vivo. In both cell models, the nanoformulation of Dox resulted in 100% cured animals already at low concentrations (0.1 mg/kg), while free Dox solely extended survival time. This indicates that the incorporation of phospholipids into PEGylated polymeric nanocarriers is a promising strategy to enhance efficacy and reduce toxicity of Dox treatment against both sensitive and resistant cancer models in vitro and in vivo.

  1. Hierarchical mesosilicalite nanoformulation integrated with cisplatin exhibits target-specific efficient anticancer activity

    Science.gov (United States)

    Jermy, B. Rabindran; Acharya, Sadananda; Ravinayagam, Vijaya; Alghamdi, Hajer Saleh; Akhtar, Sultan; Basuwaidan, Rehab S.

    2018-04-01

    Hierarchically structured zeolitic ZSM-5 and meso MCM-41 interlinked domain had an impeccable use as catalysis in many applications. The aim of the study was to develop a new drug delivery nanoformulation, specifically, cisplatin/mesosilicalite using top-down approach for cancer therapy. Hierarchical mesosilicalite with variable porosity was synthesized using alkaline molar solution (0.2 and 0.7 M NaOH) and was loaded with cisplatin through equilibrium adsorption technique. Physico-chemical properties of the nanoformulation (IAUM-56—Imam Abdulrahman Bin Faisal University Mesosilicalite-56) were characterized using X-ray diffraction, surface area analysis (BET), Fourier transformed infrared spectroscopy (FT-IR), diffuse reflectance UV-Vis spectroscopy, and transmission electron microscopy. Drug release study and anticancer activity were assayed on HeLa and MCF7 cancer cells using MTT assay. X-ray diffraction pattern showed interrelated meso- and microphases, while BET analysis revealed considerable mesoporosity formation with a remodulation of isotherm hysteresis indicating the presence of hierarchical pores. FT-IR showed the presence of nanozeolitic subunits into mesostructure with a band at about 550 cm-1. IAUM-56 demonstrated high cytotoxic activity against HeLa cancer cells with an LC50 of 0.02 mg/ml, MCF7 cancer cells with an LC50 of 0.05 mg/ml, and less toxic to normal fibroblast cells with an LC50 of approximately ten times higher at 0.5 mg/ml. Overall, IAUM-56 showed a high rate of sustained release of cisplatin imparting target specific cytotoxic effect against tumor cells with at least tenfold lower toxicity on normal fibroblast cells. Our nanoformulation has the potential use in cancer therapy as a targeted drug delivery system.

  2. Green synthesis and characterization of zinc oxide nanoparticle using insulin plant (Costus pictus D. Don) and investigation of its antimicrobial as well as anticancer activities

    Science.gov (United States)

    Suresh, Joghee; Pradheesh, Ganeshan; Alexramani, Vincent; Sundrarajan, Mahalingam; Hong, Sun Ig

    2018-03-01

    In this work we aim to synthesize biocompatible ZnO nanoparticles from the zinc nitrate via green process using leaf extracts of the Costus pictus D. Don medicinal plant. FTIR studies confirm the presence of biomolecules and metal oxides. X-ray diffraction (XRD) structural analysis reveals the formation of pure hexagonal phase structures of ZnO nanoparticles. The surface morphologies of ZnO nanoparticles observed under a scanning electron microscope (SEM) suggest that most ZnO crystallites are hexagonal. EDX analysis confirms the presence of primarily zinc and oxygen. TEM images show that biosynthesized zinc oxide nanoparticles are hexagonal and spherical. The plausible formation mechanisms of zinc oxide nanoparticles are also predicted. The biosynthesized zinc oxide nanoparticles exhibit strong antimicrobial behavior against bacterial and fungal species when employing the agar diffusion method. Synthesized ZnO nanoparticles exhibit anticancer activity against Daltons lymphoma ascites (DLA) cells as well as antimicrobial activity against some bacterial and fungal strains.

  3. New bioactive silver(I) complexes: Synthesis, characterization, anticancer, antibacterial and anticarbonic anhydrase II activities

    Science.gov (United States)

    Ozdemir, Ummuhan O.; Ozbek, Neslihan; Genc, Zuhal Karagoz; İlbiz, Firdevs; Gündüzalp, Ayla Balaban

    2017-06-01

    Silver(I) complexes of alkyl sulfonic acide hydrazides were newly synthesized as homologous series. Methanesulfonic acide hydrazide (L1), ethanesulfonic acide hydrazide (L2), propanesulfonic acide hydrazide (L3) and butanesulfonic acide hydrazide (L4) were used for complexation with Ag(I) ions. The silver complexes obtained in the mol ratio of 1:2 have the structural formula as Ag(L1)2NO3 (I), Ag(L2)2NO3 (II), Ag(L3)2NO3(III), (Ag(L4)2NO3 (IV). The Ag(I) complexes exhibit distorted linear two-fold coordination in [AgL2]+ cations with uncoordinated nitrates. Ligands are chelated with silver(I) ions through unsubstituted primary nitrogen in hydrazide group. Ag(I) complexes were characterized by using elemental analysis, spectroscopic methods (FT-IR, LC-MS), magnetic susceptibility and conductivity measurements. Silver(I) complexes were optimized using PBEPBE/LanL2DZ/DEF2SV basic set performed by DFT method with the Gaussian 09 program package. The geometrical parameters, frontier molecular orbitals (HOMOs and LUMOs) and molecular electrostatic potential (MEP) mapped surfaces of the optimized geometries were also determined by this quantum set. The anticancer activities of silver(I) complexes on MCF-7 human breast cancer cell line were investigated by comparing IC50 values. The antibacterial activities of complexes were studied against Gram positive bacteria; S. aureus ATCC 6538, B. subtilis ATCC 6633, B. cereus NRRL-B-3711, E. faecalis ATCC 29212 and Gram negative bacteria; E. coli ATCC 11230, P. aeruginosa ATCC 15442, K. pneumonia ATCC 70063 by using disc diffusion method. The inhibition activities of Ag(I) complexes on carbonic anhydrase II enzyme (hCA II) were also investigated by comparing IC50 and Ki values. The biological activity screening shows that Ag(I) complex of butanesulfonicacidehydrazide (IV) has the highest activity against tested breast cancer cell lines MCF-7, Gram positive/Gram negative bacteria and carbonic anhydrase II (hCA II) isoenzyme.

  4. Isolation of eugenyl β-primeveroside from Camellia sasanqua and its anticancer activity in PC3 prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Chun-Chieh Wang

    2016-01-01

    Full Text Available Most studies of tea trees have focused on their ornamental properties, there are fewer published studies on their medical values. The purpose of this study was to compare the chemical constituents and the biological potential of the water extract of leaves in eight species of Camellia including Camellia sinensis. Among eight Camellia species, Camellia sasanqua showed potent anticancer activities in prostate cancer PC3 cells. In addition to catechins, the major component, eugenyl β-primeveroside was detected in C. sasanqua. Eugenyl β-primeveroside blocked the progression of cell cycle at G1 phase by inducing p53 expression and further upregulating p21 expression. Moreover, eugenyl β-primeveroside induced apoptosis in PC3 prostate cancer cells. Our results suggest that C. sasanqua may have anticancer potential.

  5. A nanocomplex of Cu(II) with theophylline drug; synthesis, characterization, and anticancer activity against K562 cell line

    Science.gov (United States)

    Sahlabadi, Maryam; Daryanavard, Marzieh; Hadadzadeh, Hassan; Amirghofran, Zahra

    2018-03-01

    A new mononuclear of copper (II), [Cu(theophylline)2(H2O)3]·2H2O, has been synthesized by reaction of theophylline (1,3-dimethyl-7H-purine-2,6-dione) with copper (II) nitrate in water. Further, its nanocomplex has been prepared through the three different methods including sonication, grinding, and a combination thereof, sonication-grinding. The prepared nanocomplex was characterized using different techniques including FT-IR, UV-Vis, X-ray diffraction (XRD) analysis, and field-emission scanning electron microscopy (FE-SEM). Moreover, the anticancer activity of the precursor complex, nanocomplex, free theophylline ligand, and the starting copper salt (Cu(NO3)2·3H2O) was investigated against the K562 cell line. The results show that the nanocomplex is an effective nano metal-based anticancer agent with IC50 = 11.7 μM.

  6. Synthesis of flexirubin-mediated silver nanoparticles using Chryseobacterium artocarpi CECT 8497 and investigation of its anticancer activity

    International Nuclear Information System (INIS)

    Venil, Chidambaram Kulandaisamy; Sathishkumar, Palanivel; Malathi, Mahalingam; Usha, Rajamanickam; Jayakumar, Rajarajeswaran; Yusoff, Abdull Rahim Mohd; Ahmad, Wan Azlina

    2016-01-01

    In this work, the synthesis of silver nanoparticles from a pigment produced by a recently-discovered bacterium, Chryseobacterium artocarpi CECT 8497, was achieved, followed by an investigation of its anticancer properties. The bacterial pigment was identified as flexirubin following NMR ("1H NMR and "1"3C NMR), UV–Vis, and LC–MS analysis. An aqueous silver nitrate solution was treated with isolated flexirubin to produce silver nanoparticles. The synthesised silver nanoparticles were subsequently characterised by UV–Vis spectroscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), X-Ray Diffraction (XRD), and Fourier Transform Infrared (FTIR) Spectroscopy methodologies. Furthermore, the anticancer effects of synthesised silver nanoparticles in a human breast cancer cell line (MCF-7) were evaluated. The tests showed significant cytotoxicity activity of the silver nanoparticles in the cultured cells, with an IC50 value of 36 μg mL"−"1. This study demonstrates that silver nanoparticles, synthesised from flexirubin from C. artocarpi CECT 8497, may have potential as a novel chemotherapeutic agent. - Highlights: • First report on flexirubin mediated silver nanoparticles • Silver nanoparticles synthesised using flexirubin • Flexirubin mediated silver nanoparticles found to possess in vitro anti-cancer activity

  7. Synthesis of flexirubin-mediated silver nanoparticles using Chryseobacterium artocarpi CECT 8497 and investigation of its anticancer activity

    Energy Technology Data Exchange (ETDEWEB)

    Venil, Chidambaram Kulandaisamy, E-mail: ckvenil@gmail.com [Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru (Malaysia); Sathishkumar, Palanivel [Centre for Environmental Sustainability and Water Security (IPASA), Research Institute for Sustainable Environment (RISE), Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru (Malaysia); Malathi, Mahalingam [Department of Chemistry, Bannari Amman Institute of Technology, Sathyamangalam 638 401, Tamil Nadu (India); Usha, Rajamanickam [Department of Microbiology, Karpagam University, Coimbatore 641 023, Tamil Nadu (India); Jayakumar, Rajarajeswaran [Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Yusoff, Abdull Rahim Mohd [Centre for Environmental Sustainability and Water Security (IPASA), Research Institute for Sustainable Environment (RISE), Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru (Malaysia); Ahmad, Wan Azlina, E-mail: azlina@kimia.fs.utm.my [Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor Bahru (Malaysia)

    2016-02-01

    In this work, the synthesis of silver nanoparticles from a pigment produced by a recently-discovered bacterium, Chryseobacterium artocarpi CECT 8497, was achieved, followed by an investigation of its anticancer properties. The bacterial pigment was identified as flexirubin following NMR ({sup 1}H NMR and {sup 13}C NMR), UV–Vis, and LC–MS analysis. An aqueous silver nitrate solution was treated with isolated flexirubin to produce silver nanoparticles. The synthesised silver nanoparticles were subsequently characterised by UV–Vis spectroscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), X-Ray Diffraction (XRD), and Fourier Transform Infrared (FTIR) Spectroscopy methodologies. Furthermore, the anticancer effects of synthesised silver nanoparticles in a human breast cancer cell line (MCF-7) were evaluated. The tests showed significant cytotoxicity activity of the silver nanoparticles in the cultured cells, with an IC50 value of 36 μg mL{sup −1}. This study demonstrates that silver nanoparticles, synthesised from flexirubin from C. artocarpi CECT 8497, may have potential as a novel chemotherapeutic agent. - Highlights: • First report on flexirubin mediated silver nanoparticles • Silver nanoparticles synthesised using flexirubin • Flexirubin mediated silver nanoparticles found to possess in vitro anti-cancer activity.

  8. Anticancer Properties of Capsaicin Against Human Cancer.

    Science.gov (United States)

    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

    There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Microwave-Assisted Synthesis of 3,5-Dibenzyl-4-amino-1,2,4-triazole and its Diazo Ligand, Metal Complexes Along with Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Anjali Jha

    2010-01-01

    Full Text Available Synthesis of 3,5-dibenzyl-4-amino-1,2,4-triazole was accomplished via a conventional method as well as microwave irradiation method, followed by diazotization and coupling with 2,4-pentanedione. The dinucleating ligand was isolated and complexed with Ni(II, Cu(II and Ru(III chlorides. These complexes were screened on Jurkat, Raji & PBMC cell lines for anticancer activity. Ruthenium complexes showed potential anticancer activities.

  10. Elevated p21-Activated Kinase 2 Activity Results in Anchorage-Independent Growth and Resistance to Anticancer Drug–Induced Cell Death

    Directory of Open Access Journals (Sweden)

    Jerry W. Marlin

    2009-03-01

    Full Text Available p21-Activated kinase 2 (PAK-2 seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death response. In this study, we present a role of elevated activity of full-length PAK-2 in anchorage-independent growth and resistance to anticancer drug–induced apoptosis of cancer cells. Hs578T human breast cancer cells that have low levels of PAK-2 activity were more sensitive to anticancer drug–induced apoptosis and showed higher levels of caspase activation of PAK-2 than MDA-MB435 and MCF-7 human breast cancer cells that have high levels of PAK-2 activity. To examine the role of elevated PAK-2 activity in breast cancer, we have introduced a conditionally active PAK-2 into Hs578T human breast cells. Conditional activation of PAK-2 causes loss of contact inhibition and anchorage-independent growth of Hs578T cells. Furthermore, conditional activation of PAK-2 suppresses activation of caspase 3, caspase activation of PAK-2, and apoptosis of Hs578T cells in response to the anticancer drug cisplatin. Our data suggest a novel mechanism by which full-length PAK-2 activity controls the apoptotic response by regulating levels of activated caspase 3 and thereby its own cleavage to the proapoptotic PAK-2p34 fragment. As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug–induced apoptosis.

  11. A one-pot laccase-catalysed synthesis of coumestan derivatives and their anticancer activity

    CSIR Research Space (South Africa)

    Qwebani-Ogunleye, Tozama

    2016-12-01

    Full Text Available screened against renal TK10, melanoma UACC62 and breast MCF7 cancer cell-lines and the GI50, TGI and LC50 values determined. Anticancer screening showed that the cytostatic effects of the coumestans were most effective against the melanoma UACC62 and breast...

  12. Anti-Cancer Efficacy of Silybin Derivatives - A Structure-Activity Relationship

    Czech Academy of Sciences Publication Activity Database

    Agarwal, Ch.; Wadhwa, R.; Deep, G.; Biedermann, David; Gažák, Radek; Křen, Vladimír; Agarwal, R.

    2013-01-01

    Roč. 8, č. 3 (2013), e00074 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) ME10027 Institutional support: RVO:61388971 Keywords : Silybin * silibinin * anti-cancer efficacy Subject RIV: CE - Biochemistry Impact factor: 3.534, year: 2013

  13. A Laccase-catalysed one-pot synthesis of aminonaphthoquinones and their anticancer activity

    CSIR Research Space (South Africa)

    Wellington, Kevin W

    2012-05-01

    Full Text Available of the primary amine and 1,4-naphthohydroquinone in succinate-lactate buffer and a co-solvent, dimethylformamide, under mild reaction conditions in a vessel open to air at pH 4.5 and pH 6.0. Anticancer screening showed that the aminonaphthoquinones exhibited...

  14. In Vitro Anticancer Activity of Ethanolic Extract of Euphorbia hirta (L ...

    African Journals Online (AJOL)

    In the present study, In vitro anticancer effects of Euphorbia hirta were investigated. The objectives of this study are to find the presence of secondary metabolites by preliminary phytochemical investigation and FTIR analysis in the Euphorbia hirta. Ethanolic leaf extract of Euphorbia hirta was tested for its cytotoxicity against ...

  15. Isolation of a 60 kDa protein with in vitro anticancer activity against ...

    African Journals Online (AJOL)

    Sea hares have greatly attracted the interest of all those investigating chemical defense substances. Most of these substances are low molecular weight compounds derived from algal diets. In vitro anticancer effect of a 60 kDa protein isolated from the purple fluid of Aplysia dactylomela on four human cancer cell lines was ...

  16. Sildenafil citrate improves the delivery and anticancer activity of doxorubicin formulations in a mouse model of breast cancer.

    Science.gov (United States)

    Greish, Khaled; Fateel, Maryam; Abdelghany, Sara; Rachel, Nanitha; Alimoradi, Houman; Bakhiet, Moiz; Alsaie, Ahmed

    2017-11-21

    Sildenafil is an approved drug for the treatment of erectile dysfunction. The drug exerts its action through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. In this work, we tested whether the aforementioned effects of sildenafil on tumour vasculatures could result in an improvement of anticancer drug concentration in tumour tissues and hence improves its anticancer effect. Sildenafil when added to doxorubicin showed synergistic anticancer activity against 4T1 breast cancer cells in vitro. Adding 1, 30 and 100 μM of Viagra to 1 μM of doxorubicin resulted in 1.8-fold, 6.2-fold and 21-fold statistically significant increases in its cytotoxic effect, respectively. As a result, 4T1 tumour-bearing mice showed up to 2.7-fold increase in drug concentrations of the fluorescent Dye DiI and doxorubicin in tumour tissues, as well as their nanoformulations. Animals treated with the combinations of both Sildenafil citrate and doxorubicin showed a statistically significant 4.7-fold reduction in tumour size compared to doxorubicin alone. This work highlights the effect of Sildenafil on tumour vasculatures and provides a rational for further testing the combination on breast cancer patients.

  17. Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting.

    Science.gov (United States)

    Layek, Buddhadev; Sadhukha, Tanmoy; Panyam, Jayanth; Prabha, Swayam

    2018-06-01

    Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor-targeting strategy that relies on engineering mesenchymal stem cells (MSC) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count, whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano-engineered MSCs resulted in greater than 9-fold higher AUC lung of PTX (1.5 μg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 μg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano-engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor-specific drug delivery and significantly improved anti-cancer efficacy of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196-206. ©2018 AACR . ©2018 American Association for Cancer Research.

  18. Novel anticancer activity of phloroglucinol against breast cancer stem-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Rae-Kwon; Uddin, Nizam [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Hyun, Jin-Won [College of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756 (Korea, Republic of); Kim, Changil [Department of Biotechnology, Konkuk University, Chungju 380-701 (Korea, Republic of); Suh, Yongjoon, E-mail: hiswork@hanmail.net [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae, E-mail: sj0420@hanyang.ac.kr [Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2015-08-01

    Poor prognosis of breast cancer patients is closely associated with metastasis and relapse. There is substantial evidence supporting that cancer stem-like cells (CSCs) are primarily responsible for relapse in breast cancer after anticancer treatment. However, there is a lack of suitable drugs that target breast cancer stem-like cells (BCSCs). Here, we report that phloroglucinol (PG), a natural phlorotannin component of brown algae, suppresses sphere formation, anchorage-independent colony formation and in vivo tumorigenicity. In line with these observations, treatment with PG also decreased CD44{sup +} cancer cell population as well as expression of CSC regulators such as Sox2, CD44, Oct4, Notch2 and β-catenin. Also, treatment with PG sensitized breast cancer cells to anticancer drugs such as cisplatin, etoposide, and taxol as well as to ionizing radiation. Importantly, PG inhibited KRAS and its downstream PI3K/AKT and RAF-1/ERK signaling pathways that regulate the maintenance of CSCs. Taken together, our findings implicate PG as a good candidate to target BCSCs and to prevent the disease relapse. - Highlights: • Phloroglucinol suppresses in vivo tumor formation. • Phloroglucinol sensitizes breast cancer cells to anticancer agents. • Phloroglucinol inhibits breast cancer stem-like cells. • Phloroglucinol inhibits PI3K/AKT and KRAS/RAF/ERK signaling pathways.

  19. Anticancer Activity of Toxins from Bee and Snake Venom-An Overview on Ovarian Cancer.

    Science.gov (United States)

    Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Arvătescu, Cristian Andrei; Ifteni, Petru; Pleş, Liana

    2018-03-19

    Cancer represents the disease of the millennium, a major problem in public health. The proliferation of tumor cells, angiogenesis, and the relationship between the cancer cells and the components of the extracellular matrix are important in the events of carcinogenesis, and these pathways are being used as targets for new anticancer treatments. Various venoms and their toxins have shown possible anticancer effects on human cancer cell lines, providing new perspectives in drug development. In this review, we observed the effects of natural toxins from bee and snake venom and the mechanisms through which they can inhibit the growth and proliferation of cancer cells. We also researched how several types of natural molecules from venom can sensitize ovarian cancer cells to conventional chemotherapy, with many toxins being helpful for developing new anticancer drugs. This approach could improve the efficiency of standard therapies and could allow the administration of decreased doses of chemotherapy. Natural toxins from bee and snake venom could become potential candidates for the future treatment of different types of cancer. It is important to continue these studies concerning therapeutic drugs from natural resource and, more importantly, to investigate their mechanism of action on cancer cells.

  20. In Silico Screening, Synthesis and In Vitro Evaluation of Some Quinazolinone and Pyridine Derivatives as Dihydrofolate Reductase Inhibitors for Anticancer Activity

    Directory of Open Access Journals (Sweden)

    A. G. Nerkar

    2009-01-01

    Full Text Available Dihydrofolate reductase (DHFR is the important target for anticancer drugs belonging to the class of antimetabolites as the enzyme plays important role in the de novo purine synthesis. We here report the in silico screening to obtain best fit molecules as DHFR inhibitors, synthesis of some ʻbest fitʼ quinazolinone from 2-phenyl-3-(substituted-benzilidine-amino quinazolinones (Quinazolinone Shiff's bases QSB1-5 and pyridine-4-carbohydrazide Shiff's bases (ISB1-5 derivatives and their in vitro anticancer assay. Synthesis of the molecules was performed using microwave assisted synthesis. The structures of these molecules were elucidated by IR and 1H-NMR. These compounds were then subjected for in vitro anticancer evaluation against five human cancer cell-lines for anticancer cyto-toxicity assay. Methotrexate (MTX was used as standard for this evaluation to give a comparable inhibition of the cell proliferation by DHFR inhibition. Placlitaxel, adriamycin and 5-fluoro-uracil were also used as standard to give a comparable activity of these compounds with other mechanism of anticancer activity. ISB3 (4-(N, N-dimethyl-amino-phenyl Schiff''s base derivative of pyridine carbohydrazide showed equipotent activity with the standards used in in vitro anticancer assay as per the NCI (National Cancer Institute guidelines.

  1. <strong>Fate of xenobiotic compounds and plants activity in reed bed sludge treatment strong>

    DEFF Research Database (Denmark)

    Chen, Xijuan; Pauli, Udo; Rehfus, Stefan

    different plants: bulrush (Typha), reed (Phragmites australis) and reed canary grass (Phalaris arundinacea) were planted into 12 containers with a size of 1m Х 1m X 1m which were builded with 20cm gravel and 50cm sludge to study the plants activity in sludge degradation process, 4 containers were left...

  2. Entrapment of curcumin into monoolein-based liquid crystalline nanoparticle dispersion for enhancement of stability and anticancer activity

    Science.gov (United States)

    Baskaran, Rengarajan; Madheswaran, Thiagarajan; Sundaramoorthy, Pasupathi; Kim, Hwan Mook; Yoo, Bong Kyu

    2014-01-01

    Despite the promising anticancer potential of curcumin, its therapeutic application has been limited, owing to its poor solubility, bioavailability, and chemical fragility. Therefore, various formulation approaches have been attempted to address these problems. In this study, we entrapped curcumin into monoolein (MO)-based liquid crystalline nanoparticles (LCNs) and evaluated the physicochemical properties and anticancer activity of the LCN dispersion. The results revealed that particles in the curcumin-loaded LCN dispersion were discrete and monodispersed, and that the entrapment efficiency was almost 100%. The stability of curcumin in the dispersion was surprisingly enhanced (about 75% of the curcumin survived after 45 days of storage at 40°C), and the in vitro release of curcumin was sustained (10% or less over 15 days). Fluorescence-activated cell sorting (FACS) analysis using a human colon cancer cell line (HCT116) exhibited 99.1% fluorescence gating for 5 μM curcumin-loaded LCN dispersion compared to 1.36% for the same concentration of the drug in dimethyl sulfoxide (DMSO), indicating markedly enhanced cellular uptake. Consistent with the enhanced cellular uptake of curcumin-loaded LCNs, anticancer activity and cell cycle studies demonstrated apoptosis induction when the cells were treated with the LCN dispersion; however, there was neither noticeable cell death nor significant changes in the cell cycle for the same concentration of the drug in DMSO. In conclusion, entrapping curcumin into MO-based LCNs may provide, in the future, a strategy for overcoming the hurdles associated with both the stability and cellular uptake issues of the drug in the treatment of various cancers. PMID:25061290

  3. Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines – in vitro studies [Corrigendum

    Directory of Open Access Journals (Sweden)

    Legut M

    2015-09-01

    Full Text Available Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines – in vitro studies [Corrigendum]Legut M, Lipka D, Filipczak N, et al. Int J Nanomedicine. 2014;9:653–668.The authors advise the Acknowledgment on page 666 is missing the final sentence:This study was supported by: the Wrocław Research Centre EIT+ under the Biotechnologies and Advanced Medical Technologies project; BioMed (POIG.01.01.02-02-003/08, financed by the European Regional Development Fund (Operational Programme Innovative Economy, 1.1.2 #8221.Read the original article

  4. Efficacy, safety and anticancer activity of protein nanoparticle-based delivery of doxorubicin through intravenous administration in rats.

    Directory of Open Access Journals (Sweden)

    Kishore Golla

    Full Text Available Doxorubicin is a potent anticancer drug and a major limiting factor that hinders therapeutic use as its high levels of systemic circulation often associated with various off-target effects, particularly cardiotoxicity. The present study focuses on evaluation of the efficacy of doxorubicin when it is loaded into the protein nanoparticles and delivered intravenously in rats bearing Hepatocellular carcinoma (HCC. The proteins selected as carrier were Apotransferrin and Lactoferrin, since the receptors for these two proteins are known to be over expressed on cancer cells due to their iron transport capacity.Doxorubicin loaded apotransferrin (Apodoxonano and lactoferrin nanoparticles (Lactodoxonano were prepared by sol-oil chemistry. HCC in the rats was induced by 100 mg/l of diethylnitrosamine (DENA in drinking water for 8 weeks. Rats received 5 doses of 2 mg/kg drug equivalent nanoparticles through intravenous administration. Pharmacokinetics and toxicity of nanoformulations was evaluated in healthy rats and anticancer activity was studied in DENA treated rats. The anticancer activity was evaluated through counting of the liver nodules, H & E analysis and by estimating the expression levels of angiogenic and antitumor markers.In rats treated with nanoformulations, the numbers of liver nodules were found to be significantly reduced. They showed highest drug accumulation in liver (22.4 and 19.5 µg/g. Both nanoformulations showed higher localization compared to doxorubicin (Doxo when delivered in the absence of a carrier. Higher amounts of Doxo (195 µg/g were removed through kidney, while Apodoxonano and Lactodoxonano showed only a minimal amount of removal (<40 µg/g, suggesting the extended bioavailability of Doxo when delivered through nanoformulation. Safety analysis shows minimal cardiotoxicity due to lower drug accumulation in heart in the case of nanoformulation.Drug delivery through nanoformulations not only minimizes the cardiotoxicity of

  5. The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity.

    Science.gov (United States)

    Wagner, Jessica; Kline, Christina Leah; Pottorf, Richard S; Nallaganchu, Bhaskara Rao; Olson, Gary L; Dicker, David T; Allen, Joshua E; El-Deiry, Wafik S

    2014-12-30

    We previously identified TRAIL-inducing compound 10 (TIC10), also known as NSC350625 or ONC201, from a NCI chemical library screen as a small molecule that has potent anti-tumor efficacy and a benign safety profile in preclinical cancer models. The chemical structure that was originally published by Stahle, et. al. in the patent literature was described as an imidazo[1,2-a]pyrido[4,3-d]pyrimidine derivative. The NCI and others generally accepted this as the correct structure, which was consistent with the mass spectrometry analysis outlined in the publication by Allen et. al. that first reported the molecule's anticancer properties. A recent publication demonstrated that the chemical structure of ONC201 material from the NCI is an angular [3,4-e] isomer of the originally disclosed, linear [4,3-d] structure. Here we confirm by NMR and X-ray structural analysis of the dihydrochloride salt form that the ONC201 material produced by Oncoceutics is the angular [3,4-e] structure and not the linear structure originally depicted in the patent literature and by the NCI. Similarly, in accordance with our biological evaluation, the previously disclosed anti-cancer activity is associated with the angular structure and not the linear isomer. Together these studies confirm that ONC201, produced by Oncoceutics or obtained from the NCI, possesses an angular [3,4-e] structure that represents the highly active anti-cancer compound utilized in prior preclinical studies and now entering clinical trials in advanced cancers.

  6. Green synthesis, characterization, and anticancer activity of hyaluronan/zinc oxide nanocomposites

    Directory of Open Access Journals (Sweden)

    Namvar F

    2016-07-01

    were treated with HA/ZnO nanocomposite. At 72 hours of treatment, the half maximal inhibitory concentration (IC50 value via the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay was 10.8±0.3 µg/mL, 15.4±1.2 µg/mL, 12.1±0.9 µg/mL, and 6.25±0.5 µg/mL for the PANC-1, CaOV-3, COLO-205, and HL-60 cells, respectively, showing that the composite is most toxic to the HL-60 cells. On the other hand, HA/ZnO nanocomposite treatment for 72 hours did not cause toxicity to the normal human lung fibroblast (MRC-5 cell line. Using fluorescent dyes and flow cytometry analysis, HA/ZnO nanocomposite caused G2/M cell cycle arrest and stimulated apoptosis-related increase in caspase-3 and -7 activities of the HL-60 cells. Thus, the study shows that the HA/ZnO nanocomposite produced through green synthesis has great potential to be developed into an efficacious therapeutic agent for cancers. Keywords: green synthesis, hyaluronan, zinc oxide nanocomposite, anticancer activity

  7. Analysis and evaluation of the antimicrobial and anticancer activities of the essential oil isolated from Foeniculum vulgare from Hamedan, Iran.

    Science.gov (United States)

    Akhbari, Maryam; Kord, Reza; Jafari Nodooshan, Saeedeh; Hamedi, Sepideh

    2018-01-07

    In this study, biological properties of the essential oil isolated from seeds of Foeniculum vulgare (F. vulgare) were evaluated. GC-MS analysis revealed Trans-Anethole (80.63%), L-Fenchone (11.57%), Estragole (3.67%) and Limonene (2.68%) were the major compounds of the essential oil. Antibacterial activity of the essential oil against nine Gram-positive and Gram-negative strains was studied using disc diffusion and micro-well dilution assays. Essential oil exhibited the antibacterial activity against three Gram-negative strains of Pseudomonas aeruginosa, Escherichia coli, and Shigella dysenteriae. The preliminary study on toxicity of seed oil was performed using Brine Shrimp lethality test (BSLT). Results indicated the high toxicity effect of essential oil (LC50 = 10 μg/mL). In vitro anticancer activity of seed oil was investigated against human breast cancer (MDA-Mb) and cervical epithelioid carcinoma (Hela) cell lines by MTT assay. Results showed the seed oil behave as a very potent anticancer agent with IC50 of lower than 10 μg/mL in both cases.

  8. In Vitro Studies on Phytochemical Content, Antioxidant, Anticancer, Immunomodulatory, and Antigenotoxic Activities of Lemon, Grapefruit, and Mandarin Citrus Peels.

    Science.gov (United States)

    Diab, Kawthar Ae

    2016-01-01

    In recent years, there has been considerable research on recycling of agroindustrial waste for production of bioactive compounds. The food processing industry produces large amounts of citrus peels that may be an inexpensive source of useful agents. The present work aimed to explore the phytochemical content, antioxidant, anticancer, antiproliferation, and antigenotxic activities of lemon, grapefruit, and mandarin peels. Peels were extracted using 98% ethanol and the three crude extracts were assessed for their total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant activity using DPPH (1, 1diphenyl2picrylhydrazyl). Their cytotoxic and mitogenic proliferation activities were also studied in human leukemia HL60 cells and mouse splenocytes by CCK8 assay. In addition, genotoxic/ antigenotoxic activity was explored in mouse splenocytes using chromosomal aberrations (CAs) assay. Lemon peels had the highest of TPC followed by grapefruit and mandarin. In contrast, mandarin peels contained the highest of TFC followed by lemon and grapefruit peels. Among the extracts, lemon peel possessed the strongest antioxidant activity as indicated by the highest DPPH radical scavenging, the lowest effective concentration 50% (EC50= 42.97 ?g extract/ mL), and the highest Trolox equivalent antioxidant capacity (TEAC=0.157). Mandarin peel exhibited moderate cytotoxic activity (IC50 = 77.8 ?g/mL) against HL60 cells, whereas grapefruit and lemon peels were ineffective antileukemia. Further, citrus peels possessed immunostimulation activity via augmentation of proliferation of mouse splenocytes (Tlymphocytes). Citrus extracts exerted noncytotoxic, and antigenotoxic activities through remarkable reduction of CAs induced by cisplatin in mouse splenocytes for 24 h. The phytochemical constituents of the citrus peels may exert biological activities including anticancer, immunostimulation and antigenotoxic potential.

  9. Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

    Science.gov (United States)

    de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

    2016-01-01

    Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. PMID:27306095

  10. Inhibition of transmembrane member 16A calcium-activated chloride channels by natural flavonoids contributes to flavonoid anticancer effects.

    Science.gov (United States)

    Zhang, Xuan; Li, Honglin; Zhang, Huiran; Liu, Yani; Huo, Lifang; Jia, Zhanfeng; Xue, Yucong; Sun, Xiaorun; Zhang, Wei

    2017-07-01

    Natural flavonoids are ubiquitous in dietary plants and vegetables and have been proposed to have antiviral, antioxidant, cardiovascular protective and anticancer effects. Transmembrane member 16A (TMEM16A)-encoded Ca 2+ -activated Cl - channels play a variety of physiological roles in many organs and tissues. Overexpression of TMEM16A is also believed to be associated with cancer progression. Therefore, inhibition of TMEM16A current may be a potential target for cancer therapy. In this study, we screened a broad spectrum of flavonoids for their inhibitory activities on TMEM16A currents. A whole-cell patch technique was used to record the currents. The BrdU assay and transwell technique were used to investigate cell proliferation and migration. At a concentration of 100 μM, 10 of 20 compounds caused significant (>50%) inhibition of TMEM16A currents. The four most potent compounds - luteolin, galangin, quercetin and fisetin - had IC 50 values ranging from 4.5 to 15 μM). To examine the physiological relevance of these findings, we also studied the effects of these flavonoids on endogenous TMEM16A currents in addition to cell proliferation and migration in LA795 cancer cells. Among the flavonoids tested, we detected a highly significant correlation between TMEM16A current inhibition and cell proliferation or reduction of migration. This study demonstrates that flavonoids inhibit TMEM16A currents and suggests that flavonoids could have anticancer effects via this mechanism. © 2017 The British Pharmacological Society.

  11. In vitro Evaluation of Antimitotic, Antiproliferative, DNA fragmentation and Anticancer activity of Chloroform and Ethanol extracts of Revia hypocrateriformis

    Directory of Open Access Journals (Sweden)

    Saboo Shweta S

    2012-05-01

    Full Text Available Objective: The plant Rivea hypocrateriformis (RH has numerous therapeutic utility in folk medicine having antidiabetic, antidepressant, analgesic as well as pregnancy irruption and anticancer properties. This led us to carry out the evaluation of plant for antimitotic, antiproliferative and cytotoxicity studies. Materials and Method: The dried aerial parts of RH were successively extracted with petroleum ether, chloroform, ethanol and water. All extracts are subjected to in vitro Antimitotic and Antiproliferative assay by Allium cepa root inhibition and yeast model. The successive chloroform, SCH and ethanol extract, SEE was subjected to in vitro anticancer activity by SRB assay MCF-7, HOP-62, MOLT-4, HCT-15 and PRO cell lines. Results: The SCH and SEE shows significant antimitotic and antiproliferative activity. The mitotic index was found to be 12.14 and 14.24 mg/mL respectively, which was near to standard, Methothrexate 11.39. The IC50 value of antiproliferative assay was found to be 47.88 to 27.12 mg/mL for SCH and SEE respectively. Conclusions: Based on these results, it is concluded that RH may be the good candidate for the treatment of cancer as SCH and SEE are cytotoxic against various cell line in SRB assay.

  12. Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity.

    Science.gov (United States)

    Jayakumar, Sundarraj; Patwardhan, Raghavendra S; Pal, Debojyoti; Singh, Babita; Sharma, Deepak; Kutala, Vijay Kumar; Sandur, Santosh Kumar

    2017-12-01

    Mitocurcumin is a derivative of curcumin, which has been shown to selectively enter mitochondria. Here we describe the anti-tumor efficacy of mitocurcumin in lung cancer cells and its mechanism of action. Mitocurcumin, showed 25-50 fold higher efficacy in killing lung cancer cells as compared to curcumin as demonstrated by clonogenic assay, flow cytometry and high throughput screening assay. Treatment of lung cancer cells with mitocurcumin significantly decreased the frequency of cancer stem cells. Mitocurcumin increased the mitochondrial reactive oxygen species (ROS), decreased the mitochondrial glutathione levels and induced strand breaks in the mitochondrial DNA. As a result, we observed increased BAX to BCL-2 ratio, cytochrome C release into the cytosol, loss of mitochondrial membrane potential and increased caspase-3 activity suggesting that mitocurcumin activates the intrinsic apoptotic pathway. Docking studies using mitocurcumin revealed that it binds to the active site of the mitochondrial thioredoxin reductase (TrxR2) with high affinity. In corroboration with the above finding, mitocurcumin decreased TrxR activity in cell free as well as the cellular system. The anti-cancer activity of mitocurcumin measured in terms of apoptotic cell death and the decrease in cancer stem cell frequency was accentuated by TrxR2 overexpression. This was due to modulation of TrxR2 activity to NADPH oxidase like activity by mitocurcumin, resulting in higher ROS accumulation and cell death. Thus, our findings reveal mitocurcumin as a potent anticancer agent with better efficacy than curcumin. This study also demonstrates the role of TrxR2 and mitochondrial DNA damage in mitocurcumin mediated killing of cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Impact of Stepwise NH2-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention.

    Science.gov (United States)

    Kowol, Christian R; Miklos, Walter; Pfaff, Sarah; Hager, Sonja; Kallus, Sebastian; Pelivan, Karla; Kubanik, Mario; Enyedy, Éva A; Berger, Walter; Heffeter, Petra; Keppler, Bernhard K

    2016-07-28

    One of the most promising classes of iron chelators are α-N-heterocyclic thiosemicarbazones with Triapine as the most prominent representative. In several clinical trials Triapine showed anticancer activity against hematological diseases, however, studies on solid tumors failed due to widely unknown reasons. Some years ago, it was recognized that "terminal dimethylation" of thiosemicarbazones can lead to a more than 100-fold increased activity, probably due to interactions with cellular copper depots. To better understand the structural requirements for the switch to nanomolar cytotoxicity, we systematically synthesized all eight possible N-methylated derivatives of Triapine and investigated their potential against Triapine-sensitive as well as -resistant cell lines. While only the "completely" methylated compound exerted nanomolar activity, the data revealed that all compounds with at least one N-dimethylation were not affected by acquired Triapine resistance. In addition, these compounds were highly synergistic with copper treatment accompanied by induction of reactive oxygen species and massive necrotic cell death.

  14. A novel imidazopyridine PI3K inhibitor with anticancer activity in non-small cell lung cancer cells.

    Science.gov (United States)

    Lee, Hyunseung; Kim, Soo Jung; Jung, Kyung Hee; Son, Mi Kwon; Yan, Hong Hua; Hong, Sungwoo; Hong, Soon-Sun

    2013-08-01

    Lung cancer is the leading cause of cancer-related mortality in the world, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases. Since more than 60% of NSCLC cases express the epidermal growth factor receptor (EGFR), EGFR tyrosine kinase inhibitors are used to treat NSCLC. However, due to the acquired resistance associated with EGFR-targeted therapy, other strategies for the treatment of NSCLC are urgently needed. Therefore, we investigated the anticancer effects of a novel phosphatidylinositol 3-kinase α (PI3Kα) inhibitor, HS-173, in human NSCLC cell lines. HS-173 demonstrated anti-proliferative effects in NSCLC cells and effectively inhibited the PI3K signaling pathway in a dose‑dependent manner. In addition, it induced cell cycle arrest at G2/M phase as well as apoptosis. Taken together, our results demonstrate that HS-173 exhibits anticancer activities, including the induction of apoptosis, by blocking the PI3K/Akt/mTOR pathway in human NSCLC cell lines. We, therefore, suggest that this novel drug could potentially be used for targeted NSCLC therapy.

  15. Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid.

    Science.gov (United States)

    Barahuie, Farahnaz; Saifullah, Bullo; Dorniani, Dena; Fakurazi, Sharida; Karthivashan, Govindarajan; Hussein, Mohd Zobir; Elfghi, Fawzi M

    2017-05-01

    We have synthesized graphene oxide using improved Hummer's method in order to explore the potential use of the resulting graphene oxide as a nanocarrier for an active anticancer agent, chlorogenic acid (CA). The synthesized graphene oxide and chlorogenic acid-graphene oxide nanocomposite (CAGO) were characterized using Fourier transform infrared (FTIR) spectroscopy, thermogravimetry and differential thermogravimetry analysis, Raman spectroscopy, powder X-ray diffraction (PXRD), UV-vis spectroscopy and high resolution transmission electron microscopy (HRTEM) techniques. The successful conjugation of chlorogenic acid onto graphene oxide through hydrogen bonding and π-π interaction was confirmed by Raman spectroscopy, FTIR analysis and X-ray diffraction patterns. The loading of CA in the nanohybrid was estimated to be around 13.1% by UV-vis spectroscopy. The release profiles showed favourable, sustained and pH-dependent release of CA from CAGO nanocomposite and conformed well to the pseudo-second order kinetic model. Furthermore, the designed anticancer nanohybrid was thermally more stable than its counterpart. The in vitro cytotoxicity results revealed insignificant toxicity effect towards normal cell line, with a viability of >80% even at higher concentration of 50μg/mL. Contrarily, CAGO nanocomposite revealed enhanced toxic effect towards evaluated cancer cell lines (HepG2 human liver hepatocellular carcinoma cell line, A549 human lung adenocarcinoma epithelial cell line, and HeLa human cervical cancer cell line) compared to its free form. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. One-dimensional poly(L-lysine)-block-poly(L-threonine) assemblies exhibit potent anticancer activity by enhancing membranolysis.

    Science.gov (United States)

    Chen, Yu-Fon; Shiau, Ai-Li; Chang, Sue-Joan; Fan, Nai-Shin; Wang, Chung-Teng; Wu, Chao-Liang; Jan, Jeng-Shiung

    2017-06-01

    Herein, we report the oncolytic activity of cationic, one-dimensional (1D) fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via the mitochondria-lytic effect. The concept is analogous to that of 1D drug carriers that exhibit enhanced cell penetration. In comparison to free PLL chains, PLL-b-PLT fibril assemblies exhibit selective cytotoxicity toward cancer cells, low hemolysis activity, enhanced membranolytic activity, and a different apoptosis pathway, which may be due to differences in the peptide-membrane interactions. Antitumor studies using a metastatic LL2 lung carcinoma model indicate that the fibril assemblies significantly inhibited tumor growth, improved survival in tumor-bearing mice and suppressed lung metastasis without obvious body weight loss. An additive efficacy was also observed for treatment with both PLL-b-PLT and cisplatin. These results support the feasibility of using 1D fibril assemblies as potential apoptotic anticancer therapeutics. We report that cationic, one-dimensional (1D) fibril assemblies formed by coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides exhibited potent anticancer activity by enhancing membranolysis. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via mitochondria-lytic effect. Moreover, the fibril assemblies exhibited low hemolytic activity and selective cytotoxicity toward cancer cell, which is advantageous as compared to PLL and most antimicrobial/anticancerous peptides. This study provides a new concept of using cationic, 1D fibril assemblies for cancer therapy

  17. Evaluation of anticancer activity of Cordia dichotoma leaves against a human prostate carcinoma cell line, PC3.

    Science.gov (United States)

    Rahman, Md Azizur; Sahabjada; Akhtar, Juber

    2017-07-01

    Mechanisms of antioxidant and apoptosis induction may be involved in the management of cancer by medicinal plants. Aim of the study was designed to evaluate anticancer activity of the methanolic extract of Cordia dichotoma leaves (MECD) against a human prostate carcinoma cell line, PC3. Flavonoid content was determined by colorimetric principle and antioxidant activity by various in vitro assays. MTT, DCFH-DA and DAPI staining assays were performed for the evaluation of cytotoxicity, analysis of induction of apoptosis and intracellular reactive oxygen species (ROS) activity level by MECD against human prostate carcinoma cell line, PC3. Flavonoid content was found to be 160 mg QE/g extract. IC 50 values for MECD treatment in various assays based on scavenging of 2,2-diphenyl-1-picrylhydrazyl, 2,2-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid), nitric oxide, peroxy radical, superoxide anion, hydroxy radical were found to be 315.5, 38, 476, 523, 197, 82 μg/ml respectively. MECD exposure to PC3 cells significantly increased the cell death (p < 0.001, IC 50  = 74.5 μg/ml), nuclear condensation, apoptosis (p < 0.001) and induced production of ROS (p < 0.001) initiating apoptotic cascade in a dose dependent manner. This study confirms that MECD possesses antioxidant property and can prevent carcinogenesis by reducing oxidative stress. MECD possesses anticancer activity and lead to PC3 cell death via induction of apoptosis mediated through excessive ROS generation. Flavonoids in MECD may be responsible for these activities due to dual antioxidant and pro-oxidant properties.

  18. Anticancer properties of brassinosteroids

    Czech Academy of Sciences Publication Activity Database

    Swaczynová, Jana; Malíková, J.; Hoffmannová, L.; Kohout, Ladislav; Strnad, Miroslav

    2007-01-01

    Roč. 72, č. 11 (2007), - ISSN 0032-0943. [Annual Congress on Medicinal Plant Research /54./. 29.08.2006-02.09.2006, Helsinki] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50380511 Keywords : brassinosteroids * anticancer activity * proliferation * apoptosis Subject RIV: CC - Organic Chemistry

  19. Antioxidant and anticancer activities of freshwater green algae, Cladophora glomerata and Microspora floccosa, from Nan River in northern Thailand

    Directory of Open Access Journals (Sweden)

    Warawut Chulalaksananukul

    2013-05-01

    Full Text Available Organic solvent and hot water extracts of freshwater macroalgae, Cladophora glomerata and Microspora floccosa, harvested from Nan River in northern Thailand were screened for antioxidant and anticancer activities using DPPH free radical scavenging assay and inhibition of proliferation of the KB human oral cancer cell lines respectively. The ethyl acetate extract of C. glomerata showed the highest total phenol content (18.1±2.3 mg GAE/g, radical scavenging activity (49.8±2.7% DPPH scavenging at 100 g/ml and in vitro growth inhibition (IC50=1420.0±66 g/g of the KB cell lines. These results indicate that C. glomerata could be a source of valuable bioactive materials.

  20. Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents.

    Science.gov (United States)

    Penthala, Narsimha Reddy; Zong, Hongliang; Ketkar, Amit; Madadi, Nikhil Reddy; Janganati, Venumadav; Eoff, Robert L; Guzman, Monica L; Crooks, Peter A

    2015-03-06

    A series of heterocyclic combretastatin analogues have been synthesized and evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compounds were two 3,4,5-trimethoxy phenyl analogues containing either an (Z)-indol-2-yl (8) or (Z)-benzo[b]furan-2-yl (12) moiety; these compounds exhibited GI50 values of Compounds 8, and 12 and two previously reported compounds in the same structural class, i.e. 29 and 31, also showed potent anti-leukemic activity against leukemia MV4-11 cell lines with LD50 values = 44 nM, 47 nM, 18 nM, and 180 nM, respectively. From the NCI anti-cancer screening results and the data from the in vitro toxicity screening on cultured AML cells, seven compounds: 8, 12, 21, 23, 25, 29 and 31 were screened for their in vitro inhibitory activity on tubulin polymerization in MV4-11 AML cells; at 50 nM, 8 and 29 inhibited polymerization of tubulin by >50%. The binding modes of the three most active compounds (8, 12 and 29) to tubulin were also investigated utilizing molecular docking studies. All three molecules were observed to bind in the same hydrophobic pocket at the interface of α- and β-tubulin that is occupied by colchicine, and were stabilized by van der Waals' interactions with surrounding tubulin residues. The results from the tubulin polymerization and molecular docking studies indicate that compounds 8 and 29 are the most potent anti-leukemic compounds in this structural class, and are considered lead compounds for further development as anti-leukemic drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. In vitro study of the antibacterial and anticancer activities of silver nanoparticles synthesized from Penicillium brevicompactum (MTCC-1999

    Directory of Open Access Journals (Sweden)

    Shahnaz Majeed

    2016-07-01

    Full Text Available Among the most promising nanomaterials, metallic nanoparticles with antibacterial and antitumor properties are expected to open new avenues to fight and prevent various tumours and infectious diseases. The study of bactericidal nanomaterial is particularly timely considering the recent increase in new resistant strains of bacteria to the most potent antibiotics and the potential role of bactericidal nanomaterial as anticancer agents. This has promoted the research of the well-known activity of silver ions and silver-based compounds, including silver nanoparticles. The present work is the study of silver nanoparticles synthesized from Penicillium brevicompactum (MTCC-1999. The colour of the cell filtrate changes to dark brown upon addition of 1 mM AgNO3, suggesting the formation of silver nanoparticles. These silver nanoparticles (AgNPs were characterized and analyzed by UV–vis spectrophotometric analysis, which showed a peak of absorbance at 420 nm. Fourier transform infrared (FTIR analysis showed amines and amides that are responsible for the stabilization of AgNPs. To determine the particle size, atomic force microscopy (AFM analysis was used, which showed that the nanoparticles are spherical and are 30–50 nm in size. High-resolution transmission electron microscopy (HRTEM showed that AgNPs were well dispersed, spherical, and well within the range of 40–50 nm. These nanoparticles displayed good antibacterial activity and also increased the antibiotic activity of gatifloxacin, tetracycline, and vancomycin. These nanoparticles were further studied for their anticancer activity and showed high toxicity towards the MCF-7 breast cancer cell line.

  2. Synthesis, DNA binding ability and anticancer activity of 2-heteroaryl substituted benzimidazoles linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.

    Science.gov (United States)

    Kamal, Ahmed; Pogula, Praveen Kumar; Khan, Mohammed Naseer Ahmed; Seshadri, Bobburi Naga; Sreekanth, Kokkonda

    2013-08-01

    As a continuation of our efforts to develop the benzimidazole-PBD conjugates as potential anticancer agents, a series of heteroaryl substituted benzimidazole linked PBD conjugates has been synthesized and evaluated for their anticancer potential in 60 human cancer cell lines. Most of the compounds exhibited promising anticancer activity and interestingly, compounds 4c and 4d displayed significant activity in most of the cell lines tested. Whereas, compound 4e showed selectivity in renal cancer cells with GI50 values of <10 and 70 nM against RXF 393 and UO-31 cell lines, respectively. Further, these compounds also showed significant DNA-binding affinity by thermal denaturation study using duplex form of calf thymus (CT) DNA.

  3. Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II acceptors

    Directory of Open Access Journals (Sweden)

    Kim I

    2015-08-01

    Full Text Available Inhye Kim,1,* Young Ho Song,2,* Nem Singh,2 Yong Joon Jeong,3 Jung Eun Kwon,3 Hyunuk Kim,4 Young Mi Cho,3 Se Chan Kang,3 Ki-Whan Chi2 1Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, 2Department of Chemistry, University of Ulsan, Ulsan, 3Department of Life Science, Gachon University, Seongnam, 4Energy Materials Lab, Korea Institute of Energy Research, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II molecular bowls. [2+2] Coordination-driven self-assembly of 3,6-bis(pyridin-3-ylethynylphenanthrene (bpep (1 and one of the three dinuclear arene ruthenium clips, [(ƞ6-p-iPrC6H4Me2Ru2-(OO\\OO][OTf]2 (OO\\OO =2,5-dioxido-1,4-benzoquinonato, OTf = triflate (2, 5,8-dioxido-1,4-naphthoquinonato (3, or 6,11-dioxido-5,12-naphthacenediona (4, resulted in three molecular bowls 5–7 of general formula [{(ƞ6-p-iPrC6H4Me2Ru2-(OO\\OO}2(bpep2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90% and were fully characterized using multinuclear nuclear magnetic resonance (NMR, electrospray ionization–mass spectrometry (ESI-MS, and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5–7 were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation

  4. Green synthesis of selenium nanoparticles using Acinetobacter sp. SW30: optimization, characterization and its anticancer activity in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Wadhwani SA

    2017-09-01

    Full Text Available Sweety A Wadhwani,1 Mahadeo Gorain,2 Pinaki Banerjee,2 Utkarsha U Shedbalkar,3 Richa Singh,1 Gopal C Kundu,2 Balu A Chopade1,4 1Department of Microbiology, Savitribai Phule Pune University, 2Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Center for Cell Science, Savitribai Phule Pune University Campus, Pune, 3Department of Biochemistry, The Institute of Science, Mumbai, 4Dr Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India Abstract: The aim of this study was to synthesize selenium nanoparticles (SeNPs using cell suspension and total cell protein of Acinetobacter sp. SW30 and optimize its synthesis by studying the influence of physiological and physicochemical parameters. Also, we aimed to compare its anticancer activity with that of chemically synthesized SeNPs in breast cancer cells. Cell suspension of Acinetobacter sp. SW30 was exposed to various physiological and physicochemical conditions in the presence of sodium selenite to study their effects on the synthesis and morphology of SeNPs. Breast cancer cells (4T1, MCF-7 and noncancer cells (NIH/3T3, HEK293 were exposed to different concentrations of SeNPs. The 18 h grown culture with 2.7×109 cfu/mL could synthesize amorphous nanospheres of size 78 nm at 1.5 mM and crystalline nanorods at above 2.0 mM Na2SeO3 concentration. Polygonal-shaped SeNPs of average size 79 nm were obtained in the supernatant of 4 mg/mL of total cell protein of Acinetobacter sp. SW30. Chemical SeNPs showed more anticancer activity than SeNPs synthesized by Acinetobacter sp. SW30 (BSeNPs, but they were found to be toxic to noncancer cells also. However, BSeNPs were selective against breast cancer cells than chemical ones. Results suggest that BSeNPs are a good choice of selection as anticancer agents. Keywords: comparison, selective, 4T1, MCF7

  5. Structural characterization and evaluation of antioxidant, anticancer and hypoglycemic activity of radiation degraded oat (Avena sativa) β- glucan

    Science.gov (United States)

    Hussain, Peerzada R.; Rather, Sarver A.; Suradkar, Prashant P.

    2018-03-01

    Oat β-D-glucan after extraction was degraded at doses of 3, 6, 9, 12 and 15 kGy. The average molecular weight decreased to 45 kDa at dose of 15 kGy from an initial value of 200 kDa in native sample. XRD analysis revealed no significant change in diffraction pattern of irradiated samples when compared with control, except a decrease in intensity of x-ray diffraction. The results of the antioxidant activity revealed decrease in EC50 values and corresponding increase in antioxidant activity of radiation degraded oat β-D-glucan. Results of the anticancer studies indicated that cytotoxicity of gamma irradiated oat β-D-glucan in cancer cell lines was highest against colo-205 and MCF7 cancer cells compared to T47D cell and no cytotoxicity was observed in normal cell lines at all concentrations used. Evaluation of hypoglycemic activity showed highest inhibition in α-glucosidase activity compared to α-amylase activity due to gamma irradiation of oat β-D-glucan. Comparison of the EC50 values of known standards and gamma irradiated oat beta-glucan samples indicates that radiation treatment significantly modified the biological activity of the beta-glucan samples. Therefore, it is suggested that gamma irradiation can be used for producing low molecular weight oat β-D-glucan; which can help in modifying the biological activities.

  6. Ag@Ag_8W_4O_1_6 nanoroasted rice beads with photocatalytic, antibacterial and anticancer activity

    International Nuclear Information System (INIS)

    Selvamani, Muthamizh; Krishnamoorthy, Giribabu; Ramadoss, Manigandan; Sivakumar, Praveen Kumar; Settu, Munusamy; Ranganathan, Suresh; Vengidusamy, Narayanan

    2016-01-01

    Increasing resistance of pathogens and cancer cell line towards antibiotics and anticancer agents has caused serious health problems in the past decades. Due to these problems in recent years, researchers have tried to combine nanotechnology with material science to have intrinsic antimicrobial and anticancer activity. The metals and metal oxides were investigated with respect to their antimicrobial and anticancer effects towards bacteria and cancer cell line. In the present work metal@metal tungstate (Ag@Ag_8W_4O_1_6 nanoroasted rice beads) is investigated for antibacterial activity against Escherichia coli and Staphylococcus aureus using Mueller-Hinton broth and the anticancer activity against B16F10 cell line was studied. Silver decorated silver tungstate (Ag@Ag_8W_4O_1_6) was synthesized by the microwave irradiation method using Cetyl Trimethyl Ammonium Bromide (CTAB). Ag@Ag_8W_4O_1_6 was characterized by using various spectroscopic techniques. The phase and crystalline nature were analyzed by using XRD. The morphological analysis was carried out using Field Emission Scanning Electron Microscopy (FE-SEM), and High Resolution Transmission Electron Microscopy (HR-TEM). Further, Fourier Transform Infrared Spectroscopy (FT-IR) and Raman spectral analysis were carried out in order to ascertain the presence of functional groups in Ag@Ag_8W_4O_1_6. The optical property was investigated using Diffuse Reflectance Ultraviolet–Visible Spectroscopy (DRS-UV–Vis) and the band gap was found to be 3.08 eV. Surface area of the synthesized Ag@Ag_8W_4O_1_6 wasanalyzed by BET analysis and Ag@Ag_8W_4O_1_6 was utilized for the degradation of organic dyes methylene blue and rhodamine B. The morphology of the Ag@Ag_8W_4O_1_6 resembles roasted rice beads with breath and length in nm range. The oxidation state of tungsten (W) and silver (Ag) was investigated using X-ray photoelectron spectroscopy (XPS). - Highlights: • Synthesis of Ag@Ag_8W_4O_1_6 nanoroasted rice beads using

  7. Anticancer effect of (S)-crizotinib on osteosarcoma cells by targeting MTH1 and activating reactive oxygen species.

    Science.gov (United States)

    Qing, Xiangcheng; Shao, Zengwu; Lv, Xiao; Pu, Feifei; Gao, Feng; Liu, Lei; Shi, Deyao

    2018-04-01

    MTH1 has become a new rising star in the field of 'cancer phenotypic lethality' and can be targeted in many kinds of tumors. This study aimed to explore the anticancer effect of MTH1-targeted drug (S)-crizotinib on osteosarcoma (OS) cells. We detected MTH1 expression in OS tissues and cells using immunohistochemistry and western blot. The effects of MTH1 on OS cell viability were explored using the siRNA technique and CCK8. The anticancer effects of the MTH1-targeted drug (S)-crizotinib on OS cells were explored by in-vitro assays. The intracellular 8-oxo-dGTP level and oxygen reactive species (ROS) of OS cells were detected by Cy3-conjugated avidin staining and dichlorofluorescein diacetate staining, respectively. The expression of MTH1 was significantly higher in OS tissues and cell lines than that in the corresponding adjacent tissues and osteoblastic cell line. The proliferation of OS cells was significantly inhibited through knockdown of MTH1 by siRNA technology. (S)-Crizotinib could inhibit the proliferation of OS cells with an increase in the apoptosis levels and causing G0/G1 arrest by targeting MTH1 and activating ROS. In addition, (S)-crizotinib could inhibit the migration of OS cells. (S)-Crizotinib could suppress the proliferation and migration, cause G0/G1 arrest, and increase the apoptosis level of OS cells by targeting MTH1 and activating ROS. This study will provide a promising therapeutic target and the theoretical basis for the clinical application of (S)-crizotinib in OS.

  8. Anticancer activity of biologically synthesized silver and gold nanoparticles on mouse myoblast cancer cells and their toxicity against embryonic zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Ramachandran, Rajan [Centre for Advanced Studies in Botany, School of Life Sciences, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu (India); Krishnaraj, Chandran [Department of Food Science & Technology, College of Agriculture & Life Sciences, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); M/s. Eureka Forbes Ltd, R & D Centre, Kudlu, Bangalore (India); Sivakumar, Allur Subramaniyan [Department of Animal Biotechnology, Chonbuk National University, Jeonju 54896 (Korea, Republic of); Prasannakumar, Palaniappan [Advanced Biomedical Imaging Center, Department of Electronic Engineering, Chonbuk National University, Jeonju 54896 (Korea, Republic of); Abhay Kumar, V.K. [M/s. Eureka Forbes Ltd, R & D Centre, Kudlu, Bangalore (India); Shim, Kwan Seob [Department of Animal Biotechnology, Chonbuk National University, Jeonju 54896 (Korea, Republic of); Song, Chul-Gyu [Advanced Biomedical Imaging Center, Department of Electronic Engineering, Chonbuk National University, Jeonju 54896 (Korea, Republic of); Yun, Soon-Il, E-mail: siyun@jbnu.ac.kr [Department of Food Science & Technology, College of Agriculture & Life Sciences, Chonbuk National University, Jeonju 561-756 (Korea, Republic of)

    2017-04-01

    The aim of this study was to evaluate the anticancer activity of bioinspired silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) against mouse myoblast cancer cells (C{sub 2}C{sub 12}). Both AgNPs and AuNPs were biologically synthesized using Spinacia oleracea Linn., aqueous leaves extract. UV–Vis. spectrophotometer, high resolution-transmission electron microscopy (HR-TEM), field emission-scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD) studies supported the successful synthesis of AgNPs and AuNPs. Both these NPs have shown cytotoxicity against C{sub 2}C{sub 12} cells even at very low concentration (5 μg/mL). Acridine orange/Ethidium bromide (AO/EB) dual staining confirmed the apoptotic morphological features. The levels of caspase enzymes (caspase-3 and caspase-7) were significantly up-regulated in NPs treated myoblast cells than the plant extract. Furthermore, in zebrafish embryo toxicity study, AgNPs showed 100% mortality at 3 μg/mL concentration while AuNPs exhibited the same at much higher concentration (300 mg/mL). Taken together, these results provide a preliminary guidance for the development of biomaterials based drugs to fight against the fatal diseases for example cancer. - Highlights: • Anticancer activity was done for the first time against mouse myoblast cells. • AgNPs showed 100% growth inhibition against C{sub 2}C{sub 12} cells at 20 μg/mL concentration. • AO/EB dual staining and caspase assays confirmed the apoptotic features. • Nanoparticles treated embryos showed yolk sac edema and tail malformation. • AgNPs were found to be more toxic to embryonic zebrafishes than the AuNPs.

  9. Anticancer activity of biologically synthesized silver and gold nanoparticles on mouse myoblast cancer cells and their toxicity against embryonic zebrafish

    International Nuclear Information System (INIS)

    Ramachandran, Rajan; Krishnaraj, Chandran; Sivakumar, Allur Subramaniyan; Prasannakumar, Palaniappan; Abhay Kumar, V.K.; Shim, Kwan Seob; Song, Chul-Gyu; Yun, Soon-Il

    2017-01-01

    The aim of this study was to evaluate the anticancer activity of bioinspired silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) against mouse myoblast cancer cells (C 2 C 12 ). Both AgNPs and AuNPs were biologically synthesized using Spinacia oleracea Linn., aqueous leaves extract. UV–Vis. spectrophotometer, high resolution-transmission electron microscopy (HR-TEM), field emission-scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD) studies supported the successful synthesis of AgNPs and AuNPs. Both these NPs have shown cytotoxicity against C 2 C 12 cells even at very low concentration (5 μg/mL). Acridine orange/Ethidium bromide (AO/EB) dual staining confirmed the apoptotic morphological features. The levels of caspase enzymes (caspase-3 and caspase-7) were significantly up-regulated in NPs treated myoblast cells than the plant extract. Furthermore, in zebrafish embryo toxicity study, AgNPs showed 100% mortality at 3 μg/mL concentration while AuNPs exhibited the same at much higher concentration (300 mg/mL). Taken together, these results provide a preliminary guidance for the development of biomaterials based drugs to fight against the fatal diseases for example cancer. - Highlights: • Anticancer activity was done for the first time against mouse myoblast cells. • AgNPs showed 100% growth inhibition against C 2 C 12 cells at 20 μg/mL concentration. • AO/EB dual staining and caspase assays confirmed the apoptotic features. • Nanoparticles treated embryos showed yolk sac edema and tail malformation. • AgNPs were found to be more toxic to embryonic zebrafishes than the AuNPs.

  10. The Role of Endophytic Fungi in the Anticancer Activity of Morinda citrifolia Linn. (Noni

    Directory of Open Access Journals (Sweden)

    Yougen Wu

    2015-01-01

    Full Text Available We hypothesize that the fungal endophytes of noni may possibly play a role in its overall pharmacological repertoire, especially since the perceived efficacy of the fruit in ethnomedicinal use is associated with the fermented juice. The foremost goal of this study is to explore the role of endophyte-derived secondary metabolites in the purported anticancer properties of noni. To that end, culturable endophytic fungi resident within the healthy leaves and fruit of the plant were isolated and identified by molecular sequence analysis of the 5.8S gene and internal transcribed spacers (ITS. Purified organisms were subjected to in vitro fermentation in malt extract broth for 8 weeks under anaerobic conditions at room temperature (25°C, in order to simulate the conditions under which traditional fermented noni juice is prepared. The cytotoxic potential of organic extracts derived from the fermented broths of individual endophytes was then tested against three major cancers that afflict humans. Twelve distinct endophytic fungal species were obtained from the leaves and 3 from the fruit. Three of the leaf endophytes inhibited the growth of human carcinoma cell lines LU-1 (lung, PC-3 (prostate, and MCF-7 (breast with IC50 values of ≤10 μg/mL.

  11. A galactomannan polysaccharide from Punica granatum imparts in vitro and in vivo anticancer activity.

    Science.gov (United States)

    Joseph, Manu M; Aravind, S R; George, Suraj K; Varghese, Sheeja; Sreelekha, T T

    2013-11-06

    Galactomannan polysaccharide (PSP001) was isolated from the fruit rind of Punica granatum and was previously reported to have excellent antioxidant and immunomodulatory properties. The cytotoxicity of PSP001 was evaluated in the human cancer cell lines A375, HCT116, and HepG2 as well as the murine cancer cell lines DLA and EAC over a wide range of concentrations. PSP001 exhibited significant cytotoxicity against cancer cells through the induction of apoptosis with no in vivo toxicity up to a concentration of 2000 mg/kg body weight when assessed in BALB/c mice. The antitumor efficacy of PSP001 was tested in DLA and EAC murine ascites and EAC solid tumor mouse models. PSP001 alone and in combination with doxorubicin produced a significant reduction in the tumor burden and increased life span in both models compared to the controls. The results suggest that PSP001 has the potential to be developed as an anticancer agent either alone or as an adjuvant to chemotherapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Chan-on W

    2015-04-01

    Full Text Available Waraporn Chan-on,1 Nguyen Thi Bich Huyen,2 Napat Songtawee,3 Wilasinee Suwanjang,1 Supaluk Prachayasittikul,3 Virapong Prachayasittikul2 1Center for Research and Innovation, 2Department of Clinical Microbiology and Applied Technology, 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand Purpose: Fork head box M1 (FoxM1 is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA. A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ and nitroxoline (NQ, represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells.Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl-5-(3-carboxymethoxyphenyl-(4-sulfophenyl-2H-tetrazolium (MTS assay. Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction.Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment

  13. In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum).

    Science.gov (United States)

    Majdalawieh, Amin F; Carr, Ronald I

    2010-04-01

    Although the immunomodulatory effects of many herbs have been extensively studied, research related to possible immunomodulatory effects of various spices is relatively scarce. Here, the potential immunomodulatory effects of black pepper and cardamom are investigated. Our data show that black pepper and cardamom aqueous extracts significantly enhance splenocyte proliferation in a dose-dependent, synergistic fashion. Enzyme-linked immunosorbent assay experiments reveal that black pepper and cardamom significantly enhance and suppress, respectively, T helper (Th)1 cytokine release by splenocytes. Conversely, Th2 cytokine release by splenocytes is significantly suppressed and enhanced by black pepper and cardamom, respectively. Experimental evidence suggests that black pepper and cardamom extracts exert pro-inflammatory and anti-inflammatory roles, respectively. Consistently, nitric oxide production by macrophages is significantly augmented and reduced by black pepper and cardamom, respectively. Remarkably, it is evident that black pepper and cardamom extracts significantly enhance the cytotoxic activity of natural killer cells, indicating their potential anti-cancer effects. Our findings strongly suggest that black pepper and cardamom exert immunomodulatory roles and antitumor activities, and hence they manifest themselves as natural agents that can promote the maintenance of a healthy immune system. We anticipate that black pepper and cardamom constituents can be used as potential therapeutic tools to regulate inflammatory responses and prevent/attenuate carcinogenesis.

  14. Comparative studies on the constituents, antioxidant and anticancer activities of extracts from different varieties of corn silk.

    Science.gov (United States)

    Tian, Jingge; Chen, Haixia; Chen, Shuhan; Xing, Lisha; Wang, Yanwei; Wang, Jia

    2013-10-01

    The purpose of this study was to analyze the influence of varieties on the constituents, antioxidant and anticancer activities of corn silk. The contents of total phenolic and flavonoids and individual flavonoids in six corn silk varieties (Denghai6702, Delinong988, Tunyu808, Zhongdan909, Liangyu208, Jingke968) were comparatively analyzed by colourimetric methods, high performance liquid chromatography (HPLC) methods and antioxidant activities were assessed using a panel of in vitro assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity assay, the inhibitory effects on lipid peroxidation (MDA) assay and ferric reducing/antioxidant power (FRAP) assay, and the cytotoxicity against human prostatic carcinoma cells PC3 and breast carcinoma cells MDA-MB-231 and MCF7 were also evaluated. Results showed that Zhongdan909 exhibited the highest total phenolic content while Tunyu808 had the highest flavonoid content among the six species. Zhongdan909 showed the highest DPPH radical scavenging activity, the highest inhibitory effect on lipid peroxidation and the strongest cytotoxicity against breast carcinoma cells MCF7, while Tunyu808 exhibited the highest reducing power. There were good relationships between the total phenolic and flavonoid contents and antioxidant activities (r > 0.78) and the cytotoxicity against breast carcinoma cells MCF7 (r > 0.79). This study suggested that corn silk could be potentially used as a readily accessible source of natural antioxidants and formononetin was one of the main antioxidant constituents in corn silk.

  15. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Boo [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States); Lee, Seong-Ho, E-mail: slee2000@umd.edu [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  16. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    International Nuclear Information System (INIS)

    Jeong, Jin Boo; Lee, Seong-Ho

    2013-01-01

    Highlights: ► Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. ► PCA enhanced transcriptional downregulation of cyclin D1 gene. ► PCA suppressed HDAC2 expression and activity. ► These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  17. Thermodynamic Study of Water Activity of Single Strong Electrolytes

    Directory of Open Access Journals (Sweden)

    Seyed Hossein Hashemi

    2017-06-01

    Full Text Available Today, due to the natural decline of oil exploitation, the use of methods of oil recovery, has made significant progress. However, these methods are accompanied by accumulation and deposition of mineral deposits in oil field installations. In the present study, aqueous solutions, strontium sulfate, barium sulfate, manganese sulfate and nickel sulfate are studied, in terms of EUNIQUAC model and genetic algorithms. Based on the findings of this article, as temperature increases, in order to increase the solubility of the system, the ionic strength decreases; but with increasing pressure, the solubility of barium sulfate increases. Meanwhile, in this article, to evaluate water activity, aqueous solutions of manganese sulfate and nickel sulfate is studied.

  18. Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid

    Energy Technology Data Exchange (ETDEWEB)

    Barahuie, Farahnaz [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Zabol University of Medical Sciences, Zabol (Iran, Islamic Republic of); Saifullah, Bullo [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Dorniani, Dena [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Chemistry Department, University of Sheffield, Dainton Building, Brook Hill, Sheffield S3 7HF (United Kingdom); Fakurazi, Sharida [Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Karthivashan, Govindarajan [Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Hussein, Mohd Zobir, E-mail: mzobir@upm.edu.my [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Elfghi, Fawzi M. [Department of Chemical and Petrochemical Engineering, The College of Engineering & Architecture, Initial Campus, Birkat Al Mouz Nizwa (Oman)

    2017-05-01

    We have synthesized graphene oxide using improved Hummer's method in order to explore the potential use of the resulting graphene oxide as a nanocarrier for an active anticancer agent, chlorogenic acid (CA). The synthesized graphene oxide and chlorogenic acid-graphene oxide nanocomposite (CAGO) were characterized using Fourier transform infrared (FTIR) spectroscopy, thermogravimetry and differential thermogravimetry analysis, Raman spectroscopy, powder X-ray diffraction (PXRD), UV–vis spectroscopy and high resolution transmission electron microscopy (HRTEM) techniques. The successful conjugation of chlorogenic acid onto graphene oxide through hydrogen bonding and π–π interaction was confirmed by Raman spectroscopy, FTIR analysis and X-ray diffraction patterns. The loading of CA in the nanohybrid was estimated to be around 13.1% by UV–vis spectroscopy. The release profiles showed favourable, sustained and pH-dependent release of CA from CAGO nanocomposite and conformed well to the pseudo-second order kinetic model. Furthermore, the designed anticancer nanohybrid was thermally more stable than its counterpart. The in vitro cytotoxicity results revealed insignificant toxicity effect towards normal cell line, with a viability of > 80% even at higher concentration of 50 μg/mL. Contrarily, CAGO nanocomposite revealed enhanced toxic effect towards evaluated cancer cell lines (HepG2 human liver hepatocellular carcinoma cell line, A549 human lung adenocarcinoma epithelial cell line, and HeLa human cervical cancer cell line) compared to its free form. - Highlights: • Graphene oxide is synthesized using improved Hummer's method • The suppression of cancer cell growth was higher for chlorogenic acid/graphene oxide nanocomposite than for pure chlorogenic acid • Chlorogenic acid/graphene oxide nanocomposite has the potential to be used as a sustained release formulation.

  19. Lycopene loaded whey protein isolate nanoparticles: An innovative endeavor for enhanced bioavailability of lycopene and anti-cancer activity.

    Science.gov (United States)

    Jain, Ashay; Sharma, Gajanand; Ghoshal, Gargi; Kesharwani, Prashant; Singh, Bhupinder; Shivhare, U S; Katare, O P

    2018-04-28

    The work entails a novel strategy of formulating the lycopene loaded whey protein isolate nanoparticles (LYC-WPI-NPs) solely using the rational blend of biomacromolecule without using equipment-intensive techniques. The LYC-WPI-NPs were fabricated as a substantial drug delivery platform, with maximum entrapment, spatial and controlled release manners, exceptional plasma concentration, and perspective for discrepancy delivery of therapeutics. Prepared nano-formulations were measured in ultra-fine size (100-350 nm) with sphere-shaped. The percent lycopene entrapment of prepared LYC-WPI-NPs was estimated in the range to 50 and 65%. In vitro percent cumulative release study demonstrated deaden and extended release i.e. approximately 75% following 16 th h. The in vitro percent cell survival (cytotoxicity study) of prepared nanoparticles was evaluated against MCF-7 breast cancer cells by MTT based colorimetric assay. Sub-cellular localization of lycopene when delivered by LYC-WPI-NPs was assessed by HPLC (high performance liquid chromatography). The WPI-NPs enhance the oral bioavailability of lycopene by controlling its release from nano-formulation and facilitating its absorption through lymphatic pathways. Prophylactic anticancer efficacy of LYC-WPI-NPs was evaluated thereafter on experimentally induced breast cancer animal model. Conclusively, it may quite reasonable that lycopene loaded protein nanoparticles are competent to improve the biopharmaceutical attributes of lycopene and demonstrated prophylactic anticancer activity, decrease tumor proliferation and increase the survival rate of treated animals, thus signifying their feasible usefulness in cancer therapeutic and intervention. Copyright © 2018. Published by Elsevier B.V.

  20. Electrochemical and DFT study of an anticancer and active anthelmintic drug at carbon nanostructured modified electrode.

    Science.gov (United States)

    Ghalkhani, Masoumeh; Beheshtian, Javad; Salehi, Maryam

    2016-12-01

    The electrochemical response of mebendazole (Meb), an anticancer and effective anthelmintic drug, was investigated using two different carbon nanostructured modified glassy carbon electrodes (GCE). Although, compared to unmodified GCE, both prepared modified electrodes improved the voltammetric response of Meb, the carbon nanotubes (CNTs) modified GCE showed higher sensitivity and stability. Therefore, the CNTs-GCE was chosen as a promising candidate for the further studies. At first, the electrochemical behavior of Meb was studied by cyclic voltammetry and differential pulse and square wave voltammetry. A one step reversible, pH-dependent and adsorption-controlled process was revealed for electro-oxidation of Meb. A possible mechanism for the electrochemical oxidation of Meb was proposed. In addition, electronic structure, adsorption energy, band gap, type of interaction and stable configuration of Meb on the surface of functionalized carbon nanotubes were studied by using density functional theory (DFT). Obtained results revealed that Meb is weakly physisorbed on the CNTs and that the electronic properties of the CNTs are not significantly changed. Notably, CNTs could be considered as a suitable modifier for preparation of the modified electrode for Meb analysis. Then, the experimental parameters affecting the electrochemical response of Meb were optimized. Under optimal conditions, high sensitivity (b(Meb)=dIp,a(Meb)/d[Meb]=19.65μAμM(-1)), a low detection limit (LOD (Meb)=19nM) and a wide linear dynamic range (0.06-3μM) was resulted for the voltammetric quantification of Meb. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Electrochemical and DFT study of an anticancer and active anthelmintic drug at carbon nanostructured modified electrode

    International Nuclear Information System (INIS)

    Ghalkhani, Masoumeh; Beheshtian, Javad; Salehi, Maryam

    2016-01-01

    The electrochemical response of mebendazole (Meb), an anticancer and effective anthelmintic drug, was investigated using two different carbon nanostructured modified glassy carbon electrodes (GCE). Although, compared to unmodified GCE, both prepared modified electrodes improved the voltammetric response of Meb, the carbon nanotubes (CNTs) modified GCE showed higher sensitivity and stability. Therefore, the CNTs-GCE was chosen as a promising candidate for the further studies. At first, the electrochemical behavior of Meb was studied by cyclic voltammetry and differential pulse and square wave voltammetry. A one step reversible, pH-dependent and adsorption-controlled process was revealed for electro-oxidation of Meb. A possible mechanism for the electrochemical oxidation of Meb was proposed. In addition, electronic structure, adsorption energy, band gap, type of interaction and stable configuration of Meb on the surface of functionalized carbon nanotubes were studied by using density functional theory (DFT). Obtained results revealed that Meb is weakly physisorbed on the CNTs and that the electronic properties of the CNTs are not significantly changed. Notably, CNTs could be considered as a suitable modifier for preparation of the modified electrode for Meb analysis. Then, the experimental parameters affecting the electrochemical response of Meb were optimized. Under optimal conditions, high sensitivity (b(Meb) = dI p,a (Meb) / d[Meb] = 19.65 μA μM −1 ), a low detection limit (LOD (Meb) = 19 nM) and a wide linear dynamic range (0.06–3 μM) was resulted for the voltammetric quantification of Meb. - Highlights: • Electrochemical oxidation mechanism of Meb was investigated. • A carbon nanostructure modified electrode was developed for the determination of Meb. • The modified electrode surface was characterized by SEM and impedance studies. • This study provides an effective chemically modified electrode with satisfactory repeatability and reproducibility

  2. Anticancer Activity of a Hexapeptide from Skate (Raja porosa Cartilage Protein Hydrolysate in HeLa Cells

    Directory of Open Access Journals (Sweden)

    Xin Pan

    2016-08-01

    Full Text Available In this study, the hexapeptide Phe-Ile-Met-Gly-Pro-Tyr (FIMGPY, which has a molecular weight of 726.9 Da, was separated from skate (Raja porosa cartilage protein hydrolysate using ultrafiltration and chromatographic methods, and its anticancer activity was evaluated in HeLa cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT assay indicated that FIMGPY exhibited high, dose-dependent anti-proliferation activities in HeLa cells with an IC50 of 4.81 mg/mL. Acridine orange/ethidium bromide (AO/EB fluorescence staining and flow cytometry methods confirmed that FIMGPY could inhibit HeLa cell proliferation by inducing apoptosis. Western blot assay revealed that the Bax/Bcl-2 ratio and relative intensity of caspase-3 in HeLa cells treated with 7-mg/mL FIMGPY were 2.63 and 1.83, respectively, significantly higher than those of the blank control (p < 0.01. Thus, FIMGPY could induce apoptosis by upregulating the Bax/Bcl-2 ratio and caspase-3 activation. Using a DNA ladder method further confirmed that the anti-proliferation activity of FIMGPY was attributable to its role in inducing apoptosis. These results suggest that FIMGPY from skate cartilage protein hydrolysate may have applications as functional foods and nutraceuticals for the treatment and prevention of cancer.

  3. Anticancer and anti-inflammatory activities of girinimbine isolated from Murraya koenigii

    Directory of Open Access Journals (Sweden)

    Iman V

    2016-12-01

    evidenced in vivo in zebrafish embryos, with results demonstrating significant distribution of apoptotic cells in embryos after a 24-hour treatment period. Meanwhile, anti-inflammatory action was evidenced by the significant dose-dependent girinimbine inhibition of nitric oxide production in lipopolysaccharide/interferon-gamma-induced cells along with significant inhibition of nuclear factor-kappa B translocation from the cytoplasm to nucleus in stimulated RAW 264.7 cells. Girinimbine was also shown to have considerable antioxidant activity whereby 20 µg/mL of girinimbine was equivalent to 82.17±1.88 µM of Trolox. In mice with carrageenan-induced peritonitis, oral pretreatment with girinimbine helped limit total leukocyte migration (mainly of neutrophils, and reduced pro-inflammatory cytokine levels (interleukin-1beta and tumor necrosis factor-alpha in the peritoneal fluid. These findings strongly suggest that girinimbine could act as a chemopreventive and/or chemotherapeutic agent by inducing apoptosis while suppressing inflammation. There is a potential for girinimbine to be further investigated for its applicability in treating early stages of cancer. Keywords: carbazole alkaloid, apoptosis, inflammation, chemopreventive, chemotherapeutic

  4. Protein-coated pH-responsive gold nanoparticles: Microwave-assisted synthesis and surface charge-dependent anticancer activity

    Directory of Open Access Journals (Sweden)

    Dickson Joseph

    2014-09-01

    Full Text Available The biocompatibility and ease of functionalization of gold nanoparticles underlie significant potential in biotechnology and biomedicine. Eight different proteins were examined in the preparation of gold nanoparticles (AuNPs in aqueous medium under microwave irradiation. Six of the proteins resulted in the formation of AuNPs. The intrinsic pH of the proteins played an important role in AuNPs with strong surface plasmon bands. The hydrodynamic size of the nanoparticles was larger than the values observed by TEM and ImageJ. The formation of a protein layer on the AuNPs accounts for this difference. The AuNPs exhibited sensitivity towards varying pH conditions, which was confirmed by determining the difference in the isoelectric points studied by using pH-dependent zeta potential titration. Cytotoxicity studies revealed anticancerous effects of the AuNPs at a certain micromolar concentration by constraining the growth of cancer cells with different efficacies due to the use of different proteins as capping agents. The positively charged AuNPs are internalized by the cells to a greater level than the negatively charged AuNPs. These AuNPs synthesized with protein coating holds promise as anticancer agents and would help in providing a new paradigm in area of nanoparticles.

  5. Cytosolic Cl- Affects the Anticancer Activity of Paclitaxel in the Gastric Cancer Cell Line, MKN28 Cell

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    Sachie Tanaka

    2017-05-01

    Full Text Available Background/Aims: Our previous study revealed that cytosolic Cl- affected neurite elongation promoted via assembly of microtubule in rat pheochromocytoma PC12D cells and Cl-–induced blockade of intrinsic GTPase enhanced tubulin polymerization in vitro. Paclitaxel (PTX is a microtubule-targeted chemotherapeutic drug and stabilizes microtubules resulting in mainly blockade of mitosis at the metaphase-anaphase transition and induction of apoptosis. In the present study, we tried to clarify whether the cytosolic Cl- affected PTX ability to inhibit cell growth in the gastric cancer cell line, MKN28. Methods: To clarify the cytosolic Cl- action on PTX-induced cell death and metaphase-anaphase transition in the gastric cancer cell line, MKN28 cell, and PTX-induced tubulin polymerization, we performed cell proliferation assay, cytosolic Cl- concentration measurement, immunofluorescence microscopy, and in vitro tubulin polymerization assay. Results: The decline of cytosolic Cl- weakened the cytotoxic effect of PTX on cell proliferation of MKN28 cells, which could pass through the metaphase-anaphase transition. Moreover, in vitro PTX-induced tubulin polymerization was diminished under the low Cl- condition. Conclusions: Our results strongly suggest that the upregulation of cytosolic Cl- concentration would enhance the antitumor effect of PTX, and that the cytosolic Cl- would be one of the key targets for anti-cancer therapy.

  6. Selective anticancer activity of a hexapeptide with sequence homology to a non-kinase domain of Cyclin Dependent Kinase 4

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    Agarwala Usha

    2011-06-01

    Full Text Available Abstract Background Cyclin-dependent kinases 2, 4 and 6 (Cdk2, Cdk4, Cdk6 are closely structurally homologous proteins which are classically understood to control the transition from the G1 to the S-phases of the cell cycle by combining with their appropriate cyclin D or cyclin E partners to form kinase-active holoenzymes. Deregulation of Cdk4 is widespread in human cancer, CDK4 gene knockout is highly protective against chemical and oncogene-mediated epithelial carcinogenesis, despite the continued presence of CDK2 and CDK6; and overexpresssion of Cdk4 promotes skin carcinogenesis. Surprisingly, however, Cdk4 kinase inhibitors have not yet fulfilled their expectation as 'blockbuster' anticancer agents. Resistance to inhibition of Cdk4 kinase in some cases could potentially be due to a non-kinase activity, as recently reported with epidermal growth factor receptor. Results A search for a potential functional site of non-kinase activity present in Cdk4 but not Cdk2 or Cdk6 revealed a previously-unidentified loop on the outside of the C'-terminal non-kinase domain of Cdk4, containing a central amino-acid sequence, Pro-Arg-Gly-Pro-Arg-Pro (PRGPRP. An isolated hexapeptide with this sequence and its cyclic amphiphilic congeners are selectively lethal at high doses to a wide range of human cancer cell lines whilst sparing normal diploid keratinocytes and fibroblasts. Treated cancer cells do not exhibit the wide variability of dose response typically seen with other anticancer agents. Cancer cell killing by PRGPRP, in a cyclic amphiphilic cassette, requires cells to be in cycle but does not perturb cell cycle distribution and is accompanied by altered relative Cdk4/Cdk1 expression and selective decrease in ATP levels. Morphological features of apoptosis are absent and cancer cell death does not appear to involve autophagy. Conclusion These findings suggest a potential new paradigm for the development of broad-spectrum cancer specific therapeutics with

  7. In Vitro and in Vivo Anticancer Activity of Pardaxin against Proliferation and Growth of Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yifan Han

    2015-12-01

    Full Text Available Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH, a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin painting remain undetermined. Additionally, the toxic effects of pardaxin on normal tissue remain unclear. The present study investigated the anticancer activity of pardaxin in oral squamous cell carcinoma (OSCC cells in the hamster buccal pouch model with or without 7,12-dimethylbenz[a]anthracene (DMBA pretreatment. This is the first study to confirm the effects of pardaxin on normal tissue and its nontoxic effects in vivo. Cell viability assays and colony formation tests in OSCC cell lines (SCC-4 demonstrated that pardaxin reduced cell viability in a dose-dependent manner. Immunofluorescence staining of cleaved caspase-3 in SCC-4 cells revealed that expression of activated caspase-3 in SCC-4 cells significantly increased after 24-h treatment with pardaxin. Additionally, a cell cycle analysis indicated that pardaxin treatment resulted in the cell cycle arrest of SCC-4 cells in the G2/M phase, thereby limiting cell proliferation. Furthermore, pardaxin treatment substantially alleviated carcinogenesis in the DMBA-induced hamster buccal pouch model by lowering prostaglandin E2 levels. These results suggest that pardaxin is a potential marine drug for adjuvant chemotherapy for human OSCC and oral cancer.

  8. Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

    International Nuclear Information System (INIS)

    Cervelli, Manuela; Grillo, Rosalba; Woster, Patrick M; Casero, Robert A Jr; Mariottini, Paolo; Bellavia, Gabriella; Fratini, Emiliano; Amendola, Roberto; Polticelli, Fabio; Barba, Marco; Federico, Rodolfo; Signore, Fabrizio; Gucciardo, Giacomo

    2010-01-01

    Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials

  9. Spermine oxidase (SMO activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

    Directory of Open Access Journals (Sweden)

    Gucciardo Giacomo

    2010-10-01

    Full Text Available Abstract Background Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC. This study investigates the expression of spermine oxidase (SMO and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. Methods BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Results Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. Conclusions This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials.

  10. Extracts and compounds with anti-diabetic complications and anti-cancer activity from Castanea mollissina Blume (Chinese chestnut).

    Science.gov (United States)

    Zhang, Lin; Gao, Hui-yuan; Baba, Masaki; Okada, Yoshihito; Okuyama, Toru; Wu, Li-jun; Zhan, Li-bin

    2014-10-28

    Castanea mollissima Blume (Chinese chestnut), as a food product is known for its various nutrients and functional values to the human health. The present study was carried out to analyze the anti-diabetic complications and anti-cancer activities of the bioactive compounds present in C. mollissima. The kernels (CK), shells (CS) and involucres (CI) parts of C. Blume were extracted with 90% alcohol. The water suspension of these dried alcohol extracts were extracted using EtOAc and n-BuOH successively. The n-BuOH fraction of CI (CI-B) was isolated by silica gel column, Sephadex LH 20 column and preparative HPLC. The isolated compounds were identified by 1H-NMR, 13C-NMR, HMBC, HMQC and ESI-Q-TOF MS, All the fractions and compounds isolated were evaluated on human recombinant aldose reductase (HR-AR) assay, advanced glycation end products (AGEs) formation assay and human COLO 320 DM colon cancer cells inhibitory assay. CI-B was found to show a significant inhibitory effect in above biological screenings. Six flavonoids and three polyphenolic acids were obtained from CI-B. They were identified as kaempferol (1), kaempferol-3-O-[6''-O-(E)-p-coumaroyl]-β-D-glucopyranoside (2), kaempferol-3-O-[6''-O-(E)-p-coumaroyl]-β-D-galactopyranoside (3), kaempferol-3-O-[2''-O-(E)-p-coumaroyl]-β-D-glucopyranoside (4), kaempferol-3-O-[2", 6"-di-O-(E)-p-coumaroyl]-β-D-glucopyranoside (5) and kaempferol-3-O-[2", 6"-di-O-(E)-p-coumaroyl]-β-D-galactopyranoside (6), casuariin (7), casuarinin (8) and castalagin (9). Compounds 2-9 were found to show higher activity than quercetin (positive control) in the AR assay. Compounds 3-6, 8, and 9 showed stronger inhibitory effects than amino guanidine (positive control) on AGEs production. Compounds 4-6, 7, and 8 showed much higher cytotoxic activity than 5-fluorouracil (positive control) against the human COLO 320 DM colon cancer cells. Our results suggest that flavonoids and polyphenolic acids possesses anti-diabetes complications and anti-cancer

  11. Synthesis of New Thiazole Derivatives Bearing A Sulfonamide Moiety Of Expected Anticancer And Radiosensitizing Activities

    International Nuclear Information System (INIS)

    Mohamed, S.Sh.I.

    2012-01-01

    In a search for new cytotoxic agents with improved antitumor activity and selectivity, some new pyrano thiazole and thiazolopyranopyrimidine derivatives bearing sulfonamide moiety were synthesized. The newly synthesized compounds were evaluated for their antitumor activity alone and in combination with γ-irradiation. These new compounds were docked inside the active site of carbonic anhydrase II to predict their mechanism of action.

  12. Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest

    Science.gov (United States)

    Tarade, Daniel; Ma, Dennis; Pignanelli, Christopher; Mansour, Fadi; Simard, Daniel; van den Berg, Sean; Gauld, James; McNulty, James; Pandey, Siyaram

    2017-01-01

    The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents. PMID:28253265

  13. Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest.

    Directory of Open Access Journals (Sweden)

    Daniel Tarade

    Full Text Available The cis-stilbene, combretastatin A4 (CA4, is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents.

  14. Disruption of mitochondrial function as mechanism for anti-cancer activity of a novel mitochondriotropic menadione derivative.

    Science.gov (United States)

    Teixeira, José; Amorim, Ricardo; Santos, Katia; Soares, Pedro; Datta, Sandipan; Cortopassi, Gino A; Serafim, Teresa L; Sardão, Vilma A; Garrido, Jorge; Borges, Fernanda; Oliveira, Paulo J

    2018-01-15

    Menadione, also known as vitamin K 3 , is a 2-methyl-1,4 naphthoquinone with a potent cytotoxic activity mainly resulting from its quinone redox-cycling with production of reactive oxygen species (ROS). Although increased ROS generation is considered a relevant mechanism in cancer cell death, it may not be sufficiently effective to kill cancer cells due to phenotypic adaptations. Therefore, combining ROS-generating agents with other molecules targeting important cancer cell phenotypes can be an effective therapeutic strategy. As mitochondrial dysfunction has been implicated in many human diseases, including cancer, we describe here the discovery of a mitochondrial-directed agent (MitoK 3 ), which was developed by conjugating a TPP cation to the C3 position of the menadione's naphthoquinone ring, increasing its selective accumulation in mitochondria, as well as led to alterations of its redox properties and consequent biological outcome. MitoK 3 disturbed the mitochondrial bioenergetic apparatus, with subsequent loss of mitochondrial ATP production. The combinatory strategy of MitoK 3 with anticancer agent doxorubicin (DOX) resulted in a degree of cytotoxicity higher than those of the individual molecules, as the combination triggered tumour apoptotic cell death evident by caspase 3/9 activities, probably through mitochondrial destabilization or by interference with mitochondrial redox processes. The results of this investigation support the importance of drug discovery process in developing molecules that can be use as adjuvant therapy in patients with specific cancer subtypes. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Anticancer Activity of a Hexapeptide from Skate (Raja porosa) Cartilage Protein Hydrolysate in HeLa Cells.

    Science.gov (United States)

    Pan, Xin; Zhao, Yu-Qin; Hu, Fa-Yuan; Chi, Chang-Feng; Wang, Bin

    2016-08-16

    In this study, the hexapeptide Phe-Ile-Met-Gly-Pro-Tyr (FIMGPY), which has a molecular weight of 726.9 Da, was separated from skate (Raja porosa) cartilage protein hydrolysate using ultrafiltration and chromatographic methods, and its anticancer activity was evaluated in HeLa cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay indicated that FIMGPY exhibited high, dose-dependent anti-proliferation activities in HeLa cells with an IC50 of 4.81 mg/mL. Acridine orange/ethidium bromide (AO/EB) fluorescence staining and flow cytometry methods confirmed that FIMGPY could inhibit HeLa cell proliferation by inducing apoptosis. Western blot assay revealed that the Bax/Bcl-2 ratio and relative intensity of caspase-3 in HeLa cells treated with 7-mg/mL FIMGPY were 2.63 and 1.83, respectively, significantly higher than those of the blank control (p skate cartilage protein hydrolysate may have applications as functional foods and nutraceuticals for the treatment and prevention of cancer.

  16. In Vitro Anticancer Activity of the Crude Extract and two Dicinnamate Isolates from the Jamaican Ball Moss (Tillandsia Recurvata L.).

    Science.gov (United States)

    Lowe, Henry Ic; Toyang, Ngeh J; Watson, Charah; Badal, Simone; Bahado-Singh, Perceval; Bryant, Joseph

    2013-01-01

    A crude chloroform extract from the Jamaican Ball Moss (Tillandsia recurvata L.) was tested for activity against three human cancer cell lines including; A375 (human melanoma), MCF-7 (human breast) and PC-3 (human prostate cancer) using the WST-1 assay. IC 50 s obtained against these cell lines; A375, MCF-7 and PC-3 in the presence of the crude extract are; 0.9μg/ml, 40.51μg/ml and 5.97μg/ml respectively indicating the promising anti-cancer activity of the ball moss extract. Further, preliminary phytochemical study was conducted in an attempt to identify and isolate the phytochemicals that could possibly be responsible for the observed bioactivity of the ball moss chloroform extract. As a result, two dicinnamates were isolated; 1,3-di-O-Cinnamoyl-glycerol ( 1 ) and (E)-3-(cinnamoyloxy)-2-hydroxypropyl 3-(3,4-dimethoxyphenyl)acrylate ( 2 ) and we report for the first time isolation of compound 2 . Even though the bioactivity of these two islaotes were fairly weak against the cell lines, the results presented here will prove useful for further research aimed at identifying molecules that maybe effective against melanoma, breast and prostate cancers associated with fewer side-effects.

  17. Study of anticancer and antibacterial activities of Foeniculum vulgare, Justicia adhatoda and Urtica dioica as natural curatives.

    Science.gov (United States)

    Batool, R; Salahuddin, H; Mahmood, T; Ismail, M

    2017-09-30

    High-throughput technologies, such as synthetic biology and genomics have paved new paths for discovery and utility of medicinally beneficial plants. Bioactive molecules isolated from different plants have significantly higher biological activities. The present study was done to analyze antibacterial potential of some medicinal plants against multi drug resistant (MDR) pathogens and anticancer effect against MCF-7 cell line. Methanolic and ethanolic extracts were tested for their antibacterial activity by disc diffusion method against six MDR bacterial strains and for cytotoxicity evaluation by MTT assay. Ethanolic extracts of the three tested plants exhibited growth inhibitory effect against Klebsiella pneumonia, Serratia marcescens and Methicillin-resistant S. aureus. Pseudomonas aeruginosa was more resistant to all extracts as its growth was least inhibited by the extracts of all tested plants. Ethanol extract of Foeniculum vulgare exhibited significant inhibition of cancer cells proliferation. Methanol extract of Justicia adhatoda also showed considerable inhibition of cancer cells. Future studies must converge on detailed investigation of modes of action of extracts of tested plants.

  18. Chemical composition and anticancer activity of essential oils of Mediterranean sage (Salvia officinalis L.) grown in different environmental conditions.

    Science.gov (United States)

    Russo, Alessandra; Formisano, Carmen; Rigano, Daniela; Senatore, Felice; Delfine, Sebastiano; Cardile, Venera; Rosselli, Sergio; Bruno, Maurizio

    2013-05-01

    Salvia officinalis L. can be found worldwide and its leaves are commonly used as ingredient in food industry. Sage essential oil is applied in the treatment of a range of diseases and has been shown to possess different biological activities. The objectives of our research were to study the effects of environment on crop, chemical composition and anticancer activity on S. officinalis essential oil. Sage was cultivated at eighteen experimental sites in south-central Italy (Molise) in different growing environments. The essential oils (S1-S18), extracted by hydrodistillation, were analyzed by GC and CG/MS. Results show that the main components were α-thujone, camphor, borneol, γ-muurolene and sclareol for all the samples, but the percentages of these compounds varied depending on environmental factors such as altitude, water availability and pedo-climatic conditions. The growth-inhibitory and proapoptotic effects of the eighteen sage essential oils were evaluated in three human melanoma cell lines, A375, M14, and A2058. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Shang Weihu

    2011-12-01

    Full Text Available Abstract Background Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU. Methods Components of TC extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA. Results TC extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell growth by inducing apoptosis and G2/M cell cycle arrest. Most interestingly, TC extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells in vitro, with Combination Index values (CI ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI TC extract did not affect the pharmacokinetics of 5-FU in rats. Conclusions The combinational use of the TC extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.

  20. Developments in platinum anticancer drugs

    Science.gov (United States)

    Tylkowski, Bartosz; Jastrząb, Renata; Odani, Akira

    2018-01-01

    Platinum compounds represent one of the great success stories of metals in medicine. Following the unexpected discovery of the anticancer activity of cisplatin (Fig. 1) in 1965 by Prof. Rosenberg [1], a large number of its variants have been prepared and tested for their ability to kill cancer cells and inhibit tumor growth. Although cisplatin has been in use for over four decades, new and more effective platinum-based therapeutics are finally on the horizon. A wide introduction to anticancer studies is given by the authors of the previous chapter. This chapter aims at providing the readers with a comprehensive and in-depth understanding of recent developments of platinum anticancer drugs and to review the state of the art. The chapter is divided into two parts. In the first part we present a historical aspect of platinum and its complexes, while in the second part we give an overview of developments in the field of platinum anticancer agents.

  1. Novel 1,3,4-Oxadiazole Induces Anticancer Activity by Targeting NF-κB in Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chakrabhavi Dhananjaya Mohan

    2018-03-01

    Full Text Available Aberrant activation of NF-κB is linked with the progression of human malignancies including hepatocellular carcinoma (HCC, and blockade of NF-κB signaling could be a potential target in the treatment of several cancers. Therefore, designing of novel small molecule inhibitors that target NF-κB activation is of prime importance in the treatment of several cancers. In the present work, we report the synthesis of series of 1,3,4-oxadiazoles, investigated their anticancer potential against HCC cells, and identified 2-(3-chlorobenzo[b]thiophen-2-yl-5-(3-methoxyphenyl-1,3,4-oxadiazole (CMO as the lead compound. Further, we examined the effect of CMO on cell cycle distribution (flow cytometry, apoptosis (annexin V-propidium iodide-FITC staining, and phosphorylation of NF-κB signaling pathway proteins (IκB and p65 in HCC cells. We found that CMO induced antiproliferative effect in dose- and time-dependent manner. Also, CMO significantly increased the percentage of sub-G1 cell population and induced apoptosis. Furthermore, CMO found to decrease the phosphorylation of IκB (Ser 32 in the cytoplasmic extract and p65 (Ser 536 in the nuclear extract of HCC cells. It also abrogated the DNA binding ability and transcriptional activity of NF-κB. CMO induced the cleavage of PARP and caspase-3 in a time-dependent manner. In addition, transfection with p65 small interfering RNA blocks CMO-induced caspase-3/7 activation. Molecular docking analysis revealed that CMO interacts with the hydrophobic region of p65 protein. Thus, we are reporting CMO as an inhibitor of NF-κB signaling pathway.

  2. The anticancer activity of lytic peptides is inhibited by heparan sulfate on the surface of the tumor cells

    Science.gov (United States)

    2009-01-01

    Background Cationic antimicrobial peptides (CAPs) with antitumor activity constitute a promising group of novel anticancer agents. These peptides induce lysis of cancer cells through interactions with the plasma membrane. It is not known which cancer cell membrane components influence their susceptibility to CAPs. We have previously shown that CAPs interact with the two glycosaminoglycans (GAGs), heparan sulfate (HS) and chondroitin sulfate (CS), which are present on the surface of most cells. The purpose of this study was to investigate the role of the two GAGs in the cytotoxic activity of CAPs. Methods Various cell lines, expressing different levels of cell surface GAGs, were exposed to bovine lactoferricin (LfcinB) and the designer peptide, KW5. The cytotoxic effect of the peptides was investigated by use of the colorimetric MTT viability assay. The cytotoxic effect on wild type CHO cells, expressing normal amounts of GAGs on the cell surface, and the mutant pgsA-745, that has no expression of GAGs on the cell surface, was also investigated. Results We show that cells not expressing HS were more susceptible to CAPs than cells expressing HS at the cell surface. Further, exogenously added heparin inhibited the cytotoxic effect of the peptides. Chondroitin sulfate had no effect on the cytotoxic activity of KW5 and only minor effects on LfcinB cytotoxicity. Conclusion Our results show for the first time that negatively charged molecules at the surface of cancer cells inhibit the cytotoxic activity of CAPs. Our results indicate that HS at the surface of cancer cells sequesters CAPs away from the phospholipid bilayer and thereby impede their ability to induce cytolysis. PMID:19527490

  3. Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against Plasmodium and Trypanosoma parasites.

    Science.gov (United States)

    Engel, Jessica A; Jones, Amy J; Avery, Vicky M; Sumanadasa, Subathdrage D M; Ng, Susanna S; Fairlie, David P; Skinner-Adams, Tina; Andrews, Katherine T

    2015-12-01

    Histone deacetylase (HDAC) enzymes work together with histone acetyltransferases (HATs) to reversibly acetylate both histone and non-histone proteins. As a result, these enzymes are involved in regulating chromatin structure and gene expression as well as other important cellular processes. HDACs are validated drug targets for some types of cancer, with four HDAC inhibitors clinically approved. However, they are also showing promise as novel drug targets for other indications, including malaria and other parasitic diseases. In this study the in vitro activity of four anti-cancer HDAC inhibitors was examined against parasites that cause malaria and trypanosomiasis. Three of these inhibitors, suberoylanilide hydroxamic acid (SAHA; vorinostat(®)), romidepsin (Istodax(®)) and belinostat (Beleodaq(®)), are clinically approved for the treatment of T-cell lymphoma, while the fourth, panobinostat, has recently been approved for combination therapy use in certain patients with multiple myeloma. All HDAC inhibitors were found to inhibit the growth of asexual-stage Plasmodium falciparum malaria parasites in the nanomolar range (IC50 10-200 nM), while only romidepsin was active at sub-μM concentrations against bloodstream form Trypanosoma brucei brucei parasites (IC50 35 nM). The compounds were found to have some selectivity for malaria parasites compared with mammalian cells, but were not selective for trypanosome parasites versus mammalian cells. All compounds caused hyperacetylation of histone and non-histone proteins in P. falciparum asexual stage parasites and inhibited deacetylase activity in P. falciparum nuclear extracts in addition to recombinant PfHDAC1 activity. P. falciparum histone hyperacetylation data indicate that HDAC inhibitors may differentially affect the acetylation profiles of histone H3 and H4.

  4. The anticancer activity of lytic peptides is inhibited by heparan sulfate on the surface of the tumor cells

    Directory of Open Access Journals (Sweden)

    Rekdal Øystein

    2009-06-01

    Full Text Available Abstract Background Cationic antimicrobial peptides (CAPs with antitumor activity constitute a promising group of novel anticancer agents. These peptides induce lysis of cancer cells through interactions with the plasma membrane. It is not known which cancer cell membrane components influence their susceptibility to CAPs. We have previously shown that CAPs interact with the two glycosaminoglycans (GAGs, heparan sulfate (HS and chondroitin sulfate (CS, which are present on the surface of most cells. The purpose of this study was to investigate the role of the two GAGs in the cytotoxic activity of CAPs. Methods Various cell lines, expressing different levels of cell surface GAGs, were exposed to bovine lactoferricin (LfcinB and the designer peptide, KW5. The cytotoxic effect of the peptides was investigated by use of the colorimetric MTT viability assay. The cytotoxic effect on wild type CHO cells, expressing normal amounts of GAGs on the cell surface, and the mutant pgsA-745, that has no expression of GAGs on the cell surface, was also investigated. Results We show that cells not expressing HS were more susceptible to CAPs than cells expressing HS at the cell surface. Further, exogenously added heparin inhibited the cytotoxic effect of the peptides. Chondroitin sulfate had no effect on the cytotoxic activity of KW5 and only minor effects on LfcinB cytotoxicity. Conclusion Our results show for the first time that negatively charged molecules at the surface of cancer cells inhibit the cytotoxic activity of CAPs. Our results indicate that HS at the surface of cancer cells sequesters CAPs away from the phospholipid bilayer and thereby impede their ability to induce cytolysis.

  5. Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against Plasmodium and Trypanosoma parasites

    Directory of Open Access Journals (Sweden)

    Jessica A. Engel

    2015-12-01

    Full Text Available Histone deacetylase (HDAC enzymes work together with histone acetyltransferases (HATs to reversibly acetylate both histone and non-histone proteins. As a result, these enzymes are involved in regulating chromatin structure and gene expression as well as other important cellular processes. HDACs are validated drug targets for some types of cancer, with four HDAC inhibitors clinically approved. However, they are also showing promise as novel drug targets for other indications, including malaria and other parasitic diseases. In this study the in vitro activity of four anti-cancer HDAC inhibitors was examined against parasites that cause malaria and trypanosomiasis. Three of these inhibitors, suberoylanilide hydroxamic acid (SAHA; vorinostat®, romidepsin (Istodax® and belinostat (Beleodaq®, are clinically approved for the treatment of T-cell lymphoma, while the fourth, panobinostat, has recently been approved for combination therapy use in certain patients with multiple myeloma. All HDAC inhibitors were found to inhibit the growth of asexual-stage Plasmodium falciparum malaria parasites in the nanomolar range (IC50 10–200 nM, while only romidepsin was active at sub-μM concentrations against bloodstream form Trypanosoma brucei brucei parasites (IC50 35 nM. The compounds were found to have some selectivity for malaria parasites compared with mammalian cells, but were not selective for trypanosome parasites versus mammalian cells. All compounds caused hyperacetylation of histone and non-histone proteins in P. falciparum asexual stage parasites and inhibited deacetylase activity in P. falciparum nuclear extracts in addition to recombinant PfHDAC1 activity. P. falciparum histone hyperacetylation data indicate that HDAC inhibitors may differentially affect the acetylation profiles of histone H3 and H4.

  6. Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery: an in vitro investigation on human breast cancer and leukemia cell lines.

    Science.gov (United States)

    Foglietta, Federica; Serpe, Loredana; Canaparo, Roberto; Vivenza, Nicoletta; Riccio, Giovanna; Imbalzano, Erica; Gasco, Paolo; Zara, Gian Paolo

    2014-01-01

    Histone modification has emerged as a promising approach to cancer therapy. The short-chain fatty acid, butyric acid, a histone deacetylase (HD) inhibitor, has shown anticancer activity. Butyrate transcriptional activation is indeed able to withdraw cancer cells from the cell cycle, leading to programmed cell death. Since butyrate's clinical use is hampered by unfavorable pharmacokinetic and pharmacodynamic properties, delivery systems, such as solid lipid nanoparticles (SLN), have been developed to overcome these constraints. In order to outline the influence of butyrate delivery on its anticancer activity, the effects of butyrate as a free (sodium butyrate, NB) or nanoparticle (cholesteryl butyrate solid lipid nanoparticles, CBSLN) formulation on the growth of different human cancer cell lines, such as the promyelocytic leukemia, HL-60, and the breast cancer, MCF-7 was investigated. A detailed investigation into the mechanism of the induced cytotoxicity was also carried out, with a special focus on the modulation of HD and cyclin-dependent kinase (CDK) mRNA gene expression by real time PCR analysis. In HL-60 cells, CBSLN induced a higher and prolonged expression level of the butyrate target genes at lower concentrations than NB. This led to a significant decrease in cell proliferation, along with considerable apoptosis, cell cycle block in the G0/G1 phase, significant inhibition of total HD activity and overexpression of the p21 protein. Conversely, in MCF-7 cells, CBSLN did not enhance the level of expression of the butyrate target genes, leading to the same anticancer activity as that of NB. Solid lipid nanoparticles were able to improve butyrate anticancer activity in HL-60, but not in MCF-7 cells. This is consistent with difference in properties of the cells under study, such as expression of the TP53 tumor suppressor, or the transporter for short-chain fatty acids, SLC5A8.

  7. Data supporting the anticancer activity of posterior salivary gland (PSG toxin from the cuttlefish Sepia pharaonis Ehrenberg (1831

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    Ramachandran Karthik

    2017-08-01

    Full Text Available The data presented illustrated the in vitro anti-proliferative effect of the PSG toxin from the cuttlefish, Sepia pharaonis. The cytostatic potentials of the PSG toxin were determined by the lymphocyte migration inhibition assay. The PSG toxin (50 μg/ml exhibited commendable inhibition of the migration of lymphocytes across the agarose gel matrix under the presence of lipopolysaccharide mitogen, with a mean migration index of 0.625. The cytotoxicity of the PSG toxin against selected cancer cell lines was determined using the MTT assay. The PSG toxin exhibited dose-dependent cytotoxicity against the MCF-7 breast cancer cells followed by KB (oral, HeLa (cervical and A549 (lung cancer cell lines. The PSG toxin also exhibited proportional release of LDH leakage by mitochondrial damage with an IC50 of 13.85 μM against MCF-7 breast cancer cells. The in vitro anticancer activity of the PSG toxin against the selected cell lines was evaluated by Karthik et al. (2017 [1].

  8. Modulating chromatin structure and DNA accessibility by deacetylase inhibition enhances the anti-cancer activity of silver nanoparticles.

    Science.gov (United States)

    Igaz, Nóra; Kovács, Dávid; Rázga, Zsolt; Kónya, Zoltán; Boros, Imre M; Kiricsi, Mónika

    2016-10-01

    Histone deacetylase (HDAC) inhibitors are considered as novel therapeutic agents inducing cell cycle arrest and apoptotic cell death in various cancer cells. Inhibition of deacetylase activity results in a relaxed chromatin structure thereby rendering the genetic material more vulnerable to DNA targeting agents that could be exploited by combinational cancer therapy. The unique potential of silver nanoparticles (AgNPs) in tumor therapy relies on the generation of reactive radicals which trigger oxidative stress, DNA damage and apoptosis in cancer cells. The revolutionary application of AgNPs as chemotherapeutical drugs seems very promising, nevertheless the exact molecular mechanisms of AgNP action in combination with other anti-cancer agents have yet to be elucidated in details before clinical administrations. As a step towards this we investigated the combinational effect of HDAC inhibition and AgNP administration in HeLa cervical cancer cells. We identified synergistic inhibition of cancer cell growth and migration upon combinational treatments. Here we report that the HDAC inhibitor Trichostatin A enhances the DNA targeting capacity and apoptosis inducing efficacy of AgNPs most probably due to its effect on chromatin condensation. These results point to the potential benefits of combinational application of HDAC inhibitors and AgNPs in novel cancer medication protocols. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Aquation Is a Crucial Activation Step for Anticancer Action of Ruthenium(II) Polypyridyl Complexes to Trigger Cancer Cell Apoptosis.

    Science.gov (United States)

    Li, Meng; Lai, Lanhai; Zhao, Zhennan; Chen, Tianfeng

    2016-01-01

    Aquation has been proposed as crucial chemical action step for ruthenium (Ru) complexes, but its effects on the action mechanisms remain elusive. Herein, we have demonstrated the aquation process of a potent Ru polypyridyl complex (RuBmp=[Ru(II) (bmbp)(phen)Cl]ClO4 , bmbp=2,6-bis(6-methylbenzimidazol-2-yl) pyridine, phen=phenanthroline) with a chloride ligand, and revealed that aquation of RuBmp effectively enhanced its hydrophilicity and cellular uptake, thus significantly increasing its anticancer efficacy. The aquation products (H-RuBmp=[Ru(II) (bmbp)(phen)Cl]ClO4 , [Ru(II) (bmbp)(phen)(H2 O)]ClO4 , bmbp) exhibited a much higher apoptosis-inducing ability than the intact complex, with involvement of caspase activation, mitochondria dysfunction, and interaction with cell membrane death receptors. H-RuBmp demonstrated a higher interaction potency with the cell membrane and induced higher levels of ROS overproduction in cancer cells to regulate the AKT, MAPK, and p53 signaling pathways. Taken together, this study could provide useful information for fine-tuning the rational design of next-generation metal medicines. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Anticancer activity of synthetic bis(indolyl)methane-ortho-biaryls against human cervical cancer (HeLa) cells.

    Science.gov (United States)

    Jamsheena, Vellekkatt; Shilpa, Ganesan; Saranya, Jayaram; Harry, Nissy Ann; Lankalapalli, Ravi Shankar; Priya, Sulochana

    2016-03-05

    Bis(indolyl)methane appended biaryls were designed, synthesized and evaluated in human cervical cancer cell lines (HeLa) for their anticancer activities and compared against normal rat cardiac myoblasts (H9C2) cells. Compounds 1-12 were synthesized, with variations in one of the phenyl unit, in a single step by condensation of biaryl-2-carbaldehydes with indole in the presence of para-toluenesulfonic acid. Compound 1 exhibited a GI50 value of 11.00 ± 0.707 μM and the derivatives, compounds 4 and 11 showed a GI50 value of 8.33 ± 0.416 μM and 9.13 ± 0.177 μM respectively in HeLa cells and was found to be non-toxic to H9C2 cells up to 20 μM. Furthermore, compounds 1, 4 and 11 induced caspase dependent cellular apoptosis in a concentration-dependent manner, reduced mitochondrial membrane potential, inhibited the cell migration and downregulated the production of MMP-2 and MMP-9 in HeLa cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Comparison of anticancer activities of Korean Red Ginseng-derived fractions

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    Kwang-Soo Baek

    2017-07-01

    Conclusion: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.

  12. Antimicrobial and anticancer activity and DNA fingerprinting of extracts from Red Sea marine fungal symbiotes.

    OpenAIRE

    Asma Alsed; Marwa M. Azab; Amany K. Ibrahim

    2016-01-01

    Marine microorganisms have become an important source of pharmacologically active metabolites. More specifically, fungi from the marine environment have shown great potential as suggested by the diversity of secondary metabolites. The aim of this study was to look for bioactive natural products from Red Sea derived fungi. Numerous natural products with novel structures and distinct biological activities have been discovered as the secondary metabolites of marine- derived microbes....

  13. Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cells.

    Science.gov (United States)

    Teixeira, Ricardo G; Brás, Ana Rita; Côrte-Real, Leonor; Tatikonda, Rajendhraprasad; Sanches, Anabela; Robalo, M Paula; Avecilla, Fernando; Moreira, Tiago; Garcia, M Helena; Haukka, Matti; Preto, Ana; Valente, Andreia

    2018-01-01

    Three new compounds have been synthesized and completely characterized by analytical and spectroscopic techniques. The new bipyridine-perfluorinated ligand L1 and the new organometallic complex [Ru(η 5 -MeCp)(PPh 3 ) 2 Cl] (Ru1) crystalize in the centrosymmetric triclinic space group P1¯. Analysis of the phenotypic effects induced by both organometallic complexes Ru1 and [Ru(η 5 -MeCp)(PPh 3 )(L1)][CF 3 SO 3 ] (Ru2), on human colorectal cancer cells (SW480 and RKO) survival, showed that Ru2 has a potent anti-proliferative activity, 4-6 times higher than cisplatin, and induce apoptosis in these cells. Data obtained in a noncancerous cell line derived from normal colon epithelial cells (NCM460) revealed an intrinsic selectivity of Ru2 for malignant cells at low concentrations, showing the high potential of this compound as a selective anticancer agent. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators.

    Science.gov (United States)

    Mignani, Serge; El Brahmi, Nabil; Eloy, Laure; Poupon, Joel; Nicolas, Valérie; Steinmetz, Anke; El Kazzouli, Said; Bousmina, Mosto M; Blanchard-Desce, Mireille; Caminade, Anne-Marie; Majoral, Jean-Pierre; Cresteil, Thierry

    2017-05-26

    A multivalent phosphorus dendrimer 1G 3 and its corresponding Cu-complex, 1G 3 -Cu have been recently identified as agents retaining high antiproliferative potency. This antiproliferative capacity was preserved in cell lines overexpressing the efflux pump ABC B1, whereas cross-resistance was observed in ovarian cancer cell lines resistant to cisplatin. Theoretical 3D models were constructed: the dendrimers appear as irregularly shaped disk-like nano-objects of about 22 Å thickness and 49 Å diameter, which accumulated in cells after penetration by endocytosis. To get insight in their mode of action, cell death pathways have been examined in human cancer cell lines: early apoptosis was followed by secondary necrosis after multivalent phosphorus dendrimers exposure. The multivalent plain phosphorus dendrimer 1G 3 moderately activated caspase-3 activity, in contrast with the multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu which strikingly reduced the caspase-3 content and activity. This decrease of caspase activity is not related to the presence of copper, since inorganic copper has no or little effect on caspase-3. Conversely the potent apoptosis activation could be related to a noticeable translocation of Bax to the mitochondria, resulting in the release of AIF into the cytosol, its translocation to the nucleus and a severe DNA fragmentation, without alteration of the cell cycle. The multivalent Cu-conjugated phosphorus dendrimer is more efficient than its non-complexed analog to activate this pathway in close relationship with the higher antiproliferative potency. Therefore, this multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu can be considered as a new and promising first-in-class antiproliferative agent with a distinctive mode of action, inducing apoptosis tumor cell death through Bax activation pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Bioinspired green synthesis of copper oxide nanoparticles from Syzygium alternifolium (Wt.) Walp: characterization and evaluation of its synergistic antimicrobial and anticancer activity

    Science.gov (United States)

    Yugandhar, Pulicherla; Vasavi, Thirumalanadhuni; Uma Maheswari Devi, Palempalli; Savithramma, Nataru

    2017-10-01

    In recent times, nanoparticles are attributed to green nanotechnology methods to know the synergistic biological activities. To accomplish this phenomenon, present study was aimed to synthesize copper oxide nanoparticles (CuO NPs) by using Syzygium alternifolium stem bark, characterized those NPs using expository tools and to elucidate high prioritized antimicrobial and anticancer activities. Synthesized particles exhibited a color change pattern upon synthesis and affirmed its respective broad peak at 285 nm which was analyzed through UV-vis spectroscopy. FT-IR study confirmed that phenols and primary amines were mainly involved in capping and stabilization of nanoparticles. DLS and Zeta potential studies revealed narrow size of particles with greater stability. XRD studies revealed the crystallographic nature of particles with 17.2 nm average size. Microscopic analysis by using TEM revealed that particle size range from 5-13 nm and most of them were spherical in shape, non-agglomerated and poly-dispersed in condition. Antimicrobial studies of particles showed highest inhibitory activity against E. coli and T. harzianum among bacterial and fungal strains, respectively. The scope of this study is extended by examining anticancer activity of CuO NPs. This study exhibited potential anticancer activity towards MDA-MB-231 human breast cancer lines. Overall, these examinations relate that the S. alternifolium is described as efficient well-being plant and probabilistically for the design and synthesis of nanoparticles for human health. This study paves a way to better understand antimicrobial and anticancer therapeutic drug potentials of nanoparticles to design and analysis of pharmaceuticals by in vivo and in vitro approaches.

  16. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma

    Science.gov (United States)

    2011-01-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent. PMID:21299897

  17. Chemical composition and anticancer and antioxidant activities of Schinus molle L. and Schinus terebinthifolius Raddi berries essential oils.

    Science.gov (United States)

    Bendaoud, Houcine; Romdhane, Mehrez; Souchard, Jean Pierre; Cazaux, Sylvie; Bouajila, Jalloul

    2010-08-01

    Essential oils were obtained by steam distillation from berries of Schinus molle L. and Schinus terebinthifolius Raddi originating from southern of Tunisia and analyzed by GC-FID and GC-MS. Among 57 and 62 compounds (%[mg/100 g dry matter]) identified in these oils, the main were alpha-phellandrene (46.52%[1256.15] and 34.38%[859.60]), beta-phellandrene (20.81%[561.74] and 10.61%[265.15]), alpha-terpineol (8.38%[226.26] and 5.60%[140.03]), alpha-pinene (4.34%[117.29] and 6.49%[162.25]), beta-pinene (4.96%[133.81] and 3.09%[77.30]) and p-cymene (2.49%[67.28] and 7.34%[183.40]), respectively. A marked quantity of gamma-cadinene (18.04%[451.05]) was also identified in the S. terebinthifolius essential oil whereas only traces (0.07%[1.81]) were detected in the essential oil of S. molle. The in vitro antioxidant and antiradical scavenging properties of the investigated essential oils were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Essential oil of S. terebinthifolius expressed stronger antioxidant activity in the ABTS assay, with an IC(50) of 24 +/- 0.8 mg/L, compared to S. molle (IC(50)= 257 +/- 10.3 mg/L). Essential oils were also evaluated for their anticancer activities against human breast cancer cells (MCF-7). S. terebinthifolius essential oil was more effective against tested cell lines (IC(50)= 47 +/- 9 mg/L) than that from S. molle (IC(50)= 54 +/- 10 mg/L). Suggestions on relationships between chemical composition and biological activities are outlined.

  18. Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity.

    Science.gov (United States)

    Shirakawa, Kotaro; Wang, Lan; Man, Na; Maksimoska, Jasna; Sorum, Alexander W; Lim, Hyung W; Lee, Intelly S; Shimazu, Tadahiro; Newman, John C; Schröder, Sebastian; Ott, Melanie; Marmorstein, Ronen; Meier, Jordan; Nimer, Stephen; Verdin, Eric

    2016-05-31

    Salicylate and acetylsalicylic acid are potent and widely used anti-inflammatory drugs. They are thought to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo-oxygenases, modulation of NF-κB activity, and direct activation of AMPK. However, the full spectrum of their activities is incompletely understood. Here we show that salicylate specifically inhibits CBP and p300 lysine acetyltransferase activity in vitro by direct competition with acetyl-Coenzyme A at the catalytic site. We used a chemical structure-similarity search to identify another anti-inflammatory drug, diflunisal, that inhibits p300 more potently than salicylate. At concentrations attainable in human plasma after oral administration, both salicylate and diflunisal blocked the acetylation of lysine residues on histone and non-histone proteins in cells. Finally, we found that diflunisal suppressed the growth of p300-dependent leukemia cell lines expressing AML1-ETO fusion protein in vitro and in vivo. These results highlight a novel epigenetic regulatory mechanism of action for salicylate and derivative drugs.

  19. Prazosin Displays Anticancer Activity against Human Prostate Cancers: Targeting DNA, Cell Cycle

    Directory of Open Access Journals (Sweden)

    Ssu-Chia Lin

    2007-10-01

    Full Text Available Quinazoline-based α1,-adrenoceptor antagonists, in particular doxazosin, terazosin, are suggested to display antineoplastic activity against prostate cancers. However, there are few studies elucidating the effect of prazosin. In this study, prazosin displayed antiproliferative activity superior to that of other α1-blockers, including doxazosin, terazosin, tamsulosin, phentolamine. Prazosin induced G2 checkpoint arrest, subsequent apoptosis in prostate cancer PC-3, DU-145, LNCaP cells. In p53-null PC-3 cells, prazosin induced an increase in DNA str, breaks, ATM/ATR checkpoint pathways, leading to the activation of downstream signaling cascades, including Cdc25c phosphorylation at Ser216, nuclear export of Cdc25c, cyclin-dependent kinase (Cdk 1 phosphorylation at Tyr15. The data, together with sustained elevated cyclin A levels (other than cyclin B1 levels, suggested that Cdki activity was inactivated by prazosin. Moreover, prazosin triggered mitochondria-mediated, caspaseexecuted apoptotic pathways in PC-3 cells. The oral administration of prazosin significantly reduced tumor mass in PC-3-derived cancer xenografts in nude mice. In summary, we suggest that prazosin is a potential antitumor agent that induces cell apoptosis through the induction of DNA damage stress, leading to Cdki inactivation, G2 checkpoint arrest. Subsequently, mitochondriamediated caspase cascades are triggered to induce apoptosis in PC-3 cells.

  20. Design, Synthesis and In Vitro Activity of Anticancer Styrylquinolines. The p53 Independent Mechanism of Action

    Czech Academy of Sciences Publication Activity Database

    Mrozek-Wilczkiewicz, A.; Spaczynska, E.; Malarz, K.; Cieslik, W.; Rams-Baron, M.; Kryštof, Vladimír; Musiol, R.

    2015-01-01

    Roč. 10, č. 11 (2015), e0142678 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : BIOLOGICAL-ACTIVITY SPECTRUM * MUTANT P53 * QUINOLINE DERIVATIVES Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

  1. Design, docking, synthesis and anticancer activity of some novel 2-(4-methylbenzenesulphonamidopentanedioic acid amide derivatives

    Directory of Open Access Journals (Sweden)

    Satyajit Dutta

    2014-08-01

    Full Text Available In the present work few novel 2-(4-methylbenzenesulphonamidopentanedioic acid amide derivatives and the basic compound 2-(4-methylphenylsulfon-amidopentanedioic acid have been designed, synthesized, characterized and screened for their possible antineoplastic activity both in vitro and in vivo. The modified drugs were docked against the protein histone deacetylase the energy value obtained was o-iodoanilide (-10.370504 and m-iodoanilide (-10.218276 of the titled compound. The in vitro activity was performed against five human cell lines like human breast cancer (MCF-7, leukemia (K-562, ova-rian cancer (OVACAR-3, human colon adenocarcinoma (HT-29 and Human kidney carcinoma (A-498. The in vivo activity was performed in female Swiss albino mice against Ehrlich Ascites Carcinoma (EAC. Among the synthesized compounds, o-iodoanilide, m-iodoanilide and p-iodoanilide derivatives of 2-(4-methyl benzene sulphonyl-pentanedioic acid amides showed encouraging activity in both the in vitro and in vivo compared to other compounds.

  2. In vitro anti-inflammatory and anticancer activities of extracts of Acalypha alopecuroidea (Euphorbiaceae)

    Czech Academy of Sciences Publication Activity Database

    Madlener, S.; Svačinová, Jana; Kitner, Miloslav; Kopecký, Jiří; Eytner, R.; Lackner, A.; Vo, T. P. N.; Frisch, R.; Grusch, M.; De Martin, R.; Doležal, Karel; Strnad, Miroslav; Krupitza, G.

    2009-01-01

    Roč. 35, č. 4 (2009), s. 881-891 ISSN 1019-6439 Institutional research plan: CEZ:AV0Z50380511; CEZ:AV0Z50200510 Keywords : Acalypha alopecuroidea * cancer * anti-inflammatory activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.447, year: 2009

  3. Synthesis, anticancer activity, and inhibition of tubulin polymerization by conformationally restricted analogues of lavendustin A.

    Science.gov (United States)

    Mu, Fanrong; Hamel, Ernest; Lee, Debbie J; Pryor, Donald E; Cushman, Mark

    2003-04-24

    Compounds in the lavendustin A series have been shown to inhibit both protein-tyrosine kinases (PTKs) and tubulin polymerization. Since certain lavendustin A derivatives can exist in conformations that resemble both the trans-stilbene structure of the PTK inhibitor piceatannol and the cis-stilbene structure of the tubulin polymerization inhibitor combretastatin A-4, the possibility exists that the ratio of the two types of activities of the lavendustins could be influenced through the synthesis of conformationally restricted analogues. Accordingly, the benzylaniline structure of a series of pharmacologically active lavendustin A fragments was replaced by either their cis- or their trans-stilbene relatives, and effects on both inhibition of tubulin polymerization and cytotoxicity in cancer cell cultures were monitored. Both dihydrostilbene and 1,2-diphenylalkyne congeners were also prepared and evaluated biologically. Surprisingly, conformational restriction of the bridge between the two aromatic rings of the lavendustins had no significant effect on biological activity. On the other hand, conversion of the three phenolic hydroxyl groups of the lavendustin A derivatives to their corresponding methyl ethers consistently abolished their ability to inhibit tubulin polymerization and usually decreased cytotoxicity in cancer cell cultures as well, indicating the importance of at least one of the phenolic hydroxyl groups. Further investigation suggested that the phenolic hydroxyl group in the salicylamide ring was required for activity, while the two phenol moieties in the hydroquinone ring could be methylated with retention of activity. Two of the lavendustin A derivatives displayed IC(50) values of 1.4 microM for inhibition of tubulin polymerization, which ranks them among the most potent of the known tubulin polymerization inhibitors.

  4. Involvement of Salicylic Acid on Antioxidant and Anticancer Properties, Anthocyanin Production and Chalcone Synthase Activity in Ginger (Zingiber officinale Roscoe Varieties

    Directory of Open Access Journals (Sweden)

    Ehsan Karimi

    2012-11-01

    Full Text Available The effect of foliar application of salicylic acid (SA at different concentrations (10−3 M and 10−5 M was investigated on the production of secondary metabolites (flavonoids, chalcone synthase (CHS activity, antioxidant activity and anticancer activity (against breast cancer cell lines MCF-7 and MDA-MB-231 in two varieties of Malaysian ginger, namely Halia Bentong and Halia Bara. The results of high performance liquid chromatography (HPLC analysis showed that application of SA induced the synthesis of anthocyanin and fisetin in both varieties. Anthocyanin and fisetin were not detected in the control plants. Accordingly, the concentrations of some flavonoids (rutin and apigenin decreased significantly in plants treated with different concentrations of SA. The present study showed that SA enhanced the chalcone synthase (CHS enzyme activity (involving flavonoid synthesis and recorded the highest activity value of 5.77 nkat /mg protein in Halia Bara with the 10−5 M SA treatment. As the SA concentration was decreased from 10−3 M to 10−5 M, the free radical scavenging power (FRAP increased about 23% in Halia Bentong and 10.6% in Halia Bara. At a concentration of 350 μg mL−1, the DPPH antioxidant activity recorded the highest value of 58.30%–72.90% with the 10−5 M SA treatment followed by the 10−3 M SA (52.14%–63.66% treatment. The lowest value was recorded in the untreated control plants (42.5%–46.7%. These results indicate that SA can act not only as an inducer but also as an inhibitor of secondary metabolites. Meanwhile, the highest anticancer activity against MCF-7 and MDA-MB-231 cell lines was observed for H. Bara extracts treated with 10−5 M SA with values of 61.53 and 59.88%, respectively. The results suggest that the high anticancer activity in these varieties may be related to the high concentration of potent anticancer components including fisetin and anthocyanin. The results thus indicate that the synthesis of

  5. Synthesis and anticancer activity of N-substituted 2-arylquinazolinones bearing trans-stilbene scaffold.

    Science.gov (United States)

    Mahdavi, Mohammad; Pedrood, Keyvan; Safavi, Maliheh; Saeedi, Mina; Pordeli, Mahboobeh; Ardestani, Sussan Kabudanian; Emami, Saeed; Adib, Mehdi; Foroumadi, Alireza; Shafiee, Abbas

    2015-05-05

    A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were designed, synthesized, and evaluated against human breast cancer cell lines including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl derivative 7h showed the best profile of activity (IC50 < 5 μM) against all cell lines, being 2-fold more potent than standard drug, etoposide. Our investigation revealed that the cytotoxic activity was significantly affected by N3-alkyl substituents. Furthermore, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that the prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Synthesis and Anticancer Activity of Di(3-thienylmethanol and Di(3-thienylmethane

    Directory of Open Access Journals (Sweden)

    Nagendra Kumar Kaushik

    2012-09-01

    Full Text Available Di(3-thienylmethanol (2 and di(3-thienylmethane (3 have been synthesized and screened against the T98G (brain cancer cell line. Treatment induced cell death (MTT and macro-colony assay, growth inhibition, cytogenetic damage (micronuclei formation, were studied as cellular response parameters. Treatment with the compounds enhanced growth inhibition and cell death in a concentration dependent manner in both T98G and HEK (normal cell lines. At higher concentrations (>20 µg/mL the cytotoxic effects of the compounds were highly significant. The effect on clonogenic capacity and micronuclei formation observed after treatment of cells. Amongst the compounds, compound 2 exhibited potent activity against T98G brain cancer cells. Despite potent in vitro activity, both compounds exhibited less cytotoxicity against normal human HEK cells at all effective concentrations.

  7. Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR

    Science.gov (United States)

    2012-01-01

    The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide. PMID:24900418

  8. Phytochemical screening, anti-oxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola).

    Science.gov (United States)

    Gavamukulya, Yahaya; Abou-Elella, Faten; Wamunyokoli, Fred; AEl-Shemy, Hany

    2014-09-01

    To determine the phytochemical composition, antioxidant and anticancer activities of ethanolic and water leaves extracts of Annona muricata (A. muricata) from the Eastern Uganda. Phytochemical screening was conducted using standard qualitative methods and a Chi-square goodness of fit test was used to assign the relative abundance of the different phytochemicals. The antioxidant activity was determined using the 2, 2-diphenyl-2-picrylhydrazyl and reducing power methods whereas the in vitro anticancer activity was determined using three different cell lines. Phytochemical screening of the extracts revealed that they were rich in secondary class metabolite compounds such as alkaloids, saponins, terpenoids, flavonoids, coumarins and lactones, anthraquinones, tannins, cardiac glycosides, phenols and phytosterols. Total phenolics in the water extract were (683.69±0.09) μg/mL gallic acid equivalents (GAE) while it was (372.92±0.15) μg/mL GAE in the ethanolic extract. The reducing power was 216.41 μg/mL in the water extract and 470.51 μg/mL GAE in the ethanolic extract. In vitro antioxidant activity IC50 was 2.0456 mg/mL and 0.9077 mg/mL for ethanolic and water leaves extracts of A. muricata respectively. The ethanolic leaves extract was found to be selectively cytotoxic in vitro to tumor cell lines (EACC, MDA and SKBR3) with IC50 values of 335.85 μg/mL, 248.77 μg/mL, 202.33 μg/mL respectively, while it had no cytotoxic effect on normal spleen cells. The data also showed that water leaves extract of A. muricata had no anticancer effect at all tested concentrations. The results showed that A. muricata was a promising new antioxidant and anticancer agent. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  9. Bioproduction and anticancer activity of biosurfactant produced by the dematiaceous fungus Exophiala dermatitidis SK80.

    Science.gov (United States)

    Chiewpattanakul, Paramaporn; Phonnok, Sirinet; Durand, Alain; Marie, Emmanuelle; Thanomsub, Benjamas Wongsatayanon

    2010-12-01

    A new biosurfactant producer was isolated from palm-oilcontaminated soil and later identified through morphology and DNA sequencing as the yeast-like fungus Exophiala dermatitidis. Biosurfactant production was catalyzed by vegetable oil, supplemented with a basal medium. The culture conditions that provided the biosurfactant with the highest surface activity were found to be 5% palm oil with 0.08% NH4NO3, at a pH of 5.3, with shaking at 200 rpm, and a temperature of 30 degrees C for a 14-day period of incubation. The biosurfactant was purified, in accordance with surfactant properties, by solvent fractionation using silica gel column chromatography. The chemical structure of the strongest surface-active compound was elucidated through the use of NMR and mass spectroscopy, and noted to be monoolein, which then went on to demonstrate antiproliferative activity against cervical cancer (HeLa) and leukemia (U937) cell lines in a dose-dependent manner. Interestingly, no cytotoxicity was observed with normal cells even when high concentrations were used. Cell and DNA morphological changes, in both cancer cell lines, were observed to be cell shrinkage, membrane blebbling, and DNA fragmentation.

  10. Exploring the Anticancer Activity of Grape Seed Extract on Skin Cancer Cell Lines A431

    Directory of Open Access Journals (Sweden)

    V. Mohansrinivasan

    2015-08-01

    Full Text Available In this study, grape seeds were extracted using ethyl acetate and petroleum ether by solvent-solvent extraction method. The phytochemical tests were performed to identify different phytochemical compounds present in the grape seed extract (GSE. Antibacterial activity of the GSE was determined using agar diffusion method against Gram- positive and Gram-negative bacteria. Gas chromatography-mass spectrometry (GC-MS and Fourier transform infrared spectroscopy (FTIR analysis was done to identify the presence of bioactive compounds and their functional groups. The GC-MS results revealed a total of four compounds, known to have potent activity against cancer cells, viz, squalene, the most potent compound found in ethyl acetate extract and diethyl phthalate, ethyl-9- cis -11- trans octadecadienoate and (R-(--14,-methyl-8-Hexadecyn-1-ol in petroleum ether extract. Cytotoxic activity of the GSE was observed against skin cancer cell lines A4321 using 3-(4, 5-dimethylthiazol-2-yl-2-5-diphenyl tetrazolium bromide MTT assay. The IC50 value of the GSE against A431 skin cancer cell line was 480 µg/mL. This is first such report against A4321 cell lines. The study gives the overall perception about importance of GSE in medicine and nutraceuticals purposes.

  11. Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition

    Science.gov (United States)

    Caffa, Irene; D'Agostino, Vito; Damonte, Patrizia; Soncini, Debora; Cea, Michele; Monacelli, Fiammetta; Odetti, Patrizio; Ballestrero, Alberto; Provenzani, Alessandro; Longo, Valter D.; Nencioni, Alessio

    2015-01-01

    Tyrosine kinase inhibitors (TKIs) are now the mainstay of treatment in many types of cancer. However, their benefit is frequently short-lived, mandating the search for safe potentiation strategies. Cycles of fasting enhance the activity of chemo-radiotherapy in preclinical cancer models and dietary approaches based on fasting are currently explored in clinical trials. Whether combining fasting with TKIs is going to be potentially beneficial remains unknown. Here we report that starvation conditions increase the ability of commonly administered TKIs, including erlotinib, gefitinib, lapatinib, crizotinib and regorafenib, to block cancer cell growth, to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway and to strengthen E2F-dependent transcription inhibition. In cancer xenografts models, both TKIs and cycles of fasting slowed tumor growth, but, when combined, these interventions were significantly more effective than either type of treatment alone. In conclusion, cycles of fasting or of specifically designed fasting-mimicking diets should be evaluated in clinical studies as a means to potentiate the activity of TKIs in clinical use. PMID:25909220

  12. Secondary metabolites constituents and antioxidant, anticancer and antibacterial activities of Etlingera elatior (Jack) R.M.Sm grown in different locations of Malaysia.

    Science.gov (United States)

    Ghasemzadeh, Ali; Jaafar, Hawa Z E; Rahmat, Asmah; Ashkani, Sadegh

    2015-09-23

    Etlingera elatior is a well-known herb in Malaysia with various pharmaceutical properties. E. elatior flowers grown in three different locations of Malaysia (Kelantan, Pahang and Johor), were investigated for differences in their content of secondary metabolites (total phenolics [TPC], total flavonoids [TFC], and total tannin content [TTC]) as well as for their antioxidant, anticancer, and antibacterial properties. Phenolic acids and flavonoids were isolated and identified using ultra-high performance liquid chromatography (UHPLC). Ferric reducing antioxidant potential (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used to evaluate the antioxidant activities. The anticancer activity of extracts was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. When extracted with various solvents (aqueous and ethanolic), samples from the different locations yielded significantly different results for TPC, TFC, and TTC as well as antioxidant activity. Aqueous extracts of E. elatior flowers collected from Kelantan exhibited the highest values: TPC (618.9 mg/100 g DM), TFC (354.2 mg/100 g DM), TTC (129.5 mg/100 g DM), DPPH (76.4 %), and FRAP (6.88 mM of Fe (II)/g) activity with a half-maximal inhibitory concentration (IC50) of 34.5 μg/mL compared with extracts of flowers collected from the other two locations. The most important phenolic compounds isolated in this study, based on concentration, were: gallic acid > caffeic acid > tannic acid > chlorogenic acid; and the most important flavonoids were: quercetin > apigenin > kaempferol > luteolin > myricetin. Extracts of flowers from Kelantan exhibited potent anticancer activity with a IC50of 173.1 and 196.2 μg/mL against the tumor cell lines MCF-7 and MDA-MB-231 respectively, compared with extracts from Pahang (IC50 = 204.5 and 246.2 μg/mL) and Johor samples (IC50 = 277.1 and 296.7 μg/mL). Extracts of E. elatior flowers also showed

  13. Piper betel leaf extract: anticancer benefits and bio-guided fractionation to identify active principles for prostate cancer management.

    Science.gov (United States)

    Paranjpe, Rutugandha; Gundala, Sushma R; Lakshminarayana, N; Sagwal, Arpana; Asif, Ghazia; Pandey, Anjali; Aneja, Ritu

    2013-07-01

    Plant extracts, a concoction of bioactive non-nutrient phytochemicals, have long served as the most significant source of new leads for anticancer drug development. Explored for their unique medicinal properties, the leaves of Piper betel, an evergreen perennial vine, are a reservoir of phenolics with antimutagenic, antitumor and antioxidant activities. Here, we show that oral feeding of betel leaf extract (BLE) significantly inhibited the growth of human prostate xenografts implanted in nude mice compared with vehicle-fed controls. To gain insights into the 'active principles', we performed a bioactivity-guided fractionation of methanolic BLE employing solvents of different polarity strengths using classical column chromatography. This approach yielded 15 fractions, which were then pooled to 10 using similar retention factors on thin-layer chromatographs. Bioactivity assays demonstrated that one fraction in particular, F2, displayed a 3-fold better in vitro efficacy to inhibit proliferation of prostate cancer cells than the parent BLE. The presence of phenols, hydroxychavicol (HC) and chavibetol (CHV), was confirmed in F2 by nuclear magnetic resonance, high-performance liquid chromatography and mass spectroscopy. Further, the HC containing F2 subfraction was found to be ~8-fold more potent than the F2 subfraction that contained CHV, in human prostate cancer PC-3 cells as evaluated by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. Removing CHV from F2 remarkably decreased the IC50 of this fraction, indicating that HC is perhaps the major bioactive constituent, which is present to an extent of 26.59% in BLE. These data provide evidence that HC is a potential candidate for prostate cancer management and warrants further preclinical evaluation.

  14. In vivo anticancer and immunomodulating activities of mannogalactoglucan-type polysaccharides from Lentinus edodes (Berkeley) Singer.

    Science.gov (United States)

    Jeff, Iteku Bekomo; Fan, Enxue; Tian, Meihong; Song, Chenyang; Yan, Jingmin; Zhou, Yifa

    2016-01-01

    There is considerable interest in the potential of mushrooms in modulating the immune system and/or suppressing tumor growth. Among the studied bioactive compounds in mushrooms, polysaccharides are the most important. Nontoxic fungal polysaccharides have a more important role in immunomodulating and antitumor activities which are related to their effects to act of immune effecter cells such as lymphocytes, macrophages, dendritic cells, and natural killer cells involved in the innate and adaptive immunity. Two mannogalactoglucan-type polysaccharides (WPLE-N-2 and WPLE-A0.5-2), purified from the fruiting bodies of Lentinus edodes, were evaluated for their effects on the cellular immune response of Sarcoma 180 (S-180)-bearing mice. Mice were treated with 100 mg/kg body weight of the polysaccharides for 10 days. Significant tumor regressions of the polysaccharide groups' mice were observed compared to the control group. These polysaccharides could induce an increase in nitrite oxide (NO) production in peritoneal macrophages, significantly increase macrophage phagocytosis of tumor-bearing mice and augment concanavalin (ConA) and lipopolysaccharide (LPS)-induced splenocytes proliferation. Our results indicated that immunomodulating activity occurred through host mediation in response to lymphocyte proliferation, macrophage phagocytosis and induction of NO production while the antitumor activity occurred through direct cytotoxicity. Our findings suggest that mannogalactoglucan-type polysaccharides from L. edodes can be explored as novel potential immunostimulants. Our research provides essential data to a better understanding of L. edodes bioactive compounds, especially polysaccharides. Our results also confirm the key role of β-linkages in the antitumor and immunomodulating effects of polysaccharides.

  15. Green synthesis of silver nanoparticles from aqueous leaf extract of Pomegranate (Punica granatum) and their anticancer activity on human cervical cancer cells

    Science.gov (United States)

    Sarkar, Sonia; Kotteeswaran, Venkatesan

    2018-06-01

    Plants contain different important phytochemicals that can be used as a potential treatment for various ailments including cancer. The green synthesis of silver nanoparticles from the extract of different plant parts has gained a wide range of engrossment among the researchers due to its unique optical and structural property. The aim of this study is green synthesis of silver nanoparticles from the aqueous leaf extract of pomegranate (Punica granatum) and to investigate its anticancer activity on human cervical cancer cells (HeLa). The synthesis of silver nanoparticle was depicted by the colour change from golden yellowish to dark brownish, UV-visible spectral analysis gave a characteristic surface plasmon absorption peak at . Further morphological characterization was done by Zeta potential where the size analysis was depicted to be 46.1 nm and zeta potential as . Fourier transform infrared spectroscopy (FTIR) inferred 3 intense sharp peaks at , , , confirmed the presence of flavonoids and polyphenols. The scanning electron microscopy (SEM) analysis with energy diffraction spectroscopy (EDS) confirmed the presence of silver nanoparticles with size ranged from to . X-ray diffraction (XRD) confirmed the crystallographic nature of silver. The cell proliferation activity of nanoparticles was tested by 3, ‑4, 5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) assay where the inhibitory concentration () was found at inhibiting of HeLa cell line. The anticancer activity of nanoparticles was determined by lactate dehydrogenase (LDH) assay where showed of cytotoxicity. Furthermore, the anticancer property of nanoparticles was confirmed by the DNA fragmentation assay.

  16. Synthesis and Anticancer Activities of Novel 1,4-Disubstituted Phthalazines

    Directory of Open Access Journals (Sweden)

    Ping Gong

    2006-07-01

    Full Text Available A series of novel 1-anilino-4-(arylsulfanylmethylphthalazines were designed and synthesized. The structures of all the compounds were confirmed by IR, 1H-NMR, elemental analysis and MS. The analogues 1-(3-chloro-4-fluoroanilino-4-(3,4- difluorophenylthio-methylphthalazine (12 and 1-(4-fluoro-3-trifluoromethylanilino-4- (3,4-difluorophenyl-thiomethylphthalazine (13 showed higher activity than a cisplatin control when tested in vitro against two different cancer cell lines using the microculture tetrazolium method (MTT method.

  17. The Impact of the Roast Levels of Coffee Extracts on their Potential Anticancer Activities.

    Science.gov (United States)

    Mojica, Benigno E; Fong, Lisa E; Biju, Denny; Muharram, Alfeah; Davis, Isabel M; Vela, Klarisse O; Rios, Diana; Osorio-Camacena, Elena; Kaur, Baljit; Rojas, Sebastian M; Forester, Sarah C

    2018-04-01

    Coffee is one of the most widely consumed beverages in the world and contains numerous phytochemicals that are beneficial to consumer health. The phytochemical profile of coffee, however, can be affected by the roast level. In this study, we compared the effect of roasting level on the growth inhibitory activity of HT-29 (colon) and SCC-25 (oral) cancer cell lines. The different roasting stages selected for this study were green, cinnamon/blonde, city/medium, full city/medium-dark, and full city plus/dark. Cancer cells were treated with various concentrations of coffee extracts for 72 hr. Cell viability was quantified using the thiazolyl blue tetrazolium bromide assay. It was found that the lighter roast extracts, Cinnamon in particular, reduced cell growth more than darker roast extracts. The Cinnamon extract had the greatest amount of total phenolic content and antioxidant activity. Relative levels of gallic, caffeic, and chlorogenic acid in the extracts were also compared. The Cinnamon coffee extract had the highest levels of gallic and caffeic acids, which have both been widely-regarded as bioactive phytochemicals. In conclusion, the consumption of lighter roasted coffee, may contribute to the prevention of certain types of cancer such as oral and colon. Chemical compounds in coffee may reduce the risk for certain types of cancers. These compounds may be particularly abundant in lighter roasted coffee. Therefore, lighter roasted coffee could contribute to the prevention of cancer through a healthy diet. © 2018 Institute of Food Technologists®.

  18. Antimicrobial and anticancer activity of AgNPs coated with Alphonsea sclerocarpa extract.

    Science.gov (United States)

    Doddapaneni, Suman Joshi D S; Amgoth, Chander; Kalle, Arunasree M; Suryadevara, Surya Narayana; Alapati, Krishna Satya

    2018-03-01

    The synthesis and characterization of an aggregate of AgNPs coated with plant extract (PE) from Alphonsea sclerocarpa and its significant antimicrobial activity and inhibition on K562 (blood cancer) cells have been appended in the article. Synthesis of aggregate [(AgNPs)-(PE)] has been followed by a facile eco-friendly approach without using any harmful chemicals. The morphology of an aggregate [(AgNPs)-(PE)] was confirmed by TEM and SEM microscopic characterizations. Properties like solid state, the presence of functional groups, and elemental composition have been characterized through the XRD, FTIR, and EDAX. The biocompatibility of synthesized aggregate of [(AgNPs)-(PE)] was confirmed by the MTT assay. An in vitro cell (HEK293)-based studies were performed for the biocompatibility tests and it is found that the aggregate [(AgNPs)-(PE)] is not harmful to normal/healthy cells. Even though A. sclerocarpa show the antimicrobial (antibacterial and antifungal) activity, it has been further enhanced with the developed aggregate of [(AgNPs)-(PE)]. Furthermore, it has been extended to examine the cellular inhibition on K562 cells and obtained > 75% cell inhibition for 24 h treated cells.

  19. Furano diterpenes from Pterodon pubescens Benth with selective in vitro anticancer activity for prostate cell line

    International Nuclear Information System (INIS)

    Spindola, Humberto M.; Carvalho, Joao E. de; Ruiz, Ana Lucia T.G.; Rodrigues, Rodney A. F.; Denny, Carina; Sousa, Ilza M. de Oliveira; Foglio, Mary Ann; Tamashiro, Jorge Y.

    2009-01-01

    Activity guided fractionation of Pterodon pubescens Benth. methylene chloride-soluble fraction afforded novel 6α-acetoxi 7β-hydroxy-vouacapan 1 and four known diterpene furans 2, 3, 4, 5. The compounds were evaluated for in vitro cytotoxic activities against human normal cells and tumour cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-H460 (lung, non-small cells), OVCAR-03 (ovarian), PC-3 (prostate), HT-29 (colon), 786-0 (renal), K562 (leukemia) and NCI-ADR/RES (ovarian expressing phenotype multiple drugs resistance). Results were expressed by three concentration dependent parameters GI 50 (concentration that produces 50% growth inhibition), TGI (concentration that produces total growth inhibition or cytostatic effect) and LC 50 (concentration that produces .50% growth, a cytotoxicity parameter). Also, in vitro cytotoxicity was evaluated against 3T3 cell line (mouse embryonic fibroblasts). Antiproliferative properties of compounds 1, 4 and 5 are herein reported for the first time. These compounds showed selectivity in a concentration-dependent way against human PC-3. Compound 1 demonstrated selectivity 26 fold more potent than the positive control, doxorubicin, for PC-3 (prostrate) cell line based on GI 50 values, causing cytostatic effect (TGI value) at a concentration fifteen times less than positive control. Moreover comparison of 50% lethal concentration (LC 50 value) with positive control (doxorubicin) suggested that compound 1 was less toxic. (author)

  20. The in Vitro Structure-Related Anti-Cancer Activity of Ginsenosides and Their Derivatives

    Directory of Open Access Journals (Sweden)

    Liang Liu

    2011-12-01

    Full Text Available Panax ginseng has long been used in Asia as a herbal medicine for the prevention and treatment of various diseases, including cancer. The current study evaluated the cytotoxic potency against a variety of cancer cells by using ginseng ethanol extracts (RSE, protopanaxadiol (PPD-type, protopanaxatriol (PPT-type ginsenosides fractions, and their hydrolysates, which were prepared by stepwise hydrolysis of the sugar moieties of the ginsenosides. The results showed that the cytotoxic potency of the hydrolysates of RSE and total PPD-type or PPT-type ginsenoside fractions was much stronger than the original RSE and ginsenosides; especially the hydrolysate of PPD-type ginsenoside fractions. Subsequently, two derivatives of protopanaxadiol (1, compounds 2 and 3, were synthesized via hydrogenation and dehydration reactions of compound 1. Using those two derivatives and the original ginsenosides, a comparative study on various cancer cell lines was conducted; the results demonstrated that the cytotoxic potency was generally in the descending order of compound 3 > 20(S-dihydroprotopanaxadiol (2 > PPD (1 > 20(S-Rh2 > 20(R-Rh2 ≈ 20(R-Rg3 ≈ 20(S-Rg3. The results clearly indicate the structure-related activities in which the compound with less polar chemical structures possesses higher cytotoxic activity towards cancer cells.

  1. Antioxidant and anticancer activities of Chenopodium quinoa leaves extracts - in vitro study.

    Science.gov (United States)

    Gawlik-Dziki, Urszula; Świeca, Michał; Sułkowski, Maciej; Dziki, Dariusz; Baraniak, Barbara; Czyż, Jarosław

    2013-07-01

    The nutraceutical potential of Chenopodium quinoa Leaves (ChL) was assessed through analyses of their phenolic content, elucidation of the effect of ChL phenolic compounds on cancer cell properties and estimation of their antioxidative activity, bioaccessibility and bioavailability in vitro. Considerable amounts of ferulic, sinapinic and gallic acids, kaempferol, isorhamnetin and rutin were observed in the chemical ChL extract and were linked with its inhibitory effect on prostate cancer cell proliferation, motility and cellular competence for gap junctional communication. Both extracts, chemical and obtained after simulated digestion, exerted an inhibitory effect on lipoxygenase activity, paralleled by their considerable chelating, antioxidative, antiradical and reducing power. These observations indicate that phenolic ChL compounds may exert a chemopreventive and anticarcinogenic effect on oxidative stress and ROS-dependent intracellular signaling via synergic effects. The relatively high potential bioaccessibility and bioavailability of the compounds probably responsible for these effects demonstrates the suitability of ChL for dietary supplementation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. CoFactor: Folate Requirement for Optimization of 5-Fluouracil Activity in Anticancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2010-01-01

    Full Text Available Intracellular reduced folate exists as a “pool” of more than 6 interconvertable forms. One of these forms, 5,10 methylenetetrahydrofolic acid (CH2THF, is the key one-carbon donor and reduced folate substrate for thymidylate synthase (TS. This pathway has been an important target for chemotherapy as it provides one of the necessary nucleotide substrates for DNA synthesis. The fluoropyrimidine 5-fluorouracil (5-FU exerts its main cytotoxic activity through TS inhibition. Leucovorin (5-formyltetrahydrofolate; LV has been used to increase the intracellular reduced folate pools and enhance TS inhibition. However, it must be metabolized within the cell through multiple intracellular enzymatic steps to form CH2THF. CoFactor (USAN fotrexorin calcium, (dl-5,10,-methylenepteroyl-monoglutamate calcium salt is a reduced folate that potentiates 5-FU cytotoxicity. According to early clinical trials, when 5-FU is modulated by CoFactor instead of LV, there is greater anti-tumor activity and less toxicity. This review presents the emerging role of CoFactor in colorectal and nongastrointestinal malignancies.

  3. Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Temilolu Idowu

    2017-11-01

    Full Text Available Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV, leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds.

  4. Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex.

    Science.gov (United States)

    Biscaro, Fernanda; Parisotto, Eduardo Benedetti; Zanette, Vanilde Citadini; Günther, Tania Mara Fischer; Ferreira, Eduardo Antonio; Gris, Eliana Fortes; Correia, João Francisco Gomes; Pich, Claus Tröger; Mattivi, Fulvio; Filho, Danilo Wilhelm; Pedrosa, Rozangela Curi

    2013-06-01

    Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil, where it is commonly known as "Sangue-de-Dragão". Its red latex is used traditionally for treating ulcers, diabetes and cancer. To evaluate antitumor activities of Croton celtififolius latex in vitro and in vivo. Phytochemical analyses were conducted using HPLC-DAD-MS. Cytotoxic, nuclease and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay and ethidium bromide (EB)/acridine orange methods, respectively, and antitumor activity was determined in the Ehrlich ascites carcinoma (EAC) mouse model. Phytochemical studies indicated a high phenol content of flavonols (45.67 ± 0.24 and 18.01 ± 0.23 mg/mL of myricetin and quercetin, respectively) and flavan-3-ols (114.12 ± 1.84 and 1527.41 ± 16.42 mg/L of epicatechin and epigallocatechin, respectively) in latex. These compounds reduced MCF-7 and EAC cell viability in the MTT assay (IC50 = 169.0 ± 1.8 and 187.0 ± 2.2 μg/mL, respectively). Latex compounds caused significant DNA fragmentation and increased the number of apoptotic cells (negative control (NC), 12%; latex, 41%) as indicated by differential staining in the EB/acridine orange assay. The in vivo latex treatment at 3.12 mg/kg/day reduced the body weight by 7.57 ± 2.04 g and increased median survival time to 17.5 days when compared to the NC group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%. These results agree with ethno-pharmacological reports showing cytotoxicity and antitumor activity of C. celtidifolius latex. The mechanism of antitumor action may be related to direct DNA fragmentation that reduces survival and induces apoptosis.

  5. Novel concepts and strategies in anticancer metallodrug development : towards oral activity, peptide conjugation and mass spectrometric applications

    Energy Technology Data Exchange (ETDEWEB)

    Meier, S.

    2013-07-01

    Some ruthenium and osmium complexes are promising anticancer drug candidates and the preparation of organometallic RuII and OsII complexes, stabilized by a η6-coordinating arene, represents the latest strategy for obtaining anticancer active metallodrugs with an intriguing activity profile. This PhD thesis reports on the discovery of novel tumour-inhibiting RuII– and OsII–arene metallodrugs and on studies aimed at understanding the molecular interactions of established anticancer agents and drug candidates with biomolecules. Although this field of research is intensely investigated, S,N-bidentate ligand-containing RuII and OsII metallodrugs are reported for the first time. The ligands are based on 2-pyridinecarbothioamides, which show activity as gastric mucosal protectants and are largely non-toxic in vivo (J. Med. Chem., 1990, 33, 327–336). Complexation to the organometallic moiety, however, yields highly cytotoxic metallodrugs in the chemoresistant colon carcinoma and multidrug-resistant non-small lung cancer cell lines. Their aqueous behaviour and drug-likeness properties suggest that this novel family of organometallic anticancer agents may be suitable for oral administration. Additionally, studies with the nucleosome core particle showed that these metallodrugs bind exclusively to the histone proteins at histone dimer–dimer and dimer–tetramer interfaces and therefore, may interfere with chromatin dynamics as a possible mode of action. Organometallic RuII–arene metallodrugs based on O,O-bidentate pyronato ligands typically show low antiproliferative activity. Intriguingly, triazolyl-modified pyrones coordinated to RuII–p-cymene yield highly cytotoxic agents in vitro. The strategy of triazolyl modification was followed to prepare the first organometallic Ru–peptide bioconjugate with cytotoxic activity in the low micromolar range in an ovarian cancer cell line. The metal–peptide bioconjugate was thoroughly characterized by different methods

  6. Synthesis, characterization and anticancer activities of two lanthanide(III) complexes with a nicotinohydrazone ligand

    Science.gov (United States)

    Xu, Zhou-Qin; Mao, Xian-Jie; Jia, Lei; Xu, Jun; Zhu, Tao-Feng; Cai, Hong-Xin; Bie, Hong-Yan; Chen, Ru-Hua; Ma, Tie-liang

    2015-12-01

    Two isostructural acylhydrazone based complexes, namely [Ce(penh)2(H2O)4](NO3)3·4H2O (1) and [Sm(penh)2(NO3)2](NO3)·C2H5OH (2) (penh = 2-acetylpyridine nicotinohydrazone), have been obtained and characterized by physico-chemical and spectroscopic methods. The ten-coordinated lanthanide metal ion in each complex is surrounded by two independent tridentate neutral acylhydrazones with two ON2 donor sets. The other four coordination oxygen atoms are from four water molecules and two bidentate nitrate anions for complexes 1 and 2, respectively, thus giving distorted bicapped square antiprism geometry. Both complexes have excellent antitumor activity towards human pancreatic cancer (PATU8988), human colorectal cancer (lovo) and human gastric cancer(SGC7901) cell line. Furthermore, the cell apoptosis of complex 1 is detected by AnnexinV/PI flow cytometry.

  7. In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets.

    Science.gov (United States)

    Bezagu, Marine; Clarhaut, Jonathan; Renoux, Brigitte; Monti, Fabrice; Tanter, Mickael; Tabeling, Patrick; Cossy, Janine; Couture, Olivier; Papot, Sebastien; Arseniyadis, Stellios

    2017-12-15

    The efficiency of a drug is usually highly dependent on the way it is administered or delivered. As such, targeted-therapy, which requires conceiving drug-delivery vehicles that will change their state from a relatively stable structure with a very slow leak-rate to an unstable structure with a fast release, clearly improves the pharmacokinetics, the absorption, the distribution, the metabolism and the therapeutic index of a given drug. In this context, we have developed a particularly effective double stimuli-responsive drug-delivery method allowing an ultrasound-induced release of a monomethylauristatin E-glucuronide prodrug and its subsequent activation by a β-glucuronidase. This led to an increase of cytotoxicity of about 80% on cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. In Vitro Anticancer Activity and Structural Characterization of Ubiquinones from Antrodia cinnamomea Mycelium

    Directory of Open Access Journals (Sweden)

    I-Chuan Yen

    2017-05-01

    Full Text Available Two new ubiquinones, named antrocinnamone and 4-acetylantrocamol LT3, were isolated along with six known ubiquinones from Antrodia cinnamomea (Polyporaceae mycelium. The developed HPLC analysis methods successfully identified eight different ubiquinones, two benzenoids, and one maleic acid derivative from A. cinnamomea. The ubiquinones 1–8 exhibited potential and selective cytotoxic activity against three human cancer cell lines, with IC50 values ranging from 0.001 to 35.883 μM. We suggest that the different cytotoxicity levels were related to their chemical structures, especially the 4-hydroxycyclohex-2-enone ring and the presence of a free hydroxyl group in the side chain. The suppression by 4-acetylantrocamol LT3 stopped the cell cycle at the beginning of the G2-M phase thus making the cell cycle arrest at the sub-G1 phase as compared with control cells.

  9. Anticancer Activity of Polyoxometalate-Bisphosphonate Complexes: Synthesis, Characterization, In Vitro and In Vivo Results.

    Science.gov (United States)

    Boulmier, Amandine; Feng, Xinxin; Oms, Olivier; Mialane, Pierre; Rivière, Eric; Shin, Christopher J; Yao, Jiaqi; Kubo, Tadahiko; Furuta, Taisuke; Oldfield, Eric; Dolbecq, Anne

    2017-07-03

    We synthesized a series of polyoxometalate-bisphosphonate complexes containing Mo VI O 6 octahedra, zoledronate, or an N-alkyl (n-C 6 or n-C 8 ) zoledronate analogue, and in two cases, Mn as a heterometal. Mo 6 L 2 (L = Zol, ZolC 6 , ZolC 8 ) and Mo 4 L 2 Mn (L = Zol, ZolC 8 ) were characterized by using single-crystal X-ray crystallography and/or IR spectroscopy, elemental and energy dispersive X-ray analysis and 31 P NMR. We found promising activity against human nonsmall cell lung cancer (NCI-H460) cells with IC 50 values for growth inhibition of ∼5 μM per bisphosphonate ligand. The effects of bisphosphonate complexation on IC 50 decreased with increasing bisphosphonate chain length: C 0 ≈ 6.1×, C 6 ≈ 3.4×, and C 8 ≈ 1.1×. We then determined the activity of one of the most potent compounds in the series, Mo 4 Zol 2 Mn(III), against SK-ES-1 sarcoma cells in a mouse xenograft system finding a ∼5× decrease in tumor volume than found with the parent compound zoledronate at the same compound dosing (5 μg/mouse). Overall, the results are of interest since we show for the first time that heteropolyoxomolybdate-bisphosphonate hybrids kill tumor cells in vitro and significantly decrease tumor growth, in vivo, opening up new possibilities for targeting both Ras as well as epidermal growth factor receptor driven cancers.

  10. Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation.

    Directory of Open Access Journals (Sweden)

    Xinbing Sui

    Full Text Available Colorectal cancer (CRC is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation.

  11. Evaluation of Bioactive Compounds, Pharmaceutical Quality, and Anticancer Activity of Curry Leaf (Murraya koenigii L.

    Directory of Open Access Journals (Sweden)

    Ali Ghasemzadeh

    2014-01-01

    Full Text Available In this study, we investigated some bioactive compounds and pharmaceutical qualities of curry leaf (Murraya koenigii L. extracts from three different locations in Malaysia. The highest TF and total phenolic (TP contents were observed in the extracts from Kelantan (3.771 and 14.371 mg/g DW, followed by Selangor (3.146 and 12.272 mg/g DW and Johor (2.801 and 12.02 mg/g DW, respectively. High quercetin (0.350 mg/g DW, catechin (0.325 mg/g DW, epicatechin (0.678 mg/g DW, naringin (0.203 mg/g DW, and myricetin (0.703 mg/g DW levels were observed in the extracts from Kelantan, while the highest rutin content (0.082 mg/g DW was detected in the leaves from Selangor. The curry leaf extract from Kelantan exhibited higher concentration of gallic acid (0.933 mg/g DW than that from Selangor (0.904 mg/g DW and Johor (0.813 mg/g DW. Among the studied samples, the ones from Kelantan exhibited the highest radical scavenging activity (DPPH, 66.41% and ferric reduction activity potential (FRAP, 644.25 μm of Fe(II/g followed by those from Selangor (60.237% and 598.37 μm of Fe(II/g and Johor (50.76% and 563.42 μm of Fe(II/g, respectively. A preliminary screening showed that the curry leaf extracts from all the locations exhibited significant anticarcinogenic effects inhibiting the growth of breast cancer cell line (MDA-MB-231 and maximum inhibition of MDA-MB-231 cell was observed with the curry leaf extract from Kelantan. Based on these results, it is concluded that Malaysian curry leaf collected from the North (Kelantan might be potential source of potent natural antioxidant and beneficial chemopreventive agents.

  12. Evaluation of Bioactive Compounds, Pharmaceutical Quality, and Anticancer Activity of Curry Leaf (Murraya koenigii L.)

    Science.gov (United States)

    Ghasemzadeh, Ali; Jaafar, Hawa Z. E.; Rahmat, Asmah; Devarajan, Thiyagu

    2014-01-01

    In this study, we investigated some bioactive compounds and pharmaceutical qualities of curry leaf (Murraya koenigii L.) extracts from three different locations in Malaysia. The highest TF and total phenolic (TP) contents were observed in the extracts from Kelantan (3.771 and 14.371 mg/g DW), followed by Selangor (3.146 and 12.272 mg/g DW) and Johor (2.801 and 12.02 mg/g DW), respectively. High quercetin (0.350 mg/g DW), catechin (0.325 mg/g DW), epicatechin (0.678 mg/g DW), naringin (0.203 mg/g DW), and myricetin (0.703 mg/g DW) levels were observed in the extracts from Kelantan, while the highest rutin content (0.082 mg/g DW) was detected in the leaves from Selangor. The curry leaf extract from Kelantan exhibited higher concentration of gallic acid (0.933 mg/g DW) than that from Selangor (0.904 mg/g DW) and Johor (0.813 mg/g DW). Among the studied samples, the ones from Kelantan exhibited the highest radical scavenging activity (DPPH, 66.41%) and ferric reduction activity potential (FRAP, 644.25 μm of Fe(II)/g) followed by those from Selangor (60.237% and 598.37 μm of Fe(II)/g) and Johor (50.76% and 563.42 μm of Fe(II)/g), respectively. A preliminary screening showed that the curry leaf extracts from all the locations exhibited significant anticarcinogenic effects inhibiting the growth of breast cancer cell line (MDA-MB-231) and maximum inhibition of MDA-MB-231 cell was observed with the curry leaf extract from Kelantan. Based on these results, it is concluded that Malaysian curry leaf collected from the North (Kelantan) might be potential source of potent natural antioxidant and beneficial chemopreventive agents. PMID:24693327

  13. Evaluation of Bioactive Compounds, Pharmaceutical Quality, and Anticancer Activity of Curry Leaf (Murraya koenigii L.).

    Science.gov (United States)

    Ghasemzadeh, Ali; Jaafar, Hawa Z E; Rahmat, Asmah; Devarajan, Thiyagu

    2014-01-01

    In this study, we investigated some bioactive compounds and pharmaceutical qualities of curry leaf (Murraya koenigii L.) extracts from three different locations in Malaysia. The highest TF and total phenolic (TP) contents were observed in the extracts from Kelantan (3.771 and 14.371 mg/g DW), followed by Selangor (3.146 and 12.272 mg/g DW) and Johor (2.801 and 12.02 mg/g DW), respectively. High quercetin (0.350 mg/g DW), catechin (0.325 mg/g DW), epicatechin (0.678 mg/g DW), naringin (0.203 mg/g DW), and myricetin (0.703 mg/g DW) levels were observed in the extracts from Kelantan, while the highest rutin content (0.082 mg/g DW) was detected in the leaves from Selangor. The curry leaf extract from Kelantan exhibited higher concentration of gallic acid (0.933 mg/g DW) than that from Selangor (0.904 mg/g DW) and Johor (0.813 mg/g DW). Among the studied samples, the ones from Kelantan exhibited the highest radical scavenging activity (DPPH, 66.41%) and ferric reduction activity potential (FRAP, 644.25  μ m of Fe(II)/g) followed by those from Selangor (60.237% and 598.37  μ m of Fe(II)/g) and Johor (50.76% and 563.42  μ m of Fe(II)/g), respectively. A preliminary screening showed that the curry leaf extracts from all the locations exhibited significant anticarcinogenic effects inhibiting the growth of breast cancer cell line (MDA-MB-231) and maximum inhibition of MDA-MB-231 cell was observed with the curry leaf extract from Kelantan. Based on these results, it is concluded that Malaysian curry leaf collected from the North (Kelantan) might be potential source of potent natural antioxidant and beneficial chemopreventive agents.

  14. Discovery of new A- and B-type laxaphycins with synergistic anticancer activity.

    Science.gov (United States)

    Cai, Weijing; Matthew, Susan; Chen, Qi-Yin; Paul, Valerie J; Luesch, Hendrik

    2018-05-15

    Two new cyclic lipopeptides termed laxaphycins B4 (1) and A2 (2) were discovered from a collection of the marine cyanobacterium Hormothamnion enteromorphoides, along with the known compound laxaphycin A. The planar structures were solved based on a combined interpretation of 1D and 2D NMR data and mass spectral data. The absolute configurations of the subunits were determined by chiral LC-MS analysis of the hydrolysates, advanced Marfey's analysis and 1D and 2D ROESY experiments. Consistent with similar findings on other laxaphycin A- and B-type peptides, laxaphycin B4 (1) showed antiproliferative effects against human colon cancer HCT116 cells with IC 50 of 1.7 µM, while laxaphycins A and A2 (2) exhibited weak activities. The two major compounds isolated from the sample, laxaphycins A and B4, were shown to act synergistically to inhibit the growth of HCT116 colorectal cancer cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Preparation and Evaluation anticancer activity of D-glucosamine Nanoparticles on Metastatic cancer Model in vivo

    Directory of Open Access Journals (Sweden)

    Neda Soleimani

    2016-07-01

    Full Text Available Objective(s: Breast cancer imposes a highest rate of malignancy among the women all around the world. Chitin and its derivatives such as D-glucosamine-carboxymethyl chitin and Di-hydroxy propyl chitin have immune-modulating effects and influence on innate and acquisitive immunity which lead to cell activity enhancement. The aim of this study was investigating the effect of D-glucosamine nanoparticle on immune responses such as the changes in cytokines type 1 and 2 level in tumoral mice. Methods: Nanoparticles were synthesized by ionic gelation method and characterized by DLS and SEM methods. Tumors were induced in experimental mice and subsequently treated with nanoparticles. Then, the production of cytokine interferon-γ (IFN-γ and interleukin 4 (IL-4 were evaluated. Results: The obtained results showed a significant increase in the level of IFN-γ production in the mice group treated with nanoparticles compared to control groups. Additionally, there was a reduction in the level of IL-4 and tumor size in the test group. Conclusions: D-glucosamine nanoparticles can be proposed as a stimulator of the immune system and a promising compound for cancer treatment in the future.

  16. Antioxidant and anticancer activities of Plectranthus stocksii Hook. f. leaf and stem extracts

    Directory of Open Access Journals (Sweden)

    Kasipandi Muniyandi

    2017-04-01

    Full Text Available The properties of Plectranthus stocksii—a well-known folk medicinal plant—were investigated. The plant extracts were successively extracted and tested for phytochemicals using high performance liquid chromatography, while antioxidant and anticancerous properties were assessed using MCF-7, Caco-2 and RAW 264.7 cancerous cell line models. The methanolic extract of leaves showed higher concentrations of total phenolics (415.41 mg gallic acid equivalents/g extract and tannins (177.53 mg gallic acid equivalents/g extract contents than other studied extracts. In the case of flavonoids, ethyl acetate extract of leaf (LEA showed a higher concentration (777.11 mg rutin equivalents/g extract and was also found to have better antioxidant activity against stable radical 2,2-diphenylpicrylhydrazyl (3.46 μg/mL, 2,2′azinobis (3-ethylbenzothiozoline-6-sulfonic acid disodium salt radical (27.41 mM Trolox equivalent/g extract and superoxide (24.16 μg/mL radicals and showed better IC50 (the concentration of the sample at which the inhibition rate reaches 50% values on MCF-7 (48.874 μg/mL and Caco-2 (36.088 μg/mL cancerous cell line models. The immense anti-oxidant potential of P. stocksii leaf and stem extracts could be utilized as a good source of natural, anti-oxidant supplement in food to defend against oxidative-stress-related disorders and more generally in the food safety industry.

  17. Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles.

    Science.gov (United States)

    Mady, Fatma M; Shaker, Mohamed A

    2017-01-01

    Despite the fact that various studies have investigated the clinical relevance of ellagic acid (EA) as a naturally existing bioactive substance in cancer therapy, little has been reported regarding the efficient strategy for improving its oral bioavailability. In this study, we report the formulation of EA-loaded nanoparticles (EA-NPs) to find a way to enhance its bioactivity as well as bioavailability after oral administration. Poly(ε-caprolactone) (PCL) was selected as the biodegradable polymer for the formulation of EA-NPs through the emulsion-diffusion-evaporation technique. The obtained NPs have been characterized by measuring particle size, zeta potential, Fourier transform infrared, differential scanning calorimetry, and X-ray diffraction. The entrapment efficiency and the release profile of EA was also determined. In vitro cellular uptake and cytotoxicity of the obtained NPs were evaluated using Caco-2 and HCT-116 cell lines, respectively. Moreover, in vivo study has been performed to measure the oral bioavailability of EA-NPs compared to free EA, using New Zealand white rabbits. NPs with distinct shape were obtained with high entrapment and loading efficiencies. Diffusion-driven release profile of EA from the prepared NPs was determined. EA-NP-treated HCT-116 cells showed relatively lower cell viability compared to free EA-treated cells. Fluorometric imaging revealed the cellular uptake and efficient localization of EA-NPs in the nuclear region of Caco-2 cells. In vivo testing revealed that the oral administration of EA-NPs produced a 3.6 times increase in the area under the curve compared to that of EA. From these results, it can be concluded that incorporation of EA into PCL as NPs enhances its oral bioavailability and activity.

  18. Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model.

    Science.gov (United States)

    Sittaramane, Vinoth; Padgett, Jihan; Salter, Philip; Williams, Ashley; Luke, Shauntelle; McCall, Rebecca; Arambula, Jonathan F; Graves, Vincent B; Blocker, Mark; Van Leuven, David; Bowe, Keturah; Heimberger, Julia; Cade, Hannah C; Immaneni, Supriya; Shaikh, Abid

    2015-11-01

    In this study the rational design, synthesis, and anticancer activity of quinoline-derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp(3) -C-H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4-trifluoro-3-hydroxy-3-(quinolin-2-ylmethyl)butanoate (1), 2-benzyl-1,1,1-trifluoro-3-(quinolin-2-yl)propan-2-ol (2), and trifluoro-3-(isoquinolin-1-yl)-2-(thiophen-2-yl)propan-2-ol (3). Compounds 2 and 3 were found to be more toxic than compound 1; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2, with an LC50 value of 14.14 μm, has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells.

    Science.gov (United States)

    Gu, Mancang; Nishihara, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan A; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey A; Wolpin, Brian M; Giannakis, Marios; Aguirre, Andrew J; Bass, Adam J; Drew, David A; Chan, Andrew T; Fuchs, Charles S; Qian, Zhi Rong; Ogino, Shuji

    2017-10-20

    Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA -mutant colorectal carcinoma, but not in PIK3CA -wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA -mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA -mutant colon cancer cells than for PIK3CA -wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA -mutant and six PIK3CA -wild-type human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A>G (p.H1047R) or c.1633G>A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA -mutant cells than in PIK3CA -wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA -mutant cells than in PIK3CA -wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A>G (p.H1047R) or c.1633G>A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA -mutated colon cancer cells than in PIK3CA -wild-type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA -mutant colon cancer.

  20. Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Mady FM

    2017-10-01

    . From these results, it can be concluded that incorporation of EA into PCL as NPs enhances its oral bioavailability and activity. Keywords: nanoparticles, ellagic acid, poly(ε-caprolactone, bioavailability, cytotoxicity, oral administration

  1. Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A role played by the lactone moiety.

    Science.gov (United States)

    Qiu, Haibo; Qian, Shan; Head, Sarah A; Liu, Jun O; Jin, Zhendong

    2016-10-01

    Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, a new analog ZJ-109 was designed and synthesized to probe the importance of the lactone moiety of the molecule by replacing the lactone in ZJ-101 with a lactam. The biological evaluation showed that ZJ-109 is about 8-12 times less active against cancer cells in vitro than ZJ-101, suggesting that the lactone moiety of the molecule is important for its anticancer activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Evaluation of traditionally used medicinal plants for anticancer, antioxidant, anti-inflammatory and anti-viral (HPV-1) activity

    Czech Academy of Sciences Publication Activity Database

    Twilley, D.; Langhansová, Lenka; Palaniswamy, D.; Lall, N.

    2017-01-01

    Roč. 112, SEP (2017), s. 494-500 ISSN 0254-6299 Institutional support: RVO:61389030 Keywords : Anticancer * cox-2 * dpph * Herpes simplex virus * Nitric oxide * Syzygium jambos Subject RIV: EF - Botanics OBOR OECD: Oncology Impact factor: 1.427, year: 2016

  3. Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene-2-propylpentane hydrazide-hydrazones Derivatives

    Directory of Open Access Journals (Sweden)

    Ayman El-Faham

    2015-08-01

    Full Text Available Eight novel N′-(2-oxoindolin-3-ylidene-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR (1H-NMR and 13C-NMR, elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2 and leukaemia (Jurkat, as well as in normal cell lines derived from human embryonic kidney (HEK293 using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32–50 μM. Among the tested compounds, 4a showed specificity against leukaemia (Jurkat cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.

  4. Anticancer Activity of Chloroform Extract and Sub-fractions of Nepeta deflersiana on Human Breast and Lung Cancer Cells: An In vitro Cytotoxicity Assessment.

    Science.gov (United States)

    Al-Oqail, Mai M; Al-Sheddi, Ebtesam S; Siddiqui, Maqsood A; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; Farshori, Nida N

    2015-10-01

    Cancer is one of the major causes of death worldwide. The plant-derived natural products have received considerable attention in recent years due to their diverse pharmacological properties including anticancer effects. Nepeta deflersiana (ND) is used in the folk medicine as antiseptic, carminative, antimicrobial, antioxidant, and for treating rheumatic disorders. However, the anticancer activity of ND chloroform extract has not been explored so far. The present study was aimed to investigate the anticancer activities of chloroform Nepeta deflersiana extract and various sub-fractions (ND-1-ND-15) of ND against human breast cancer cells (MCF-7) and human lung cancer cells (A-549). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and neutral red uptake assays, and cellular morphological alterations using phase contrast light microscope were studied. Cells were exposed with 10-1000 μg/ml of sub-fractions of ND for 24 h. Results showed that selected sub-fractions of the chloroform extract significantly reduced the cell viability of MCF-7 and A-549 cells, and altered the cellular morphology in a concentration-dependent manner. Among the sub-fractions, ND-10 fraction showed relatively higher cytotoxicity compared to other fractions whereas, ND-1 did not cause any cytotoxicity even at higher concentrations. The A-549 cells were found to be more sensitive to growth inhibition by all the extracts as compared to the MCF-7 cells. The present study provides preliminary screening of anticancer activities of chloroform extract and sub-fractions of ND, which can be further used for the development of a potential therapeutic anticancer agent. Nepeta deflersiana extract exhibit cytotoxicity and altered the cellular morphology. Sub-fractions of the chloroform extract of Nepeta deflersiana reduced the cell viability of MCF-7 and A-549 cells. Among the sub-fractions, ND-10 fraction showed relatively higher cytotoxicity. The A-549 cells were found to be more sensitive

  5. Synthesis and Anticancer Activity of New 1-Thia-4-azaspiro[4.5]decane, Their Derived Thiazolopyrimidine and 1,3,4-Thiadiazole Thioglycosides

    Directory of Open Access Journals (Sweden)

    Eman M. Flefel

    2017-01-01

    Full Text Available New 1-thia-azaspiro[4.5]decane derivatives, their derived thiazolopyrimidine and 1,3,4-thiadiazole compounds were synthesized. The thioglycoside derivatives of the synthesized (1,3,4-thiadiazolylthiaazaspiro[4.5]decane and thiazolopyrimidinethione compounds were synthesized by glycosylation reactions using acetylated glycosyl bromides. The anticancer activity of synthesized compounds was studied against the cell culture of HepG-2 (human liver hepatocellular carcinoma, PC-3 (human prostate adenocarcinoma and HCT116 (human colorectal carcinoma cell lines and a number of compounds showed moderate to high inhibition activities.

  6. New carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, X-ray crystallography and anticancer activity.

    Science.gov (United States)

    Tănase, Constantin I; Drăghici, Constantin; Căproiu, Miron Teodor; Shova, Sergiu; Mathe, Christophe; Cocu, Florea G; Enache, Cristian; Maganu, Maria

    2014-01-01

    An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane skeleton in the sugar moiety. X-ray crystallography confirmed an exo-coupling of base to the ring and a L configuration of the nucleoside analogues. The compounds were tested for anticancer activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. The tricarboxylic acid cycle activity in cultured primary astrocytes is strongly accelerated by the protein tyrosine kinase inhibitor tyrphostin 23

    DEFF Research Database (Denmark)

    Hohnholt, Michaela C; Blumrich, Eva-Maria; Waagepetersen, Helle S

    2017-01-01

    production. In addition, T23-treatment strongly increased the molecular carbon labeling of the TCA cycle intermediates citrate, succinate, fumarate and malate, and significantly increased the incorporation of (13)C-labelling into the amino acids glutamate, glutamine and aspartate. These results clearly......Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases and has been considered as potential anti-cancer drug. T23 was recently reported to acutely stimulate the glycolytic flux in primary cultured astrocytes. To investigate whether T23 also affects the tricarboxylic acid (TCA...

  8. Oral nano-delivery of anticancer ginsenoside 25-OCH3-PPD, a natural inhibitor of the MDM2 oncogene: Nanoparticle preparation, characterization, in vitro and in vivo anti-prostate cancer activity, and mechanisms of action.

    Science.gov (United States)

    Voruganti, Sukesh; Qin, Jiang-Jiang; Sarkar, Sushanta; Nag, Subhasree; Walbi, Ismail A; Wang, Shu; Zhao, Yuqing; Wang, Wei; Zhang, Ruiwen

    2015-08-28

    The Mouse Double Minute 2 (MDM2) oncogene plays a critical role in cancer development and progression through p53-dependent and p53-independent mechanisms. Both natural and synthetic MDM2 inhibitors have been shown anticancer activity against several human cancers. We have recently identified a novel ginsenoside, 25-OCH3-PPD (GS25), one of the most active anticancer ginsenosides discovered thus far, and have demonstrated its MDM2 inhibition and anticancer activity in various human cancer models, including prostate cancer. However, the oral bioavailability of GS25 is limited, which hampers its further development as an oral anticancer agent. The present study was designed to develop a novel nanoparticle formulation for oral delivery of GS25. After GS25 was successfully encapsulated into PEG-PLGA nanoparticles (GS25NP) and its physicochemical properties were characterized, the efficiency of MDM2 targeting, anticancer efficacy, pharmacokinetics, and safety were evaluated in in vitro and in vivo models of human prostate cancer. Our results indicated that, compared with the unencapsulated GS25, GS25NP demonstrated better MDM2 inhibition, improved oral bioavailability and enhanced in vitro and in vivo activities. In conclusion, the validated nano-formulation for GS25 oral delivery improves its molecular targeting, oral bioavailability and anticancer efficacy, providing a basis for further development of GS25 as a novel agent for cancer therapy and prevention.

  9. Au/TiO2 nanobelt heterostructures for the detection of cancer cells and anticancer drug activity by potential sensing

    International Nuclear Information System (INIS)

    Cui, Jingjie; Xu, Ping; Li, Hong; Chen, Jing; Chen, Shaowei; Gao, Li

    2016-01-01

    Cancer is a cell dysfunction disease. The detection of cancer cells is extremely important for early diagnosis and clinical treatments. At present, the pretreatment for the detection of cancer cells is costly, complicated and time-consuming. As different species of the analytes may give rise to specific voltammetric signals at distinctly different potentials, simple potential sensing has the specificity to detect different cellular species. By taking advantage of the different electrochemical characteristics of normal cells, cancer cells and biointeractions between anticancer drugs and cancer cells, we develop a specific, sensitive, direct, cost-effective and rapid method for the detection of cancer cells by electrochemical potential sensing based on Au/TiO 2 nanobelt heterostructure electrodes that will be of significance in early cancer diagnosis, in vitro screening of anticancer drugs  and molecular biology research. (paper)

  10. Exceptionally strong sorption of infochemicals to activated carbon reduces their bioavailability to fish

    NARCIS (Netherlands)

    Jonker, Michiel T O; van Mourik, Louise

    2014-01-01

    The addition of activated carbon (AC) to sediments is a relatively new approach to remediate contaminated sites. Activated carbon strongly sorbs hydrophobic organic contaminants, thereby reducing their bioavailability and uptake in organisms. Because of its high sorption capacity, AC might, however,

  11. Hair Growth Promoting and Anticancer Effects of p21-activated kinase 1 (PAK1 Inhibitors Isolated from Different Parts of Alpinia zerumbet

    Directory of Open Access Journals (Sweden)

    Nozomi Taira

    2017-01-01

    Full Text Available PAK1 (p21-activated kinase 1 is an emerging target for the treatment of hair loss (alopecia and cancer; therefore, the search for PAK1 blockers to treat these PAK1-dependent disorders has received much attention. In this study, we evaluated the anti-alopecia and anticancer effects of PAK1 inhibitors isolated from Alpinia zerumbet (alpinia in cell culture. The bioactive compounds isolated from alpinia were found to markedly promote hair cell growth. Kaempferol-3-O-β-d-glucuronide (KOG and labdadiene, two of the isolated compounds, increased the proliferation of human follicle dermal papilla cells by approximately 117%–180% and 132%–226%, respectively, at 10–100 μM. MTD (2,5-bis(1E,3E,5E-6-methoxyhexa-1,3,5-trien-1-yl-2,5-dihydrofuran and TMOQ ((E-2,2,3,3-tetramethyl-8-methylene-7-(oct-6-en-1-yloctahydro-1H-quinolizine showed growth-promoting activity around 164% and 139% at 10 μM, respectively. The hair cell proliferation induced by these compounds was significantly higher than that of minoxidil, a commercially available treatment for hair loss. Furthermore, the isolated compounds from alpinia exhibited anticancer activity against A549 lung cancer cells with IC50 in the range of 67–99 μM. Regarding the mechanism underlying their action, we hypothesized that the anti-alopecia and anticancer activities of these compounds could be attributed to the inhibition of the oncogenic/aging kinase PAK1.

  12. Anticancer activity and apoptosis inducing effect of methanolic extract of Cordia dichotoma against human cancer cell line

    OpenAIRE

    Md. Azizur Rahman; Arshad Hussain

    2015-01-01

    MTT assay and DAPI staining test were performed to evaluate anticancer potential and to assess apoptosis inducing effect of methanolic extract of Cordia dichotoma leaves (MECD) against human cervical cancer cell line (HeLa). Changes in MMP and intracellular ROS level were also assessed by JC-1 and DCFH-DA staining. Total phenolic contents were determined by colorimetric principle. Levels of statistical significance were determined by one-way analysis of variance followed by Dunnett’s posttest...

  13. In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity.

    Science.gov (United States)

    Sakr, Tamer M; Khedr, Mohammed A; Rashed, Hassan M; Mohamed, Maged E

    2018-02-23

    l-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs), this study focuses on investigating the possibility of repurposing phosphinothricin as a bisphosphonate analogue, particularly in two medicine-related activities: image probing and as an anti-cancer drug. As BP is a competitive inhibitor of human farnesyl pyrophosphate synthase (HFPPS), in silico molecular docking and dynamic simulations studies were established to evaluate the binding and stability of phosphinothricin with HFPPS, while the results showed good binding and stability in the active site of the enzyme in relation to alendronate. For the purpose of inspecting bone-tissue accumulation of phosphinothricin, a technetium ( 99m Tc)-phosphinothricin complex was developed and its stability and tissue distribution were scrutinized. The radioactive complex showed rapid, high and sustained uptake into bone tissues. Finally, the cytotoxic activity of phosphinothricin was tested against breast and lung cancer cells, with the results indicating cytotoxic activity in relation to alendronate. All the above results provide support for the use of phosphinothricin as a potential anti-cancer drug and of its technetium complex as an imaging probe.

  14. In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity

    Directory of Open Access Journals (Sweden)

    Tamer M. Sakr

    2018-02-01

    Full Text Available l-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl phosphinyl butyric acid ammonium salt (AHPB, which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs, this study focuses on investigating the possibility of repurposing phosphinothricin as a bisphosphonate analogue, particularly in two medicine-related activities: image probing and as an anti-cancer drug. As BP is a competitive inhibitor of human farnesyl pyrophosphate synthase (HFPPS, in silico molecular docking and dynamic simulations studies were established to evaluate the binding and stability of phosphinothricin with HFPPS, while the results showed good binding and stability in the active site of the enzyme in relation to alendronate. For the purpose of inspecting bone-tissue accumulation of phosphinothricin, a technetium (99mTc–phosphinothricin complex was developed and its stability and tissue distribution were scrutinized. The radioactive complex showed rapid, high and sustained uptake into bone tissues. Finally, the cytotoxic activity of phosphinothricin was tested against breast and lung cancer cells, with the results indicating cytotoxic activity in relation to alendronate. All the above results provide support for the use of phosphinothricin as a potential anti-cancer drug and of its technetium complex as an imaging probe.

  15. Liposomal solubilization of new 3-hydroxy-quinolinone derivatives with promising anticancer activity: a screening method to identify maximum incorporation capacity

    DEFF Research Database (Denmark)

    Di Cagno, Massimiliano; Styskala, Jakub; Hlaváč, Jan

    2011-01-01

    Four new 3-hydroxy-quinolinone derivatives with promising anticancer activity could be solubilized using liposomes as vehicle to an extent that allows their in vitro and in vivo testing without use of toxic solvent(s). A screening method to identify the maximum incorporation capacity of hydrophobic......, resulting in a 200-500-fold increase in apparent solubility. Drug-to-lipid ratios in the range of 2-5 µg/mg were obtained. Interestingly, the four quinolinone derivatives have shown different association tendencies with liposomes, probably due to the physicochemical properties of the different group bonded...

  16. Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells.

    Science.gov (United States)

    Lo Re, Oriana; Panebianco, Concetta; Porto, Stefania; Cervi, Carlo; Rappa, Francesca; Di Biase, Stefano; Caraglia, Michele; Pazienza, Valerio; Vinciguerra, Manlio

    2018-02-01

    Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. A 24 hr fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cytometry. Expression of lypolysaccharide (LPS)-induced activation markers (vimentin, αSMA) was evaluated by qPCR and immunoblotting. Liver fibrosis and inflammation were evaluated in a mouse model of steatohepatitis exposed to cycles of fasting, by histological and biochemical analyses. A 24 hr fasting-induced changes were also analyzed on the proliferation/viability/glucose uptake of human HCC cells exposed to Sorafenib. An expression panel of genes involved in survival, inflammation, and metabolism was examined by qPCR in HCC cells exposed to fasting and/or Sorafenib. Fasting decreased the proliferation and the activation of HSC. Repeated cycles of short term starvation were safe in mice but did not improve fibrosis. Fasting synergized with Sorafenib in hampering HCC cell growth and glucose uptake. Finally, fasting normalized the expression levels of genes which are commonly altered by Sorafenib in HCC cells. Fasting or fasting-mimicking diet diets should be evaluated in preclinical studies as a mean to potentiate the activity of Sorafenib in clinical use. © 2017 Wiley Periodicals, Inc.

  17. KCN1, a novel synthetic sulfonamide anticancer agent: in vitro and in vivo anti-pancreatic cancer activities and preclinical pharmacology.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available The purpose of the present study was to determine the in vitro and in vivo anti-cancer activity and pharmacological properties of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-ylmethyl]-N-phenylbenzenesulfonamide, KCN1. In the present study, we investigated the in vitro activity of KCN1 on cell proliferation and cell cycle distribution of pancreatic cancer cells, using the MTT and BrdUrd assays, and flow cytometry. The in vivo anti-cancer effects of KCN1 were evaluated in two distinct xenograft models of pancreatic cancer. We also developed an HPLC method for the quantitation of the compound, and examined its stability in mouse plasma, plasma protein binding, and degradation by mouse S9 microsomal enzymes. Furthermore, we examined the pharmacokinetics of KCN1 following intravenous or intraperitoneal injection in mice. Results showed that, in a dose-dependent manner, KCN1 inhibited cell growth and induced cell cycle arrest in human pancreatic cancer cells in vitro, and showed in vivo anticancer efficacy in mice bearing Panc-1 or Mia Paca-2 tumor xenografts. The HPLC method provided linear detection of KCN1 in all of the matrices in the range from 0.1 to 100 µM, and had a lower limit of detection of 0.085 µM in mouse plasma. KCN1 was very stable in mouse plasma, extensively plasma bound, and metabolized by S9 microsomal enzymes. The pharmacokinetic studies indicated that KCN1 could be detected in all of the tissues examined, most for at least 24 h. In conclusion, our preclinical data indicate that KCN1 is a potential therapeutic agent for pancreatic cancer, providing a basis for its future development.

  18. Multiple QSAR models, pharmacophore pattern and molecular docking analysis for anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues

    Science.gov (United States)

    Masand, Vijay H.; El-Sayed, Nahed N. E.; Bambole, Mukesh U.; Quazi, Syed A.

    2018-04-01

    Multiple discrete quantitative structure-activity relationships (QSARs) models were constructed for the anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues with a variety of substituents like sbnd Br, sbnd OH, -OMe, etc. at different positions. A big pool of descriptors was considered for QSAR model building. Genetic algorithm (GA), available in QSARINS-Chem, was executed to choose optimum number and set of descriptors to create the multi-linear regression equations for a dataset of sixty-nine compounds. The newly developed five parametric models were subjected to exhaustive internal and external validation along with Y-scrambling using QSARINS-Chem, according to the OECD principles for QSAR model validation. The models were built using easily interpretable descriptors and accepted after confirming statistically robustness with high external predictive ability. The five parametric models were found to have R2 = 0.80 to 0.86, R2ex = 0.75 to 0.84, and CCCex = 0.85 to 0.90. The models indicate that frequency of nitrogen and oxygen atoms separated by five bonds from each other and internal electronic environment of the molecule have correlation with the anticancer activity.

  19. Exploring the physicochemical profile and the binding patterns of selected novel anticancer Himalayan plant derived active compounds with macromolecular targets

    Directory of Open Access Journals (Sweden)

    Arun Bahadur Gurung

    Full Text Available Plants are vital source of compounds offering plethora of therapeutic effects against various ailments without much side effects. Due to wide spread prevalence and drug resistance in cancer; there is an urgent need for discovery of new anti-cancer drugs. In the present study, selected novel anti-cancer plants derived compounds (cmpd1 to cmpd15 from Himalayan region were docked with defined molecular targets that regulate cell proliferation and apoptosis. The binding energies of best docked compounds ranged between −8.0 kcal/mol and −11.71 kcal/mol. Further analysis revealed critical hydrogen bonds and hydrophobic interactions between compounds and targets. The best docked compounds viz., cmpd15 against cyclin-dependent kinase-2 (CDK-2, cmpd8 against CDK-6 and cmpd9 against Topoisomerase I and II showed higher binding affinities than the native co-crystal ligands. The root mean square deviation (RMSD and potential energy plot clearly indicates the stability of the complexes during 20 ns molecular dynamics (MD simulation. The Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA binding energy analysis revealed Van der Waals energy component which is the principal stabilizing energy for their interactions except CDK-2/cmpd15 complex. The polar solvation energy did not have favorable contribution to their stabilization. The binding energy decomposition analysis revealed per residue contribution for each docked complexes. Physicochemical profile studies showed that majority of the compounds conform to Lipinski's rule of five (ROF having low to high blood brain barrier (BBB penetration, human intestinal absorption, plasma binding protein inhibition and P glycoprotein inhibition. Keywords: ADMET, Anticancer, MM/PBSA, Molecular docking, Molecular dynamics simulation and plant derived compounds

  20. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4 + T cells

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Guangwen; Yang, Tianming [College of Pharmacy, South-Central University for Nationalities, Wuhan (China); Wang, Chaoyuan [College of Life Science, South-Central University for Nationalities, Wuhan (China); Su, Hanwen, E-mail: suhanwen-1@163.com [Renmin Hospital of Wuhan University, Wuhan (China); Xiang, Meixian, E-mail: xiangmeixian99@163.com [College of Pharmacy, South-Central University for Nationalities, Wuhan (China)

    2013-06-15

    Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-κB activity in CD4 + T cells.

  1. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4 + T cells

    International Nuclear Information System (INIS)

    Shu, Guangwen; Yang, Tianming; Wang, Chaoyuan; Su, Hanwen; Xiang, Meixian

    2013-01-01

    Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4 + T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8 + T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4 + T cells but not in CD8 + T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4 + T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4 + T cells is implicated in its immunomodulatory activity. - Highlights: • Gastrodin stimulates anticancer immune response. • Gastrodin represses tumor transplantation-induced CD4 + T cell apoptosis. • Gastrodin activates NF-κB activity in CD4 + T cells

  2. Strong Broadband Terahertz Optical Activity through Control of the Blaschke Phase with Chiral Metasurfaces

    Science.gov (United States)

    Cole, Michael A.; Chen, Wen-chen; Liu, Mingkai; Kruk, Sergey S.; Padilla, Willie J.; Shadrivov, Ilya V.; Powell, David A.

    2017-07-01

    We demonstrate terahertz chiral metamaterials that achieve resonant transmission and strong optical activity. This response is realized in a metasurface coupled to its Babinet complement, with additional twist. Uniquely, the optical activity achieved in this type of metamaterial is weakly dispersive around the resonant transmission maxima, but it can be highly dispersive around the transmission minima. It has recently been shown that this unique optical activity response is closely related to zeros in the transmission spectra of circular polarizations through the Kramers-Kronig relations and strong resonant features in the optical activity spectrum corresponding to the Blaschke phase terms. Here we demonstrate how modifying the meta-atom geometry greatly affects the location and magnitude of these Blaschke phase terms. We study three different meta-atoms, which are variations on the simple cross structure. Their responses are measured using terahertz time-domain spectroscopy and analyzed via numerical simulations.

  3. Evaluation of Synergetic Anticancer Activity of Berberine and Curcumin on Different Models of A549, Hep-G2, MCF-7, Jurkat, and K562 Cell Lines

    Directory of Open Access Journals (Sweden)

    Acharya Balakrishna

    2015-01-01

    Full Text Available Ayurvedic system of medicine is using Berberis aristata and Curcuma longa herbs to treat different diseases including cancer. The study was performed to evaluate the synergetic anticancer activity of Berberine and Curcumin by estimating the inhibition of the cell proliferation by cytotoxicity assay using MTT method on specified human cell lines (A549, Hep-G2, MCF-7, Jurkat, and K562. All the cells were harvested from the culture and seeded in the 96-well assay plates at seeding density of 2.0 × 104 cells/well and were incubated for 24 hours. Test items Berberine with Curcumin (1 : 1, Curcumin 95% pure, and Berberine 95% pure were exposed at the concentrations of 1.25, 0.001, and 0.5 mg/mL, respectively, and incubated for a period of 48 hours followed by dispensing MTT solution (5 mg/mL. The cells were incubated at 37 ± 1°C for 4 hours followed by addition of DMSO for dissolving the formazan crystals and absorbance was read at 570 nm. Separate wells were prepared for positive control, controls (only medium with cells, and blank (only medium. The results had proven the synergetic anticancer activity of Berberine with Curcumin inducing cell death greater percentage of >77% when compared to pure curcumin with <54% and pure Berberine with <45% on average on all cell line models.

  4. Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition.

    Science.gov (United States)

    Sun, Danni; Liu, Hongchun; Dai, Xiaoyang; Zheng, Xingling; Yan, Juan; Wei, Rongrui; Fu, Xuhong; Huang, Min; Shen, Aijun; Huang, Xun; Ding, Jian; Geng, Meiyu

    2017-10-10

    Aspirin is associated with a reduced risk of cancer and delayed progression of malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mTOR signaling is believed to partially contribute to these anticancer effects, although the mechanism is unclear. In this study, we revealed the mechanism underlying the effects of aspirin on AMPK-mTOR signaling, and described a mechanism-based rationale for the use of aspirin in cancer therapy. We found that aspirin inhibited mTORC1 signaling through AMPK-dependent and -independent manners. Aspirin inhibited the AMPK-TSC pathway, thus resulting in the suppression of mTORC1 activity. In parallel, it directly disrupted the mTOR-raptor interaction. Additionally, the combination of aspirin and sorafenib showed synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK pathways. Aspirin and sorafenib showed synergetic anticancer efficacy in the SMMC-7721 model. Our study provides mechanistic insights and a mechanism-based rationale for the roles of aspirin in cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Amphiphilic lipid derivatives of 3'-hydroxyurea-deoxythymidine: preparation, properties, molecular self-assembly, simulation and in vitro anticancer activity.

    Science.gov (United States)

    Li, Miao; Qi, Shuo; Jin, Yiguang; Yao, Weishang; Zhang, Sa; Zhao, Jingyu

    2014-11-01

    Lipid derivatives of nucleoside analogs and their nanoassemblies have become the research hotspot due to their unique function in cancer therapy. Six lipid derivatives of 3'-hydroxyurea-deoxythymidine were prepared with zidovudine as the raw material. The 5'-substituted lipid chains in the derivatives were from the various fatty acids including octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid and octadecanoic acid corresponding to the derivatives OHT, DHT, DDHT, TDHT, HDHT and ODHT. The amphiphilic derivatives formed Langmuir monolayers at the air/water interface with different surface pressure-molecular area isotherms depending on the length of lipid chains. The nanoassemblies of OHT, DHT, DDHT, TDHT and HDHT and the nanoscale precipitates of ODHT were obtained after we injected their tetrahydrofuran solutions doped with hydrophilic long chained polymers into water. Electron microscopy showed that the morphology of nanoassemblies may be vesicles or nanotubes depending on the length of lipid chains. The shorter the lipid chains were, the softer the nanoassemblies. Computer simulation supported the experimental results. The nanoassemblies and the nanoscale precipitates showed much higher anticancer effects on SW620 cells than the parent drug hydroxyurea. The nanostructures of the derivatives are promising anticancer nanomedicines. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sultana Mehbuba Hossain

    2018-03-01

    Full Text Available Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells. Citrate- or succinate-modified CA particles were synthesized with different concentrations of sodium citrate or sodium succinate, respectively, in the absence or presence of doxorubicin. The drug loading efficiency of the particles and their cellular uptake were observed by quantifying fluorescence intensity. The average diameter and surface charge of the particles were determined using Zetasizer. Cell viability was assessed by MTT assay. Citrate-modified carbonate apatite (CMCA exhibited the highest (31.38% binding affinity for doxorubicin and promoted rapid cellular uptake of the drug, leading to the half-maximal inhibitory concentration 1000 times less than that of the free drug in MCF-7 cells. Hence, CMCA nanoparticles with greater surface area enhance cytotoxicity in different breast cancer cells by enabling higher loading and more efficient cellular uptake of the drug.

  7. Chemical characterization, antioxidant, immune-regulating and anticancer activities of a novel bioactive polysaccharide from Chenopodium quinoa seeds.

    Science.gov (United States)

    Hu, Yichen; Zhang, Jinming; Zou, Liang; Fu, Chaomei; Li, Peng; Zhao, Gang

    2017-06-01

    Chenopodium quinoa, a promising nutraceutical cereal, has attracted increasing research interest, yet its polysaccharides remains to get few systematic studies. In this study, we employed orthogonal experimental design to optimize the ultrasound-assisted extraction process for highest yield of C. quinoa polysaccharides. A novel C. quinoa polysaccharide (CQP) fraction with high content and low molecular weight (8852Da) was subsequently purified by column chromatography, constituted by galacturonic acid and glucose monosaccharides. The purified CQP exhibited significantly antioxidant effect against DPPH + and ABTS + , with even higher efficiency than some other reported polysaccharides. Moreover, CQP could promote the RAW264.7 macrophage proliferation, while suppress the nitri oxide production on inflammatory RAW264.7 macrophage in a dose- and time-dependent manner. In view of the pathological correlation of free radical, inflammation and carcinogenesis, the anticancer effect of CQP was further investigated on human liver cancer SMMC 7721 and breast cancer MCF-7 cells. Interestingly, CQP displayed cytotoxicity against cancer cells, while none proliferation inhibition on normal cells. These results suggest that the bioactive polysaccharide from C. quinoa provided the promising potential as a natural antioxidant, immune-regulating and anticancer candidate for food and even drug application. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Optimization protocol for the extraction of 6-gingerol and 6-shogaol from Zingiber officinale var. rubrum Theilade and improving antioxidant and anticancer activity using response surface methodology.

    Science.gov (United States)

    Ghasemzadeh, Ali; Jaafar, Hawa Z E; Rahmat, Asmah

    2015-07-30

    Analysis and extraction of plant matrices are important processes for the development, modernization, and quality control of herbal formulations. Response surface methodology is a collection of statistical and mathematical techniques that are used to optimize the range of variables in various experimental processes to reduce the number of experimental runs, cost , and time, compared to other methods. Response surface methodology was applied for optimizing reflux extraction conditions for achieving high 6-gingerol and 6-shogaol contents, and high antioxidant activity in Zingiber officinale var. rubrum Theilade . The two-factor central composite design was employed to determine the effects of two independent variables, namely extraction temperature (X1: 50-80 °C) and time (X2: 2-4 h), on the properties of the extracts. The 6-gingerol and 6-shogaol contents were measured using ultra-performance liquid chromatography. The antioxidant activity of the rhizome extracts was determined by means of the 1,1-diphenyl-2-picrylhydrazyl assay. Anticancer activity of optimized extracts against HeLa cancer cell lines was measured using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Increasing the extraction temperature and time induced significant response of the variables. The optimum extraction condition for all responses was at 76.9 °C for 3.4 h. Under the optimum condition, the corresponding predicted response values for 6-gingerol, 6-shogaol, and the antioxidant activity were 2.89 mg/g DW, 1.85 mg/g DW, and 84.3%, respectively. 6-gingerol and 6-shogaol were extracted under optimized condition to check the viability of the models. The values were 2.92 and 1.88 mg/g DW, and 84.0% for 6-gingerol, 6-shogaol, and the antioxidant activity respectively. The experimental values agreed with those predicted, thus indicating suitability of the models employed and the success of RSM in optimizing the extraction condition. With optimizing of reflux extraction

  9. cDNA Cloning, Overexpression, Purification and Pharmacologic Evaluation for Anticancer Activity of Ribosomal Protein L23A Gene (RPL23A from the Giant Panda

    Directory of Open Access Journals (Sweden)

    Si-Nan Zhang

    2012-02-01

    orientation for the research and development of cancer protein drugs as well as possible anti-cancer mechanisms. Further research is on going to determine the bioactive principle(s of recombinant protein RPL23A responsible for its anticancer activity.

  10. Identification of strong photometric activity in the components of LHS 1070

    OpenAIRE

    Almeida, L. A.; Jablonski, F.; Martioli, E.

    2010-01-01

    Activity in low-mass stars is an important ingredient in the evolution of such objects. Fundamental physical properties such as age, rotation, magnetic field are correlated with activity. Aims: We show that two components of the low-mass triple system LHS 1070 exhibit strong flaring activity. We identify the flaring components and obtained an improved astrometric solution for the LHS 1070 A/(B+C) system. Methods: Time-series CCD observations were used to monitor LHS 1070 in the B and I_C band...

  11. Thermally activated flux creep in strongly layered high-temperature superconductors

    International Nuclear Information System (INIS)

    Chakravarty, S.; Ivlev, B.I.; Ovchinnikov, Y.N.

    1990-01-01

    Thermal activation energies for single vortices and vortex bundles in the presence of a magnetic field parallel to the layers are calculated. The pinning considered is intrinsic and is due to the strongly layered structure of high-temperature superconductors. The magnetic field and the current dependence of the activation energy are studied in detail. The calculation of the activation energy is used to determine the current-voltage characteristic. It may be possible to observe the effects discussed in this paper in a pure enough sample

  12. Recent discoveries of anticancer flavonoids.

    Science.gov (United States)

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Plescia, Fabiana; Daidone, Giuseppe

    2017-12-15

    In this review we report the recent advances in anticancer activity of the family of natural occurring flavonoids, covering the time span of the last five years. The bibliographic data will be grouped, on the basis of biological information, in two great categories: reports in which the extract plants bioactivity is reported and the identification of each flavonoid is present or not, and reports in which the anticancer activity is attributable to purified and identified flavonoids from plants. Wherever possible, the targets and mechanisms of action as well as the structure-activity relationships of the molecules will be reported. Also, in the review it was thoroughly investigated the recent discovery on flavonoids containing the 2-phenyl-4H-chromen-4-one system even if some examples of unusual flavonoids, bearing a non-aromatic B-ring or other ring condensed to the base structure are reported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Trial Watch: Anticancer radioimmunotherapy.

    Science.gov (United States)

    Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-09-01

    Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in

  14. Vγ9Vδ2 T cell activation by strongly agonistic nucleotidic phosphoantigens.

    Science.gov (United States)

    Moulin, Morgane; Alguacil, Javier; Gu, Siyi; Mehtougui, Asmaa; Adams, Erin J; Peyrottes, Suzanne; Champagne, Eric

    2017-12-01

    Human Vγ9Vδ2 T cells can sense through their TCR tumor cells producing the weak endogenous phosphorylated antigen isopentenyl pyrophosphate (IPP), or bacterially infected cells producing the strong agonist hydroxyl dimethylallyl pyrophosphate (HDMAPP). The recognition of the phosphoantigen is dependent on its binding to the intracellular B30.2 domain of butyrophilin BTN3A1. Most studies have focused on pyrophosphate phosphoantigens. As triphosphate nucleotide derivatives are naturally co-produced with IPP and HDMAPP, we analyzed their specific properties using synthetic nucleotides derived from HDMAPP. The adenylated, thymidylated and uridylated triphosphate derivatives were found to activate directly Vγ9Vδ2 cell lines as efficiently as HDMAPP in the absence of accessory cells. These antigens were inherently resistant to terminal phosphatases, but apyrase, when added during a direct stimulation of Vγ9Vδ2 cells, abrogated their stimulating activity, indicating that their activity required transformation into strong pyrophosphate agonists by a nucleotide pyrophosphatase activity which is present in serum. Tumor cells can be sensitized with nucleotide phosphoantigens in the presence of apyrase to become stimulatory, showing that this can occur before their hydrolysis into pyrophosphates. Whereas tumors sensitized with HDMAPP rapidly lost their stimulatory activity, sensitization with nucleotide derivatives, in particular with the thymidine derivative, induced long-lasting stimulating ability. Using isothermal titration calorimetry, binding of some nucleotide derivatives to BTN3A1 intracellular domain was found to occur with an affinity similar to that of IPP, but much lower than that of HDMAPP. Thus, nucleotide phosphoantigens are precursors of pyrophosphate antigens which can deliver strong agonists intracellularly resulting in prolonged and strengthened activity.

  15. Biologically synthesised silver nanoparticles from three diverse family of plant extracts and their anticancer activity against epidermoid A431 carcinoma.

    Science.gov (United States)

    Nayak, Debasis; Pradhan, Sonali; Ashe, Sarbani; Rauta, Pradipta Ranjan; Nayak, Bismita

    2015-11-01

    Biological synthesis of silver nanoparticles is a cost effective natural process where the phytochemicals specifically phenols, flavonoids and terpenoids present in the plant extracts act as capping and reducing agent. Due to their nano size regime the silver nanoparticles may directly bind to the DNA of the pathogenic bacterial strains leading to higher antimicrobial activity. In the current study silver nanoparticles were synthesised using plant extracts from different origin Cucurbita maxima (petals), Moringa oleifera (leaves) and Acorus calamus (rhizome). The synthesised nanoparticles were characterized by UV-visible spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), field emission scanning electron microscopy (Fe-SEM) and Fourier transform infrared spectroscopy (FTIR). Highly crystalline, roughly spherical and cuboidal silver nanoparticles of 30-70 nm in size were synthesised. The nanoparticles provided strong antimicrobial activity against pathogenic strains. The effect of the synthesised nanoparticles against A431 skin cancer cell line was tested for their toxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. The IC50 values of 82.39±3.1, 83.57±3.9 and 78.58±2.7 μg/ml were calculated for silver nanoparticles synthesised by C. maxima, M. oleifera and A. calamus respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Characterization of the host–guest complex of a curcumin analog with β-cyclodextrin and β-cyclodextrin–gemini surfactant and evaluation of its anticancer activity

    Directory of Open Access Journals (Sweden)

    Poorghorban M

    2015-01-01

    Full Text Available Masoomeh Poorghorban,1 Umashankar Das,2 Osama Alaidi,1 Jackson M Chitanda,2 Deborah Michel,1 Jonathan Dimmock,1 Ronald Verrall,3 Pawel Grochulski,1,4 Ildiko Badea1 1Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, 2Department of Chemical and Biological Engineering, 3Department of Chemistry, University of Saskatchewan, Saskatoon, SK, Canada; 4Canadian Light Source, Saskatoon, SK, Canada Background: Curcumin analogs, including the novel compound NC 2067, are potent cytotoxic agents that suffer from poor solubility, and hence, low bioavailability. Cyclodextrin-based carriers can be used to encapsulate such agents. In order to understand the interaction between the two molecules, the physicochemical properties of the host–guest complexes of NC 2067 with β-cyclodextrin (CD or β-cyclodextrin–gemini surfactant (CDgemini surfactant were investigated for the first time. Moreover, possible supramolecular structures were examined in order to aid the development of new drug delivery systems. Furthermore, the in vitro anticancer activity of the complex of NC 2067 with CDgemini surfactant nanoparticles was demonstrated in the A375 melanoma cell line.Methods: Physicochemical properties of the complexes formed of NC 2067 with CD or CDgemini surfactant were investigated by synchrotron-based powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Synchrotron-based small- and wide-angle X-ray scattering and size measurements were employed to assess the supramolecular morphology of the complex formed by NC 2067 with CDgemini surfactant. Lastly, the in vitro cell toxicity of the formulations toward A375 melanoma cells at various drug-to-carrier mole ratios were measured by cell viability assay.Results: Physical mixtures of NC 2067 and CD or CDgemini surfactant showed characteristics of the individual components, whereas the complex of NC 2067 and CD or CDgemini surfactant presented new

  17. Green synthesis of silver and gold nanoparticles from Gymnema sylvestre leaf extract: study of antioxidant and anticancer activities

    Science.gov (United States)

    Nakkala, Jayachandra Reddy; Mata, Rani; Bhagat, Ekta; Sadras, Sudha Rani

    2015-03-01

    The present study reports the biological synthesis of silver and gold nanoparticles from Gymnema sylvestre leaf extract and their in vitro free radical scavenging efficacy as well as antiproliferative effect in Hep2 cells. The formation of silver (GYAgNPs) and gold nanoparticles (GYAuNPs) was confirmed by UV-visible spectroscopy. The average size of synthesized GYAgNPs and GYAuNPs was found to be 33 and 26 nm, respectively, by DLS particle size analyzer. TEM analysis indicated spherical shape of GYAgNPs and GYAuNPs and in EDX analysis they produced strong signal for silver and gold, respectively. Both GYAgNPs and GYAuNPs exhibited strong in vitro free radical quenching ability and their activity was comparable to that of GYLE. The cytotoxic effect of GYAgNPs and GYAuNPs in Hep2 cells was examined by MTT assay in which GYAgNPs displayed an IC50 value of 121 µg ml-1, while GYAuNPs produced up to 38 % of inhibition at the maximum concentration of 250 µg ml-1 used in this study. Distinct morphological changes were observed in Hep2 cells following treatment with GYAgNPs and GYAuNPs at 24 h, and orange-colored apoptotic bodies were located by acridine orange and ethidium bromide double-staining technique. Also, there was increase in the levels of reactive oxygen species in treated cells as indicated by 2',7'-dichlorofluorescin diacetate staining. Further, nuclear changes like chromatin condensation/fragmentation were also observed by propidium iodide and 4',6-diamidino-2-phenylindole dilactate staining methods. These findings support that the antiproliferative effects of GYAgNPs and GYAuNPs in Hep2 cells are mediated through induction of apoptosis.

  18. Green synthesis of silver and gold nanoparticles from Gymnema sylvestre leaf extract: study of antioxidant and anticancer activities

    Energy Technology Data Exchange (ETDEWEB)

    Nakkala, Jayachandra Reddy; Mata, Rani; Bhagat, Ekta; Sadras, Sudha Rani, E-mail: dr.ssrlab@gmail.com, E-mail: sadrassudha@gmail.com [Pondicherry University, Department of Biochemistry and Molecular Biology, School of Life Sciences (India)

    2015-03-15

    The present study reports the biological synthesis of silver and gold nanoparticles from Gymnema sylvestre leaf extract and their in vitro free radical scavenging efficacy as well as antiproliferative effect in Hep2 cells. The formation of silver (GYAgNPs) and gold nanoparticles (GYAuNPs) was confirmed by UV–visible spectroscopy. The average size of synthesized GYAgNPs and GYAuNPs was found to be 33 and 26 nm, respectively, by DLS particle size analyzer. TEM analysis indicated spherical shape of GYAgNPs and GYAuNPs and in EDX analysis they produced strong signal for silver and gold, respectively. Both GYAgNPs and GYAuNPs exhibited strong in vitro free radical quenching ability and their activity was comparable to that of GYLE. The cytotoxic effect of GYAgNPs and GYAuNPs in Hep2 cells was examined by MTT assay in which GYAgNPs displayed an IC{sub 50} value of 121 µg ml{sup −1}, while GYAuNPs produced up to 38 % of inhibition at the maximum concentration of 250 µg ml{sup −1} used in this study. Distinct morphological changes were observed in Hep2 cells following treatment with GYAgNPs and GYAuNPs at 24 h, and orange-colored apoptotic bodies were located by acridine orange and ethidium bromide double-staining technique. Also, there was increase in the levels of reactive oxygen species in treated cells as indicated by 2′,7′-dichlorofluorescin diacetate staining. Further, nuclear changes like chromatin condensation/fragmentation were also observed by propidium iodide and 4′,6-diamidino-2-phenylindole dilactate staining methods. These findings support that the antiproliferative effects of GYAgNPs and GYAuNPs in Hep2 cells are mediated through induction of apoptosis.

  19. Green synthesis of silver and gold nanoparticles from Gymnema sylvestre leaf extract: study of antioxidant and anticancer activities

    International Nuclear Information System (INIS)

    Nakkala, Jayachandra Reddy; Mata, Rani; Bhagat, Ekta; Sadras, Sudha Rani

    2015-01-01

    The present study reports the biological synthesis of silver and gold nanoparticles from Gymnema sylvestre leaf extract and their in vitro free radical scavenging efficacy as well as antiproliferative effect in Hep2 cells. The formation of silver (GYAgNPs) and gold nanoparticles (GYAuNPs) was confirmed by UV–visible spectroscopy. The average size of synthesized GYAgNPs and GYAuNPs was found to be 33 and 26 nm, respectively, by DLS particle size analyzer. TEM analysis indicated spherical shape of GYAgNPs and GYAuNPs and in EDX analysis they produced strong signal for silver and gold, respectively. Both GYAgNPs and GYAuNPs exhibited strong in vitro free radical quenching ability and their activity was comparable to that of GYLE. The cytotoxic effect of GYAgNPs and GYAuNPs in Hep2 cells was examined by MTT assay in which GYAgNPs displayed an IC 50 value of 121 µg ml −1 , while GYAuNPs produced up to 38 % of inhibition at the maximum concentration of 250 µg ml −1 used in this study. Distinct morphological changes were observed in Hep2 cells following treatment with GYAgNPs and GYAuNPs at 24 h, and orange-colored apoptotic bodies were located by acridine orange and ethidium bromide double-staining technique. Also, there was increase in the levels of reactive oxygen species in treated cells as indicated by 2′,7′-dichlorofluorescin diacetate staining. Further, nuclear changes like chromatin condensation/fragmentation were also observed by propidium iodide and 4′,6-diamidino-2-phenylindole dilactate staining methods. These findings support that the antiproliferative effects of GYAgNPs and GYAuNPs in Hep2 cells are mediated through induction of apoptosis

  20. Redox biotransformation and delivery of anthracycline anticancer antibiotics: How interpretable structure-activity relationships of lethality using electrophilicity and the London formula for dispersion interaction work.

    Science.gov (United States)

    Pang, Siu-Kwong

    2017-03-30

    Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted. In order to make a breakthrough, it was proposed that mechanistically interpretable molecular descriptors were used to correlate with biological activity to establish structure-activity plots. The mechanistically interpretable molecular descriptors used in this study include electrophilicity and the mathematical function in the London formula for dispersion interaction, and they were calculated using quantum chemical methods. The biological activity is the lethality of anthracycline anticancer antibiotics denoted as log LD50, which were obtained by intraperitoneal injection into mice. The results reveal that the plots for electrophilicity, which can be interpreted as redox reactivity of anthracyclines, can describe oxidative degradation for detoxification and reductive bioactivation for toxicity induction. The plots for the dispersion interaction function, which represent the attraction between anthracyclines and biomolecules, can describe efflux from and influx into target cells of toxicity. The plots can also identify three structural scaffolds of anthracyclines that have different metabolic pathways, resulting in their different toxicity behavior. This structure-dependent toxicity behavior revealed in the plots can provide perspectives on design of anthracycline anticancer antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Mitochondria and lipid raft-located FOF1-ATP synthase as major therapeutic targets in the antileishmanial and anticancer activities of ether lipid edelfosine.

    Directory of Open Access Journals (Sweden)

    Janny A Villa-Pulgarín

    2017-08-01

    Full Text Available Leishmaniasis is the world's second deadliest parasitic disease after malaria, and current treatment of the different forms of this disease is far from satisfactory. Alkylphospholipid analogs (APLs are a family of anticancer drugs that show antileishmanial activity, including the first oral drug (miltefosine for leishmaniasis and drugs in preclinical/clinical oncology trials, but their precise mechanism of action remains to be elucidated.Here we show that the tumor cell apoptosis-inducer edelfosine was the most effective APL, as compared to miltefosine, perifosine and erucylphosphocholine, in killing Leishmania spp. promastigotes and amastigotes as well as tumor cells, as assessed by DNA breakdown determined by flow cytometry. In studies using animal models, we found that orally-administered edelfosine showed a potent in vivo antileishmanial activity and diminished macrophage pro-inflammatory responses. Edelfosine was also able to kill Leishmania axenic amastigotes. Edelfosine was taken up by host macrophages and killed intracellular Leishmania amastigotes in infected macrophages. Edelfosine accumulated in tumor cell mitochondria and Leishmania kinetoplast-mitochondrion, and led to mitochondrial transmembrane potential disruption, and to the successive breakdown of parasite mitochondrial and nuclear DNA. Ectopic expression of Bcl-XL inhibited edelfosine-induced cell death in both Leishmania parasites and tumor cells. We found that the cytotoxic activity of edelfosine against Leishmania parasites and tumor cells was associated with a dramatic recruitment of FOF1-ATP synthase into lipid rafts following edelfosine treatment in both parasites and cancer cells. Raft disruption and specific FOF1-ATP synthase inhibition hindered edelfosine-induced cell death in both Leishmania parasites and tumor cells. Genetic deletion of FOF1-ATP synthase led to edelfosine drug resistance in Saccharomyces cerevisiae yeast.The present study shows that the

  2. Mass Spectrometry-Based Metabolomics of Agave Sap (Agave salmiana after Its Inoculation with Microorganisms Isolated from Agave Sap Concentrate Selected to Enhance Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Luis M. Figueroa

    2017-11-01

    Full Text Available Saponins have been correlated with the reduction of cancer cell growth and the apoptotic effect of agave sap concentrate. Empirical observations of this artisanal Mexican food have shown that fermentation occurs after agave sap is concentrated, but little is known about the microorganisms that survive after cooking, or their effects on saponins and other metabolites. The aim of this study was to evaluate the changes in metabolites found in agave (A. salmiana sap after its fermentation with microorganisms isolated from agave sap concentrate, and demonstrate its potential use to enhance anticancer activity. Microorganisms were isolated by dilution plating and identified by 16S rRNA analysis. Isolates were used to ferment agave sap, and their corresponding butanolic extracts were compared with those that enhanced the cytotoxic activity on colon (Caco-2 and liver (Hep-G2 cancer cells. Metabolite changes were investigated by mass spectrometry-based metabolomics. Among 69 isolated microorganisms, the actinomycetes Arthrobacter globiformis and Gordonia sp. were used to analyze the metabolites, along with bioactivity changes. From the 939 ions that were mainly responsible for variation among fermented samples at 48 h, 96 h, and 192 h, four were correlated to anticancer activity. It was shown that magueyoside B, a kammogenin glycoside, was found at higher intensities in the samples fermented with Gordonia sp. that reduced Hep-G2 viability better than controls. These findings showed that microorganisms from agave sap concentrate change agave sap metabolites such as saponins. Butanolic extracts obtained after agave sap fermentation with Arthrobacter globiformis or Gordonia sp. increased the cancer cell growth inhibitory effect on colon or liver cancer cells, respectively.

  3. Potential anti-cancer activity of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a histone deacetylase inhibitor, against breast cancer both in vitro and in vivo

    International Nuclear Information System (INIS)

    Park, Ki-Cheong; Kim, Seung-Won; Park, Ji-Hyun

    2011-01-01

    Histone deacetylase (HDAC) is an attractive target for cancer therapy because it plays a key role in gene expression and carcinogenesis. N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) is a novel synthetic HDAC inhibitor (HDACI) that shows better pharmacological properties than a known HDACI present in the human fibrosarcoma cell: suberoylanilide hydroxamic acid (SAHA). Here, we investigate the anti-cancer activity of HNHA against breast cancer both in vitro and in vivo. HNHA arrested the cell cycle at the G 1 /S phase via p21 induction, which led to profound inhibition of cancer cell growth in vitro. In addition, HNHA-treated cells showed markedly decreased levels of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α than SAHA and fumagillin (FUMA) when accompanied by increased histone acetylation. HNHA significantly inhibited tumor growth in an in vivo mouse xenograft model. HNHA-treated mice survived significantly longer than SAHA- and FUMA-treated mice. Dynamic MRI showed significantly decreased blood flow in the HNHA-treated mice, implying that HNHA inhibits tumor neovascularization. This finding was accompanied by marked reductions of proangiogenic factors and significant induction of angiogenesis inhibitors in tumor tissues. We have shown that HNHA is an effective anti-tumor agent in breast cancer cells in vitro and in breast cancer xenografts in vivo. Collectively, these findings indicate that HNHA may be a potent anti-cancer agent against breast cancer due to its multi-faceted inhibition of HDAC activity, as well as anti-angiogenesis activity. (author)

  4. Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

    International Nuclear Information System (INIS)

    Li, Jason Z.; Ke, Yuebin; Misra, Hara P.; Trush, Michael A.; Li, Y. Robert; Zhu, Hong; Jia, Zhenquan

    2014-01-01

    Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with

  5. Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jason Z. [Virginia Tech CRC, Blacksburg, VA (United States); Ke, Yuebin [Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Misra, Hara P. [Virginia Tech CRC, Blacksburg, VA (United States); Trush, Michael A. [Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (United States); Li, Y. Robert [Campbell University School of Osteopathic Medicine, Buies Creek, NC (United States); Virginia Tech-Wake Forest University SBES, Blacksburg, VA (United States); Department of Biology, University of North Carolina at Greensboro, NC (United States); Zhu, Hong, E-mail: zhu@campbell.edu [Campbell University School of Osteopathic Medicine, Buies Creek, NC (United States); Jia, Zhenquan, E-mail: z_jia@uncg.edu [Department of Biology, University of North Carolina at Greensboro, NC (United States)

    2014-12-15

    Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with

  6. Ag@Ag{sub 8}W{sub 4}O{sub 16} nanoroasted rice beads with photocatalytic, antibacterial and anticancer activity

    Energy Technology Data Exchange (ETDEWEB)

    Selvamani, Muthamizh; Krishnamoorthy, Giribabu; Ramadoss, Manigandan; Sivakumar, Praveen Kumar; Settu, Munusamy [Department of Inorganic Chemistry, University of Madras, Guindy Campus, Chennai, 600 025 (India); Ranganathan, Suresh [Department of Chemistry, SRM University, Ramapuram Campus, Chennai, 600 089 (India); Vengidusamy, Narayanan, E-mail: vnnara@yahoo.co.in [Department of Inorganic Chemistry, University of Madras, Guindy Campus, Chennai, 600 025 (India)

    2016-03-01

    Increasing resistance of pathogens and cancer cell line towards antibiotics and anticancer agents has caused serious health problems in the past decades. Due to these problems in recent years, researchers have tried to combine nanotechnology with material science to have intrinsic antimicrobial and anticancer activity. The metals and metal oxides were investigated with respect to their antimicrobial and anticancer effects towards bacteria and cancer cell line. In the present work metal@metal tungstate (Ag@Ag{sub 8}W{sub 4}O{sub 16} nanoroasted rice beads) is investigated for antibacterial activity against Escherichia coli and Staphylococcus aureus using Mueller-Hinton broth and the anticancer activity against B16F10 cell line was studied. Silver decorated silver tungstate (Ag@Ag{sub 8}W{sub 4}O{sub 16}) was synthesized by the microwave irradiation method using Cetyl Trimethyl Ammonium Bromide (CTAB). Ag@Ag{sub 8}W{sub 4}O{sub 16} was characterized by using various spectroscopic techniques. The phase and crystalline nature were analyzed by using XRD. The morphological analysis was carried out using Field Emission Scanning Electron Microscopy (FE-SEM), and High Resolution Transmission Electron Microscopy (HR-TEM). Further, Fourier Transform Infrared Spectroscopy (FT-IR) and Raman spectral analysis were carried out in order to ascertain the presence of functional groups in Ag@Ag{sub 8}W{sub 4}O{sub 16}. The optical property was investigated using Diffuse Reflectance Ultraviolet–Visible Spectroscopy (DRS-UV–Vis) and the band gap was found to be 3.08 eV. Surface area of the synthesized Ag@Ag{sub 8}W{sub 4}O{sub 16} wasanalyzed by BET analysis and Ag@Ag{sub 8}W{sub 4}O{sub 16} was utilized for the degradation of organic dyes methylene blue and rhodamine B. The morphology of the Ag@Ag{sub 8}W{sub 4}O{sub 16} resembles roasted rice beads with breath and length in nm range. The oxidation state of tungsten (W) and silver (Ag) was investigated using X-ray photoelectron

  7. In-vitro Anticancer and Antioxidant Activity of Gold Nanoparticles Conjugate with Tabernaemontana divaricata flower SMs Against MCF -7 Breast Cancer Cells

    International Nuclear Information System (INIS)

    Preetam, Raj J. P.; Purushothaman, M; Khusro, Ameer; Panicker, Shirly George

    2016-01-01

    Biologically stabilized gold nanoparticles were synthesized from the flower aqueous extract of T. divaricata. The synthesized nanoparticles were characterized by UV-Vis spectrophotometer, Zeta sizer, FTIR and TEM analysis. T. divaricata reduced gold nanoparticles having particle size and potential of 106.532 nm and -10.2 mV, respectively, with a characteristic peak of 550 nm in UV-visible spectrophotometer. FTIR graph after comparison between the crude flower extract and gold nanoparticles showed three major shifts in the functional groups. The morphology and size of the gold nanoparticles were examined by HRTEM analysis, which showed that most of the nanoparticles were nearly spherical with size of 100 nm. The gold nanoparticles synthesized demonstrated potent anticancer activity against MCF-7 cell line. The findings conclude that the antioxidant molecule present in T. divaricata may be responsible for both reduction and capping of gold nanoparticles which possess potential applications in medicine and pharmaceutical fields

  8. In-vitro Anticancer and Antioxidant Activity of Gold Nanoparticles Conjugate with Tabernaemontana divaricata flower SMs Against MCF -7 Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Preetam, Raj J. P.; Purushothaman, M; Khusro, Ameer; Panicker, Shirly George [PG Biotechnology, Tamil Nadu (India)

    2016-02-15

    Biologically stabilized gold nanoparticles were synthesized from the flower aqueous extract of T. divaricata. The synthesized nanoparticles were characterized by UV-Vis spectrophotometer, Zeta sizer, FTIR and TEM analysis. T. divaricata reduced gold nanoparticles having particle size and potential of 106.532 nm and -10.2 mV, respectively, with a characteristic peak of 550 nm in UV-visible spectrophotometer. FTIR graph after comparison between the crude flower extract and gold nanoparticles showed three major shifts in the functional groups. The morphology and size of the gold nanoparticles were examined by HRTEM analysis, which showed that most of the nanoparticles were nearly spherical with size of 100 nm. The gold nanoparticles synthesized demonstrated potent anticancer activity against MCF-7 cell line. The findings conclude that the antioxidant molecule present in T. divaricata may be responsible for both reduction and capping of gold nanoparticles which possess potential applications in medicine and pharmaceutical fields.

  9. Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture

    Directory of Open Access Journals (Sweden)

    Chien-Hsun Huang

    2015-09-01

    Full Text Available Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1–5 μM increased the activities of antioxidant enzymes catalase (CAT and superoxide dismutase (SOD from the reduction in melanoma cells. Also, hinokitiol (2–10 µM concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH· formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF, collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT.

  10. Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture.

    Science.gov (United States)

    Huang, Chien-Hsun; Jayakumar, Thanasekaran; Chang, Chao-Chien; Fong, Tsorng-Harn; Lu, Shing-Hwa; Thomas, Philip Aloysius; Choy, Cheuk-Sing; Sheu, Joen-Rong

    2015-09-25

    Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP)-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1-5 μM) increased the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in melanoma cells. Also, hinokitiol (2-10 µM) concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH·) formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF), collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT.

  11. Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo.

    Science.gov (United States)

    Zeng, Xingruo; Xu, Zhou; Gu, Jiayan; Huang, Haishan; Gao, Guangxun; Zhang, Xiaoru; Li, Jingxia; Jin, Honglei; Jiang, Guosong; Sun, Hong; Huang, Chuanshu

    2016-03-01

    Our recent studies found that isorhapontigenin (ISO) showed a significant inhibitory effect on human bladder cancer cell growth, accompanied with cell-cycle G0-G1 arrest as well as downregulation of Cyclin D1 expression at transcriptional level via inhibition of Sp1 transactivation in bladder cancer cells. In the current study, the potential ISO inhibition of bladder tumor formation has been explored in a xenograft nude mouse model, and the molecular mechanisms underlying ISO inhibition of Sp1 expression and anticancer activities have been elucidated both in vitro and in vivo. Moreover, the studies demonstrated that ISO treatment induced the expression of miR-137, which in turn suppressed Sp1 protein translation by directly targeting Sp1 mRNA 3'-untranslated region (UTR). Similar to ISO treatment, ectopic expression of miR-137 alone led to G0-G1 cell growth arrest and inhibition of anchorage-independent growth in human bladder cancer cells, which could be completely reversed by overexpression of GFP-Sp1. The inhibition of miR-137 expression attenuated ISO-induced inhibition of Sp1/Cyclin D1 expression, induction of G0-G1 cell growth arrest, and suppression of cell anchorage-independent growth. Taken together, our studies have demonstrated that miR-137 induction by ISO targets Sp1 mRNA 3'-UTR and inhibits Sp1 protein translation, which consequently results in reduction of Cyclin D1 expression, induction of G0-G1 growth arrest, and inhibition of anchorage-independent growth in vitro and in vivo. Our results have provided novel insights into understanding the anticancer activity of ISO in the therapy of human bladder cancer. ©2016 American Association for Cancer Research.

  12. Marine Microalgae with Anti-Cancer Properties.

    Science.gov (United States)

    Martínez Andrade, Kevin A; Lauritano, Chiara; Romano, Giovanna; Ianora, Adrianna

    2018-05-15

    Cancer is the leading cause of death globally and finding new therapeutic agents for cancer treatment remains a major challenge in the pursuit for a cure. This paper presents an overview on microalgae with anti-cancer activities. Microalgae are eukaryotic unicellular plants that contribute up to 40% of global primary productivity. They are excellent sources of pigments, lipids, carotenoids, omega-3 fatty acids, polysaccharides, vitamins and other fine chemicals, and there is an increasing demand for their use as nutraceuticals and food supplements. Some microalgae are also reported as having anti-cancer activity. In this review, we report the microalgal species that have shown anti-cancer properties, the cancer cell lines affected by algae and the concentrations of compounds/extracts tested to induce arrest of cell growth. We also report the mediums used for growing microalgae that showed anti-cancer activity and compare the bioactivity of these microalgae with marine anticancer drugs already on the market and in phase III clinical trials. Finally, we discuss why some microalgae can be promising sources of anti-cancer compounds for future development.

  13. Induction of oxidative DNA damage by mesalamine in the presence of copper: A potential mechanism for mesalamine anticancer activity

    International Nuclear Information System (INIS)

    Zimmerman, Ryan P.; Jia, Zhenquan; Zhu, Hong; Vandjelovic, Nathan; Misra, Hara P.; Wang, Jianmin; Li, Yunbo

    2011-01-01

    Mesalamine is the first line pharmacologic intervention for patients with ulcerative colitis, and recent epidemiologic studies have demonstrated a protective association between therapeutic use of the drug and colorectal carcinoma. However, the mechanism by which this protection is afforded has yet to be elucidated. Because copper is found at higher than normal concentrations in neoplastic cell nuclei and is known to interact with phenolic compounds to generate reactive oxygen species, we investigated whether the reaction of mesalamine/copper was able to induce oxidative DNA strand breaks in φX-174 RF I plasmid DNA, and the various components of the mechanism by which the reaction occurred. Plasmid DNA strand breaks were induced by pharmacologically relevant concentrations of mesalamine in the presence of a micromolar concentration of Cu(II), and damage was inhibited by bathocuproinedisulfonic acid (BCS) and catalase. Further, we showed that the reaction of copper with mesalamine consumed molecular oxygen, which was inhibited by BCS. Electron paramagnetic resonance spectral analysis of the reaction of copper/mesalamine indicated the presence of the hydroxyl radical, which was inhibited by both BCS and catalase. This study demonstrates for the first time that through a copper-redox cycling mechanism, the copper-mediated oxidation of mesalamine is a pro-oxidant interaction that generates hydroxyl radicals which may participate in oxidative DNA damage. These results demonstrate a potential mechanism of the anticancer effects of mesalamine in patients with ulcerative colitis.

  14. Synthesis and antimicrobial activity of guanylhydrazones. Synthesis of 2-(2-methylthio-2-aminovinyl)-1-methylpyridinium iodides and 2-(2-methylthio-2-aminovinyl)-1-methylquinolinium iodides as potential radioprotective and anticancer agents

    International Nuclear Information System (INIS)

    Almassian, B.

    1985-01-01

    The finding of appreciable antileukemic activity in a series of 2-(2-methylthio-2-amino)vinyl-1-methylquinolinium iodides (Foye et al., 1980, 1983) suggested that greater basicity, as compared with the corresponding dithioacetic acids, was contributing to the increase in activity. The addition of a greater degree of basicity in the design of anticancer possibilities in this series was considered worth investigation, particularly in view of the activity of a series of bis(quanylhydrazones) synthesized at Lederle Laboratories. Accordingly, a series of guanylhydrazones of 4-pyridine-,2-pyridine- and 4-quinolinecarboxyaldehydes was synthesized for anticancer as well as antibacterial screening. Also, substitution of additional basic functions in the 2-(2-methylthio-2-amino) vinyl-1-methylquinolinium and pyridinium iodide series has been made. Appreciable antimicrobial activities have been found with both 2-pyridine and 4-quinolinealdehyde guanylhydrazones, as well as with 2-(2-methylthio-2-amino)vinyl-1-methyl-pyridinium iodides. The overall approach to the synthesis of potential anticancer agents in this project is thus to observe the effect of increasing basicity of these compounds on DNA binding and anticancer activity

  15. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  16. Production, characterization and anticancer activity of Candida bombicola sophorolipids by means of solid state fermentation of sunflower oil cake and soybean oil

    Directory of Open Access Journals (Sweden)

    Rashad, M. M.

    2014-06-01

    Full Text Available The production of sophorolipids by Candida bombicola NRRL Y- 17069 grown in a mixture of sunflower oil cake and crude soybean oil as economic substrates with different fermentation techniques was studied. The highest yield (49.5 g·100 g−1 substrates was obtained from solid state fermentation after employing a new concept for extraction by methanol (E I followed by ethyl acetate (E II, then partially purified with hexane (E III. The course of time of fermentation was also studied, and E I extracted of the 12th day showed the minimum surface tension (45 mN·m−1 at a critical micelle dilution (CMD of 10% concentration. The produced sophorolipids were characterized and confirmed by FTIR and 1H NMR spectroscopy. The anticancer activity of the produced compounds was assessed against MCF-7, HepG2, A549, HCT116 cancer cell lines and the results revealed that E III and E IV (a mixture of E I & E III act as promising anticancer agents in HepG2 and A549 by inhibiting urokinase and histone deacetylase activities.Se estudió la producción de soforolípidos por Candida bombicola NRRL Y- 17069 cultiva con diferentes técnicas de fermentación en una mezcla de torta de girasol y aceite de soja crudo, como sustratos económicos. El rendimiento más alto (49,5 g·100 g−1 de sustrato se obtuvo por fermentación en estado sólido después de extraer con metanol (IE seguido de acetato de etilo (EII, y de purificación parcial con hexano (EIII. También se estudió el tiempo de fermentación, considerando que el extracto IE de 12 días mostró una tensión superficial mínima (45 mN·m−1 a una dilución micelar crítica (CMD de concentración 10 %. Los soforolípidos producidos se caracterizaron y se confirmaron mediante espectroscopia FTIR y RMN de 1H. La actividad anticancerígena de los compuestos producidos se evaluó en células MCF-7, HepG2, A549, líneas celulares de cáncer de HCT116 y los resultados revelaron que EIII y EIV (una mezcla de EI y EIII

  17. Development and evaluation of tocopherol-rich argan oil-based nanoemulsions as vehicles possessing anticancer activity.

    Science.gov (United States)

    Jordan, Melanie; Nayel, Amy; Brownlow, Bill; Elbayoumi, Tamer

    2012-12-01

    In recent years, diverse nanoemulsion vehicles (NEs) have been developed with vast potential for improving therapeutic index of clinically approved and experimental drugs. Using oils rich in omega-3 and omega-6 polyunsaturated fatty acids (PUFA), several promising nanoemulsion formulations have been developed recently for oral and systemic administration. The aim of our present work is to successfully develop and characterize optimized nanoemulsion platform, using the PUFA-rich argan oil that contain several important anti-inflammatory and antimitotic natural components. Using various emulsifying mixtures of polyethoxylated solutol HS-15 and polyethyleneglucol Vitamin E succinyl ester (TPGS), to form different NEs showing extended shelf-life stability. The physicochemical properties of prototype argan NEs were analyzed and utilizing a 32 full factorial design, followed by biocompatibility screen, using normal vascular myocytes and areolar fibroblasts. While 90-180 day stability of NEs correlated with TPGS:solutol surfactant blend ratios, adverse effects on integrity of test cultures were only noted at high TPGS content in the emulsifier system, exceeding 80%. Finally, the anti-proliferative efficacy of selected stable and acceptably biocompatible nanoscale TPGS-emulsified argan oil formulations was investigated using murine breast and colon carcinoma cells. The IC50 values of the combination of argan oil and TPGS (40-80% wt of emulsifiers) were 5-9 folds lower compared to TPGS-free and argan-oil free control NEs. Argan oil NE, stabilized with Vitamin E TPGS and solutol HS mixtures, demonstrated significant pro-apoptotic effect on both test cancer cell lines, indicating built-in anticancer properties for such NE platform, potentially enhancing overall antineoplastic effects of incorporated candidate chemotherapeutic agents.

  18. Arginine-rich histones have strong antiviral activity for influenza A viruses.

    Science.gov (United States)

    Hoeksema, Marloes; Tripathi, Shweta; White, Mitchell; Qi, Li; Taubenberger, Jeffery; van Eijk, Martin; Haagsman, Henk; Hartshorn, Kevan L

    2015-10-01

    While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular traps, where they play an important role in NET-mediated antimicrobial killing. Here, we show anti-influenza activity of histones against both seasonal H3N2 and H1N1, but not pandemic H1N1. The arginine rich histones, H3 and H4, had greater neutralizing and viral aggregating activity than the lysine rich histones, H2A and H2B. Of all core histones, histone H4 is most potent in neutralizing IAV, and incubation with IAV with histone H4 results in a decrease in uptake and viral replication by epithelial cells when measured by qRT-PCR. The antiviral activity of histone H4 is mediated principally by direct effects on viral particles. Histone H4 binds to IAV as assessed by ELISA and co-sedimentation of H4 with IAV. H4 also induces aggregation, as assessed by confocal microscopy and light transmission assays. Despite strong antiviral activity against the seasonal IAV strains, H4 was inactive against pandemic H1N1. These findings indicate a possible role for histones in the innate immune response against IAV. © The Author(s) 2015.

  19. Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid

    Science.gov (United States)

    Wiemuth, Dominik; Sahin, Hacer; Lefèvre, Cathérine M.T.; Wasmuth, Hermann E.; Gründer, Stefan

    2013-01-01

    Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA. PMID:23064163

  20. Synthesis of 2.5 nm colloidal iridium nanoparticles with strong surface enhanced Raman scattering activity

    International Nuclear Information System (INIS)

    Cui, Malin; Zhao, Yuan; Wang, Chan; Song, Qijun

    2016-01-01

    Colloidal iridium nanoparticles (IrNPs) were synthesized through an environmentally friendly approach by using trisodium citrate as the capping molecule in an aqueous medium. The resulting colloidal IrNPs have a typical diameter of 2.5 nm and display absorption bands at 250, 400 and 600 nm. They possess uniform morphology, good dispersibility, excellent stability in water, and exhibit strong surface enhanced Raman scattering (SERS) activity with an enhancement factor (EF) of 3.5 × 10 5 at the 1512 cm -1 peak when using Rhodamine 6G as the probe molecule. The excellent SERS performance of the IrNPs was exemplarily applied to the determination of the industrial colorant Sudan Red I. The peak intensity of the Raman band at 1236 cm -1 is linearly related to the concentration of Sudan Red I which can be determined by SERS in the 2 nM to 8 μM concentration range with a limit of detection as low as 0.6 nM. In our perception, this strong SERS activity of the IrNPs has a large potential in the SERS-based quantitation of various chemical substances. (author)

  1. Chandra and ALMA observations of the nuclear activity in two strongly lensed star-forming galaxies

    Science.gov (United States)

    Massardi, M.; Enia, A. F. M.; Negrello, M.; Mancuso, C.; Lapi, A.; Vignali, C.; Gilli, R.; Burkutean, S.; Danese, L.; Zotti, G. De

    2018-02-01

    Aim. According to coevolutionary scenarios, nuclear activity and star formation play relevant roles in the early stages of galaxy formation. We aim at identifying them in high-redshift galaxies by exploiting high-resolution and high-sensitivity X-ray and millimeter-wavelength data to confirm the presence or absence of star formation and nuclear activity and describe their relative roles in shaping the spectral energy distributions and in contributing to the energy budgets of the galaxies. Methods: We present the data, model, and analysis in the X-ray and millimeter (mm) bands for two strongly lensed galaxies, SDP.9 (HATLAS J090740.0-004200) and SDP.11 (HATLAS J091043.1-000322), which we selected in the Herschel-ATLAS catalogs for their excess emission in the mid-IR regime at redshift ≳1.5. This emission suggests nuclear activity in the early stages of galaxy formation. We observed both of them with Chandra ACIS-S in the X-ray regime and analyzed the high-resolution mm data that are available in the ALMA Science Archive for SDP.9. By combining the information available in mm, optical, and X-ray bands, we reconstructed the source morphology. Results: Both targets were detected in the X-ray, which strongly indicates highly obscured nuclear activity. ALMA observations for SDP.9 for the continuum and CO(6-5) spectral line with high resolution (0.02 arcsec corresponding to 65 pc at the distance of the galaxy) allowed us to estimate the lensed galaxy redshift to a better accuracy than pre-ALMA estimates (1.5753 ± 0.0003) and to model the emission of the optical, millimetric, and X-ray band for this galaxy. We demonstrate that the X-ray emission is generated in the nuclear environment, which strongly supports that this object has nuclear activity. On the basis of the X-ray data, we attempt an estimate of the black hole properties in these galaxies. Conclusions: By taking advantage of the lensing magnification, we identify weak nuclear activity associated with high

  2. Silver Nanoparticles Complexed with Bovine Submaxillary Mucin Possess Strong Antibacterial Activity and Protect against Seedling Infection.

    Science.gov (United States)

    Makarovsky, Daria; Fadeev, Ludmila; Salam, Bolaji Babajide; Zelinger, Einat; Matan, Ofra; Inbar, Jacob; Jurkevitch, Edouard; Gozin, Michael; Burdman, Saul

    2018-02-15

    A simple method for the synthesis of nanoparticles (NPs) of silver (Ag) in a matrix of bovine submaxillary mucin (BSM) was reported previously by some of the authors of this study. Based on mucin characteristics such as long-lasting stability, water solubility, and surfactant and adhesive characteristics, we hypothesized that these compounds, named BSM-Ag NPs, may possess favorable properties as potent antimicrobial agents. The goal of this study was to assess whether BSM-Ag NPs possess antibacterial activity, focusing on important plant-pathogenic bacterial strains representing both Gram-negative ( Acidovorax and Xanthomonas ) and Gram-positive ( Clavibacter ) genera. Growth inhibition and bactericidal assays, as well as electron microscopic observations, demonstrate that BSM-Ag NPs, at relatively low concentrations of silver, exert strong antimicrobial effects. Moreover, we show that treatment of melon seeds with BSM-Ag NPs effectively prevents seed-to-seedling transmission of Acidovorax citrulli , one of the most threatening pathogens of cucurbit production worldwide. Overall, our findings demonstrate strong antimicrobial activity of BSM-Ag NPs and their potential application for reducing the spread and establishment of devastating bacterial plant diseases in agriculture. IMPORTANCE Bacterial plant diseases challenge agricultural production, and the means available to manage them are limited. Importantly, many plant-pathogenic bacteria have the ability to colonize seeds, and seed-to-seedling transmission is a critical route by which bacterial plant diseases spread to new regions and countries. The significance of our study resides in the following aspects: (i) the simplicity of the method of BSM-Ag NP synthesis, (ii) the advantageous chemical properties of BSM-Ag NPs, (iii) the strong antibacterial activity of BSM-Ag NPs at relatively low concentrations of silver, and (iv) the fact that, in contrast to most studies on the effects of metal NPs on plant pathogens

  3. Molecular evolution of Theta-class glutathione transferase for enhanced activity with the anticancer drug 1,3-bis-(2-chloroethyl)-1-nitrosourea and other alkylating agents.

    Science.gov (United States)

    Larsson, Anna-Karin; Shokeer, Abeer; Mannervik, Bengt

    2010-05-01

    Glutathione transferase (GST) displaying enhanced activity with the cytostatic drug 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and structurally related alkylating agents was obtained by molecular evolution. Mutant libraries created by recursive recombination of cDNA coding for human and rodent Theta-class GSTs were heterologously expressed in Escherichia coli and screened with the surrogate substrate 4-nitrophenethyl bromide (NPB) for enhanced alkyltransferase activity. A mutant with a 70-fold increased catalytic efficiency with NPB, compared to human GST T1-1, was isolated. The efficiency in degrading BCNU had improved 170-fold, significantly more than with the model substrate NPB. The enhanced catalytic activity of the mutant GST was also 2-fold higher with BCNU than wild-type mouse GST T1-1, which is 80-fold more efficient than wild-type human GST T1-1. We propose that GSTs catalyzing inactivation of anticancer drugs may find clinical use in protecting sensitive normal tissues to toxic side-effects in treated patients, and as selectable markers in gene therapy. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke.

    Science.gov (United States)

    Van Kanegan, Michael J; Dunn, Denise E; Kaltenbach, Linda S; Shah, Bijal; He, Dong Ning; McCoy, Daniel D; Yang, Peiying; Peng, Jiangnan; Shen, Li; Du, Lin; Cichewicz, Robert H; Newman, Robert A; Lo, Donald C

    2016-05-12

    We previously reported neuroprotective activity of the botanical anti-cancer drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain slice and in vivo models of ischemic stroke. We showed that one component of this neuroprotective activity is mediated through its principal cardiac glycoside constituent, oleandrin, via induction of the potent neurotrophic factor brain-derived neurotrophic factor (BDNF). However, we also noted that the concentration-relation for PBI-05204 in the brain slice oxygen-glucose deprivation (OGD) model is considerably broader than that for oleandrin as a single agent. We thus surmised that PBI-05204 contains an additional neuroprotective component(s), distinct from oleandrin. We report here that neuroprotective activity is also provided by the triterpenoid constituents of PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of PBI-05204 (Fraction 0-4) containing oleanolic and other triterpenoids, but without cardiac glycosides, induces the expression of cellular antioxidant gene transcription programs regulated through antioxidant transcriptional response elements (AREs). Finally, we show that Fraction 0-4 provides broad neuroprotection in organotypic brain slice models for neurodegeneration driven by amyloid precursor protein (APP) and tau implicated in Alzheimer's disease and frontotemporal dementias, respectively, in addition to ischemic injury modeled by OGD.

  5. Chimerization of lactoferricin and lactoferrampin peptides strongly potentiates the killing activity against Candida albicans.

    Science.gov (United States)

    Bolscher, Jan; Nazmi, Kamran; van Marle, Jan; van 't Hof, Wim; Veerman, Enno

    2012-06-01

    Bovine lactoferrin harbors 2 antimicrobial sequences (LFcin and LFampin), situated in close proximity in the N1-domain. To mimic their semi parallel configuration we have synthesized a chimeric peptide (LFchimera) in which these sequences are linked in a head-to-head fashion to the α- and ε-amino group, respectively, of a single lysine. In line with previously described bactericidal effects, this peptide was also a stronger candidacidal agent than the antimicrobial peptides LFcin17-30 and LFampin265-284, or a combination of these 2. Conditions that strongly reduced the candidacidal activities of LFcin17-30 and LFampin265-284, such as high ionic strength and energy depletion, had little influence on the activity of LFchimera. Freeze-fracture electron microscopy showed that LFchimera severely affected the membrane morphology, resulting in disintegration of the membrane bilayer and in an efflux of small and high molecular weight molecules such as ATP and proteins. The differential effects displayed by the chimeric peptide and a mixture of its constituent peptides clearly demonstrate the synergistic effect of linking these peptides in a fashion that allows a similar spatial arrangement as in the parent protein, suggesting that in bovine lactoferrrin the corresponding fragments act in concert in its candidacidal activity.

  6. Motivational incentives lead to a strong increase in lateral prefrontal activity after self-control exertion.

    Science.gov (United States)

    Luethi, Matthias S; Friese, Malte; Binder, Julia; Boesiger, Peter; Luechinger, Roger; Rasch, Björn

    2016-10-01

    Self-control is key to success in life. Initial acts of self-control temporarily impair subsequent self-control performance. Why such self-control failures occur is unclear, with prominent models postulating a loss of a limited resource vs a loss of motivation, respectively. Here, we used functional magnetic resonance imaging to identify the neural correlates of motivation-induced benefits on self-control. Participants initially exerted or did not exert self-control. In a subsequent Stroop task, participants performed worse after exerting self-control, but not if they were motivated to perform well by monetary incentives. On the neural level, having exerted self-control resulted in decreased activation in the left inferior frontal gyrus. Increasing motivation resulted in a particularly strong activation of this area specifically after exerting self-control. Thus, after self-control exertion participants showed more prefrontal neural activity without improving performance beyond baseline level. These findings suggest that impaired performance after self-control exertion may not exclusively be due to a loss of motivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  7. Ethnomedicine Claim Directed in Silico Prediction of Anticancer ...

    African Journals Online (AJOL)

    2018-01-01

    Jan 1, 2018 ... 0.70, MACCS fingerprint), and the top 346 compounds it identified were identical to compounds with proven anticancer activity on 60 cell lines (23). Given such performance of. CDRUG, our finding can be taken as a preliminary evidence of anticancer activity by many of the medicinal plants used for treating.

  8. Synthesis, characterization and anticancer activity of gold(I) complexes that contain tri-tert-butylphosphine and dialkyl dithiocarbamate ligands

    KAUST Repository

    Altaf, Muhammad; Monim-ul-Mehboob, M.; Seliman, Adam A.A.; Sohail, Manzar; Wazeer, Mohammed I.M.; Isab, Anvarhusein A.; Li, L.; Dhuna, V.; Bhatia, G.; Dhuna, K.

    2015-01-01

    of both complexes was examined against A549 (lung cancer), MCF7 (breast cancer), and HeLa (cervical cancer) human cancer cell lines. Both complexes exhibit very strong in vitro cytotoxic effects against A549, MCF7 and HeLa cell lines. The screening

  9. Characterization and in vitro studies on anticancer, antioxidant activity against colon cancer cell line of gold nanoparticles capped with Cassia tora SM leaf extract

    Science.gov (United States)

    Abel, Ezra Elumalai; John Poonga, Preetam Raj; Panicker, Shirly George

    2016-01-01

    This study was aimed to determine the effectiveness of synthesized gold nanoparticles of an ethnobotanically and medicinally important plant species Cassia tora against colon cancer cells and to find its antibacterial and antioxidant activities. In order to improve the bioavailability of C. tora, we synthesized gold nanoparticles through green synthesis, by simple mixing and stirring of C. tora leaf powder and tetrachloroauric acid (HAuCl4) solution which gave a dispersion of gold nanoparticles conjugate with C. tora secondary metabolites (SMs) with characteristic surface plasmon resonance. It was characterized by Fourier transform infrared spectroscopy, zeta sizer, zeta potential and transmission electron microscopy. Antibacterial activity was carried out for gold nanoparticles conjugated with C. tora SMs, using well-diffusion method. The MTT assay for cell viability and markers such as catalase, nitric oxide and lipid peroxidation was predictable to confirm the cytotoxicity and antioxidant properties. The treatment of gold nanoparticles conjugated with C. tora SMs on Col320 cells showed reduction in the cell viability through MTT assay, and it also significantly suppressed the release of H2O2, LPO and NO production in a dose-dependent manner. C. tora SMs conjugate gold nanoparticles showed enhanced bioavailability, antioxidant and anticancer effect against colon cancer cell line (Col320).

  10. Pleuropterus multiflorus (Hasuo) mediated straightforward eco-friendly synthesis of silver, gold nanoparticles and evaluation of their anti-cancer activity on A549 lung cancer cell line.

    Science.gov (United States)

    Castro-Aceituno, Verónica; Abbai, Ragavendran; Moon, Seong Soo; Ahn, Sungeun; Mathiyalagan, Ramya; Kim, Yu-Jin; Kim, Yeon-Ju; Yang, Deok Chun

    2017-09-01

    Pleuropterus multiflorus (Hasuo) is a widely used medicinal plant in Korea and China for treating amnesia, isnomia, heart throbbing etc. With the constructive idea of promoting the wide-spread usage of P. multiflorus, we propose its indirect usage in the form of biologically active silver (Pm-AgNPs) and gold nanoparticles (Pm-AuNPs). The synthesized nanoparticles were predominantly spherical, crystalline with the Z-average hydrodynamic diameter of 274.8nm and 104.8nm respectively. Also, proteins and phenols were identified as the major players involved in their synthesis and stability. Further, Pm-AgNPs at 25μg/mL were significantly cytotoxic to lung cancer cells, whereas, Pm-AuNPs were not cytotoxic to both normal keratinocyte and lung cancer cells even at 100μg/mL. In addition, further evaluation of the anti-cancer activity of these new nanoparticles, such as migration and apoptosis, shown that Pm-AgNPs have a potential therapeutic effect on A549 lung cancer cell treatment. To the best of our knowledge, this is the first report dissecting out the ability of the endemic P. multiflorus for the synthesis of bioactive silver and gold nanoparticle which would open up doors for its extensive usage in medicinal field. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Synthesis and biological evaluation of isomeric methoxy substitutions on anti-cancer indolyl-pyridinyl-propenones: Effects on potency and mode of activity.

    Science.gov (United States)

    Trabbic, Christopher J; George, Sage M; Alexander, Evan M; Du, Shengnan; Offenbacher, Jennifer M; Crissman, Emily J; Overmeyer, Jean H; Maltese, William A; Erhardt, Paul W

    2016-10-21

    Certain indolyl-pyridinyl-propenone analogues kill glioblastoma cells that have become resistant to conventional therapeutic drugs. Some of these analogues induce a novel form of non-apoptotic cell death called methuosis, while others primarily cause microtubule disruption. Ready access to 5-indole substitution has allowed characterization of this position to be important for both types of mechanisms when a simple methoxy group is present. We now report the syntheses and biological effects of isomeric methoxy substitutions on the indole ring. Additionally, analogues containing a trimethoxyphenyl group in place of the pyridinyl moiety were evaluated for anticancer activity. The results demonstrate that the location of the methoxy group can alter both the potency and the mechanism of cell death. Remarkably, changing the methoxy from the 5-position to the 6-position switched the biological activity from induction of methuosis to disruption of microtubules. The latter may represent a prototype for a new class of mitotic inhibitors with potential therapeutic utility. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Anticancer drugs from marine flora: an overview.

    Science.gov (United States)

    Sithranga Boopathy, N; Kathiresan, K

    2010-01-01

    Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. The chemicals have displayed an array of pharmacological properties especially antioxidant, immunostimulatory, and antitumour activities. The phytochemicals possibly activate macrophages, induce apoptosis, and prevent oxidative damage of DNA, thereby controlling carcinogenesis. In spite of vast resources enriched with chemicals, the marine floras are largely unexplored for anticancer lead compounds. Hence, this paper reviews the works so far conducted on this aspect with a view to provide a baseline information for promoting the marine flora-based anticancer research in the present context of increasing cancer incidence, deprived of the cheaper, safer, and potent medicines to challenge the dreadful human disease.

  13. Anticancer activity of calyx of Diospyros kaki Thunb. through downregulation of cyclin D1 via inducing proteasomal degradation and transcriptional inhibition in human colorectal cancer cells.

    Science.gov (United States)

    Park, Su Bin; Park, Gwang Hun; Song, Hun Min; Son, Ho-Jun; Um, Yurry; Kim, Hyun-Seok; Jeong, Jin Boo

    2017-09-05

    Although it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. Anti-cell proliferative effect of 70% ethanol extracts from the calyx of Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β-catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

  14. In Silico and In Vitro Anticancer Activity of Isolated Novel Marker Compound from Chemically Modified Bioactive Fraction from Curcuma longa (NCCL).

    Science.gov (United States)

    Naqvi, Arshi; Malasoni, Richa; Gupta, Swati; Srivastava, Akansha; Pandey, Rishi R; Dwivedi, Anil Kumar

    2017-10-01

    Turmeric ( Curcuma longa ) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along with isolation and characterization of a novel marker compound (I). NCCL was prepared from HM. The chemical structure of the marker compound isolated from NCCL was determined from 1D/2D nuclear magnetic resonance, mass spectroscopy, and Fourier transform infrared. The compound so isolated was subjected to in silico and in vitro screenings to test its inhibitory effect on estrogen receptors. Molecular docking studies revealed that the binding poses of the compound I was energetically favorable. Among NCCL and compound I taken for in vitro studies, NCCL had exhibited good anti-cancer activity over compound I against MCF-7, MDA-MB-231, DU-145, and PC-3 cells. This is the first study about the synthesis of a chemically modified bioactive fraction which used a standardized extract since the preparation of the HM. It may be concluded that NCCL fraction having residual components induce more cell death than compound I alone. Thus, NCCL may be used as a potent therapeutic drug. In the present paper, a standardized hexane soluble fraction of Curcuma longa (HM) was chemically modified to give a novel bioactive fraction (NCCL). A novel marker compound was isolated from NCCL and was characerized using various spectral techniques. The compound so isolated was investigated for in-silico screenings. NCCL and isolated compound was subjected to in-vitro anti-cancer screenings against MCF 7, MDA MB 231 (breast adenocarcinoma) and DU 145 and PC 3 cell lines (androgen independent human prostate cancer cells). The virtual screenings reveals that isolated compound has shown favourable drug like properties. NCCL fraction having residual components induces more cell

  15. PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

    Science.gov (United States)

    Berg, Ingrid L; Neumann, Rita; Lam, Kwan-Wood G; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A; Jeffreys, Alec J

    2010-10-01

    PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice. PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots, with binding to this motif possibly triggering hot-spot activity via chromatin remodeling. We now report that human genetic variation at the PRDM9 locus has a strong effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Subtle changes within the zinc finger array can create hot-spot nonactivating or enhancing variants and can even trigger the appearance of a new hot spot, suggesting that PRDM9 is a major global regulator of hot spots in humans. Variation at the PRDM9 locus also influences aspects of genome instability-specifically, a megabase-scale rearrangement underlying two genomic disorders as well as minisatellite instability-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

  16. Anticancer Activity of Cobra Venom Polypeptide, Cytotoxin-II, against Human Breast Adenocarcinoma Cell Line (MCF-7) via the Induction of Apoptosis

    OpenAIRE

    Ebrahim, Karim; Shirazi, Farshad H.; Vatanpour, Hosein; zare, Abas; Kobarfard, Farzad; Rabiei, Hadi

    2014-01-01

    Purpose Breast cancer is a significant health problem worldwide, accounting for a quarter of all cancer diagnoses in women. Current strategies for breast cancer treatment are not fully effective, and there is substantial interest in the identification of novel anticancer agents especially from natural products including toxins. Cytotoxins are polypeptides found in the venom of cobras and have various physiological effects. In the present study, the anticancer potential of cytotoxin-II against...

  17. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  18. Anticancer Properties of Distinct Antimalarial Drug Classes

    Science.gov (United States)

    Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

    2013-01-01

    We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

  19. Cosmological Studies with Galaxy Clusters, Active Galactic Nuclei, and Strongly Lensed Quasars

    Science.gov (United States)

    Rumbaugh, Nicholas Andrew

    The large-scale structure (LSS) of the universe provides scientists with one of the best laboratories for studying Lambda Cold Dark Matter (LambdaCDM) cosmology. Especially at high redshift, we see increased rates of galaxy cluster and galaxy merging in LSS relative to the field, which is useful for studying the hierarchical merging predicted by LambdaCDM. The largest identified bound structures, superclusters, have not yet virialized. Despite the wide range of dynamical states of their constituent galaxies, groups, and clusters, they are all still actively evolving, providing an ideal laboratory in which to study cluster and galaxy evolution. In this dissertation, I present original research on several aspects of LSS and LambdaCDM cosmology. Three separate studies are included, each one focusing on a different aspect. In the first study, we use X-ray and optical observations from nine galaxy clusters at high redshift, some embedded in larger structures and some isolated, to study their evolutionary states. We extract X-ray gas temperatures and luminosities as well as optical velocity dispersions. These cluster properties are compared using low-redshift scaling relations. In addition, we employ several tests of substructure, using velocity histograms, Dressler-Shectman tests, and centroiding offsets. We conclude that two clusters out of our sample are most likely unrelaxed, and find support for deviations from self-similarity in the redshift evolution of the Lx-T relation. Our numerous complementary tests of the evolutionary state of clusters suggest potential under-estimations of systematic error in studies employing only a single such test. In the second study, we use multi-band imaging and spectroscopy to study active galactic nuclei (AGN) in high-redshift LSS. The AGN were identified using X-ray imaging and matched to optical catalogs that contained spectroscopic redshifts to identify members of the structures. AGN host galaxies tended to be associated with the

  20. Insights into the Intramolecular Properties of η6-Arene-Ru-Based Anticancer Complexes Using Quantum Calculations

    Directory of Open Access Journals (Sweden)

    Adebayo A. Adeniyi

    2013-01-01

    Full Text Available The factors that determine the stability and the effects of noncovalent interaction on the η6-arene ruthenium anticancer complexes are determined using DFT method. The intramolecular and intra-atomic properties were computed for two models of these half-sandwich ruthenium anticancer complexes and their respective hydrated forms. The results showed that the stability of these complexes depends largely on the network of hydrogen bonds (HB, strong nature of charge transfer, polarizability, and electrostatic energies that exist within the complexes. The hydrogen bonds strength was found to be related to the reported anticancer activities and the activation of the complexes by hydration. The metal–ligand bonds were found to be closed shell systems that are characterised by high positive Laplacian values of electron density. Two of the complexes are found to be predominantly characterised by LMCT while the other two are predominately characterised by MLCT.

  1. Investigation of nepetolide as a novel lead compound: Antioxidant, antimicrobial, cytotoxic, anticancer, anti-inflammatory, analgesic activities and molecular docking evaluation

    Directory of Open Access Journals (Sweden)

    Tanzeel ur Rehman

    2018-03-01

    Full Text Available In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from Nepeta suavis. Nepetolide concentration-dependently (1.0–1000 µg/mL exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus. In brine shrimp’s lethality model, nepetolide potently showed cytotoxic effect, with LC50 value of 8.7 µg/mL. When evaluated for antitumor activity in potato disc tumor assay, nepetolide exerted tumor inhibitory effect of 56.5 ± 1.5% at maximum tested concentration of 1000 µg/mL. Nepetolide at 20 mg/kg reduced carrageenan-induced inflammation (P < .001 vs. saline group in rat paw. Nepetolide dose-dependently (100–500 mg/kg decreased acetic acid evoked writhes, as exhibited by diclofenac sodium. In-silico investigation of nepetolide was carried out against cyclooxygenase-2, epidermal growth factor receptor and lipoxygenase-2 targets. Virtual screening through Patchdock online docking server identified primarily hydrophobic interactions between ligand nepetolide and receptors proteins. Enhanced hydrogen bonding was predicted with Autodock showing 6–8 hydrogen bonds per target. These results indicate that nepetolide exhibits antioxidant, antibacterial, cytotoxic, anticancer, anti-inflammatory and analgesic activities and should be considered as a lead compound for developing drugs for the remedy of oxidative stress-induced disorders, microbial infections, cancers, inflammations and pain.

  2. Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation.

    Science.gov (United States)

    Reyes-Reyes, E Merit; Šalipur, Francesca R; Shams, Mitra; Forsthoefel, Matthew K; Bates, Paula J

    2015-08-01

    AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. In the current study, we have investigated the significance and molecular mechanisms of AS1411-induced macropinocytosis. Our results indicate that the antiproliferative activity of AS1411 in various cell lines correlated with its capacity to stimulate macropinocytosis. In DU145 prostate cancer cells, AS1411 induced activation of EGFR, Akt, p38, and Rac1. Activation of Akt and p38 were not critical for AS1411 activity because Akt activation was not observed in all AS1411-responsive cell lines and knockdown of p38 had no effect on AS1411's ability to inhibit proliferation. On the other hand, activation of EGFR and Rac1 appeared to play a role in AS1411 activity in all cancer cell lines examined (DU145, MDA-MB-468, A549, LNCaP) and their inhibition significantly reduced AS1411-mediated macropinocytosis and AS1411 antiproliferative activity. Interestingly, downregulation of nucleolin expression by siRNA also produced a substantial increase in activated Rac1, revealing a previously unknown role for nucleolin as a negative regulator of Rac1 activation. Our results are consistent with a model whereby AS1411 binding to nucleolin leads to sustained activation of Rac1 and causes methuosis, a novel type of nonapoptotic cell death characterized by hyperstimulation of macropinocytosis. We speculate that methuosis is a tumor/metastasis suppressor mechanism that opposes the malignant functions of Rac1 and that

  3. Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma.

    Science.gov (United States)

    Cao, Yueyu; Qiao, Jing; Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

    2017-02-28

    Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides "killing" PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors.

  4. Design, synthesis and anticancer activity of diam(m)ine platinum(II) complexes bearing a small-molecular cell apoptosis inducer dichloroacetate.

    Science.gov (United States)

    Liu, Weiping; Jiang, Jing; Xu, Yongping; Hou, Shuqian; Sun, Liping; Ye, Qingsong; Lou, Liguang

    2015-05-01

    Four new diam(m)ine platinum complexes containing the dichloroacetate moiety in 3-dichoroacetoxylcyclobutane-1,1-dicarboxylate as the leaving group were synthesized, characterized by elemental analysis as well as by ESI(+)-MS (electrospray ionization mass spectrometry in positive mode), FT-IR, (1)H- and (13)C-NMR, and evaluated for their in vitro anticancer activity against human lung cancer cell line (A549) and ovarian cancer cell lines (SK-OV-3, SK-OV-3/DDP). Diam(m)ines used in the present study belong to the carriers of six clinically approved platinum drugs. Among the complexes synthesized, complex 2, cis-[Pt(II)(1R,2R-diaminocyclohexane)·(3-dichoroacetoxylcyclobutane-1,1-dicarboxylate)] is the most promising in terms of water solubility and potential of being totally devoid of cross-drug resistance with cisplatin. Therefore, complex 2 was selected for the dichloroacetate release test. The test shows dichloroacetate can be efficiently released from complex 2 under physiological conditions via the hydrolysis of an ester bond bridging the dichloroacetate moiety and platinum pharmacophores together. Our study supports the further evaluation of this complex as a drug candidate. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Synthesis and Anticancer Activity of Some Novel Tetralin-6-yl-pyrazoline, 2-Thioxopyrimidine, 2-Oxopyridine, 2-Thioxo-pyridine and 2-Iminopyridine Derivatives

    Directory of Open Access Journals (Sweden)

    Ebtehal S. Al-Abdullah

    2011-04-01

    Full Text Available The title compounds were prepared by reaction of 6-acetyltetralin (1 with different aromatic aldehydes 2a-c, namely 2,6-dichlorobenzaldehyde, 2,6-diflouro-benzaldehyde, and 3-ethoxy-4-hydroxybenzaldehyde, to yield the corresponding a,b-unsaturated ketones 3a-c. Compound 3b was reacted with hydrazine hydrate to yield the corresponding 2-pyrazoline 4, while compounds 3a,b reacted with thiourea to afford the 2-thioxopyrimidine derivatives 5a,b, respectively. The reaction of 1, and the aromatic aldehydes 2a-c with ethyl cyanoacetate, 2-cyano-thioacetamide or malononitrile in the presence of ammonium acetate yielded the corresponding 2-oxopyridines 6a,b, 2-thioxopyridines 7a-c or 2-iminopyridines 8a,b, respectively. The newly prepared compounds were evaluated for anticancer activity against two human tumor cell lines. Compound 3a showed the highest potency with IC50 = 3.5 and 4.5 μg/mL against a cervix carcinoma cell line (Hela and breast carcinoma cell line (MCF7, respectively.

  6. Cell type-specific anti-cancer properties of valproic acid: independent effects on HDAC activity and Erk1/2 phosphorylation

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Skladchikova, Galina; Lepekhin, Eugene E

    2010-01-01

    lines (BT4C, BT4Cn, U87MG, N2a, PC12-E2, CSML0, CSML100, HeLa, L929, Swiss 3T3). Results: VPA induced significant histone deacetylase (HDAC) inhibition in most of the cell lines, but the degree of inhibition was highly cell type-specific. Moreover, cell growth, motility and the degree of Erk1......ABSTRACT: BACKGROUND: The anti-epileptic drug valproic acid (VPA) has attracted attention as an anti-cancer agent. Methods: The present study investigated effects of VPA exposure on histone deacetylase (HDAC) inhibition, cell growth, cell speed, and the degree of Erk1/2 phosphorylation in 10 cell....../2 phosphorylation were inhibited, activated, or unaffected by VPA in a cell type-specific manner. Importantly, no relationship was found between the effects of VPA on HDAC inhibition and changes in the degree of Erk1/2 phosphorylation, cell growth, or motility. In contrast, VPA-induced modulation of the MAPK...

  7. Anticancer drugs during pregnancy.

    Science.gov (United States)

    Miyamoto, Shingo; Yamada, Manabu; Kasai, Yasuyo; Miyauchi, Akito; Andoh, Kazumichi

    2016-09-01

    Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Active galaxies. A strong magnetic field in the jet base of a supermassive black hole.

    Science.gov (United States)

    Martí-Vidal, Ivan; Muller, Sébastien; Vlemmings, Wouter; Horellou, Cathy; Aalto, Susanne

    2015-04-17

    Active galactic nuclei (AGN) host some of the most energetic phenomena in the universe. AGN are thought to be powered by accretion of matter onto a rotating disk that surrounds a supermassive black hole. Jet streams can be boosted in energy near the event horizon of the black hole and then flow outward along the rotation axis of the disk. The mechanism that forms such a jet and guides it over scales from a few light-days up to millions of light-years remains uncertain, but magnetic fields are thought to play a critical role. Using the Atacama Large Millimeter/submillimeter Array (ALMA), we have detected a polarization signal (Faraday rotation) related to the strong magnetic field at the jet base of a distant AGN, PKS 1830-211. The amount of Faraday rotation (rotation measure) is proportional to the integral of the magnetic field strength along the line of sight times the density of electrons. The high rotation measures derived suggest magnetic fields of at least tens of Gauss (and possibly considerably higher) on scales of the order of light-days (0.01 parsec) from the black hole. Copyright © 2015, American Association for the Advancement of Science.

  9. Aluminum nanostructures with strong visible-range SERS activity for versatile micropatterning of molecular security labels.

    Science.gov (United States)

    Lay, Chee Leng; Koh, Charlynn Sher Lin; Wang, Jing; Lee, Yih Hong; Jiang, Ruibin; Yang, Yijie; Yang, Zhe; Phang, In Yee; Ling, Xing Yi

    2018-01-03

    The application of aluminum (Al)-based nanostructures for visible-range plasmonics, especially for surface-enhanced Raman scattering (SERS), currently suffers from inconsistent local electromagnetic field distributions and/or inhomogeneous distribution of probe molecules. Herein, we lithographically fabricate structurally uniform Al nanostructures which enable homogeneous adsorption of various probe molecules. Individual Al nanostructures exhibit strong local electromagnetic field enhancements, in turn leading to intense SERS activity. The average SERS enhancement factor (EF) for individual nanostructures exceeds 10 4 for non-resonant probe molecules in the visible spectrum. These Al nanostructures also retain more than 70% of their original SERS intensities after one-month storage, displaying superb stability under ambient conditions. We further achieve tunable polarization-dependent SERS responses using anisotropic Al nanostructures, facilitating the design of sophisticated SERS-based security labels. Our micron-sized security label comprises two-tier security features, including a machine-readable hybrid quick-response (QR) code overlaid with a set of ciphertexts. Our work demonstrates the versatility of Al-based structures in low-cost modern chemical nano-analytics and forgery protection.

  10. Antimalarial, Anticancer, Antimicrobial Activities and Chemical Constituents of Essential Oil from the Aerial Parts of Cyperus kyllingia Endl.

    Directory of Open Access Journals (Sweden)

    Sorachai Khamsan

    2011-01-01

    Full Text Available The chemical constituents of the essential oil from Cyperus kyllingia Endl. were analyzed by a GC, GC-MS. Twenty-three compounds were identified, accounting for 93.75% of the total oil that consisted mainly of oxygenated sesquiterpenes (53.52%, particularly sesquiterpene hydrocarbons (38.97%, and carboxylic acid (1.26%. The most representative compounds were a -cadinol (19.32 %, caryophyllene oxide (12.17%, a -muurolol (11.58 %, a -humulene (9.85%, and a -atlantone (6.07%. The oil showed significant activities against Plasmodium falcipalum (K1, multi drug resistant strain and NCI-H187 (Small Cell Lung Cancer with the IC 50 values of 7.52 and 7.72 µg/mL, respectively. The oilexhibited highly active against Staphylococcus aureus ATCC25923 and moderately active against Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27553, Aspergillus flavus and Candida albicans.

  11. Anticancer Effect of AntiMalarial Artemisinin Compounds | Das ...

    African Journals Online (AJOL)

    A PubMed search of about 127 papers on anti‑cancer effects of antimalarials has revealed that this class of drug, including other antimalarials, have several biological characteristics that include anticancer properties. ... Keywords: Anticancer agents, Antimalarials, Antitumor activity, Artemisinins, Novel chemotherapy ...

  12. A New Water-Soluble Nanomicelle Formed through Self-Assembly of Pectin-Curcumin Conjugates: Preparation, Characterization, and Anticancer Activity Evaluation.

    Science.gov (United States)

    Bai, Feng; Diao, Jiajing; Wang, Ying; Sun, Shixin; Zhang, Hongmei; Liu, Yunyun; Wang, Yanqing; Cao, Jian

    2017-08-16

    Curcumin is a dominating active component of Curcuma longa and has been studied widely because of its prominent biological activities. The extremely low aqueous solubility, stability, and bioavailability of curcumin limit its application in the field of medicine. In this study, we developed pectin-curcumin (PEC-CCM) conjugates that could self-assemble water-soluble nanomicelles in aqueous solution. The structure of PEC-CCM conjugates was characterized by ultraviolet-visible spectra, fluorescence spectra, Fourier transform infrared spectroscopy, and 1 H nuclear magnetic resonance spectroscopy. The thermal property of PEC-CCM conjugates was investigated by thermogravimetric analysis. It was found that PEC-CCM conjugates had formed nanomicelles in aqueous medium via self-assembly. These nanomicelles were observed as small spheres or ellipsoids and aggregated with a size range of 70-190 nm by transmission electron microscopy analysis. In a solution of nanomicelles, the stability of curcumin was improved, and its antioxidant property was preserved. The anticancer activity of PEC-CCM conjugates was quantified by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay using a hepatic cancer cell line (HepG2), a breast cancer cell line (MCF-7), a cervical cancer cell line (HeLa), and a human normal kidney cell line (293A). It was found that the curcumin of PEC-CCM conjugates had a more significant inhibitory effect on cancer cells and was less cytotoxic to normal cells than free curcumin was. PEC-CCM conjugates have great potential for some food and pharmaceutical applications.

  13. New pyrimidine based ligand capped gold and platinum nano particles: Synthesis, characterization, antimicrobial, antioxidant, DNA interaction and in vitro anticancer activities.

    Science.gov (United States)

    Sankarganesh, M; Adwin Jose, P; Dhaveethu Raja, J; Kesavan, M P; Vadivel, M; Rajesh, J; Jeyamurugan, R; Senthil Kumar, R; Karthikeyan, S

    2017-11-01

    In this research work, we have synthesized new pyrimidine based Schiff base ligand, 2-((4,6-dimethoxypyrimidine-2-yl)methyleneenamino)-6-methoxyphenol (DPMM) capped gold (Au) and platinum (Pt) nanoparticles (NPs) by modified Brust-Schiffrin method. The characteristics of DPMM-Au NPs and DPMM-Pt NPs have been examined by UV-Visible, FTIR, SEM, TEM and powder XRD analysis. SEM analysis result shows that surface morphology of the DPMM-Au NPs and DPMM-Pt NPs are in granular and spherical shape, correspondingly. The size of the DPMM-Au NPs and DPMM-Pt NPs are approximately 38.14±4.5 and 58.64±3.0nm respectively, which confirmed by TEM analysis. The DPMM-Au NPs and DPMM-Pt NPs have potent antimicrobial against Escherichia coli, Klebsiella pneumonia, Pseudomonas fluorescens, Shigella sonnei, Staphylococcus aureus and Aspergillus niger, Candida albicans, Candida tropicalis, Mucor indicus, Rhizopus strains. The DPMM-Au NPs and DPMM-Pt NPs have good antioxidant activities than the free ligand (DPMM). The spectroscopic and viscometric measurement confirms the hydrophobic DNA binding abilities of the newly prepared DPMM capped metal NPs. Moreover, the in vitro anticancer activity of DPMM, DPMM-Au NPs and DPMM-Pt NPs against cancer (MCF-7, HeLa & HEp2) and normal (NHDF) cell lines have performed using MTT assay. These results reveals that, DPMM-Au NPs and DPMM-Pt NPs having significant cytotoxic activity against the cancer cell lines and least toxic effect on normal cell line as compared to standard drug cisplatin. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Experimental therapy of ovarian cancer with synthetic makaluvamine analog: in vitro and in vivo anticancer activity and molecular mechanisms of action.

    Directory of Open Access Journals (Sweden)

    Tao Chen

    Full Text Available The present study was designed to determine the biological effects of novel marine alkaloid analog 7-(4-fluorobenzylamino-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H-one (FBA-TPQ on human ovarian cancer cells for its anti-tumor potential and the underlying mechanisms as a novel chemotherapeutic agent. Human ovarian cancer cells (A2780 and OVCAR-3, and Immortalized non-tumorigenic human Ovarian Surface Epithelial cells (IOSE-144, were exposed to FBA-TPQ for initial cytotoxicity evaluation (via MTS assay kit, Promega. The detailed in-vitro (cell level and in-vivo (animal model studies on the antitumor effects and possible underlying mechanisms of action of the compounds were then performed. FBA-TPQ exerted potent cytotoxicity against human ovarian cancer A2780 and OVCAR-3 cells as an effective inhibitor of cell growth and proliferation, while exerting lesser effects on non-tumorigenic IOSE-144 cells. Further study in the more sensitive OVCAR-3 cell line showed that it could potently induce cell apoptosis (Annexin V-FITC assay, G2/M cell cycle arrest (PI staining analysis and also dose-dependently inhibit OVCAR-3 xenograft tumors' growth on female athymic nude mice (BALB/c, nu/nu. Mechanistic studies (both in vitro and in vivo revealed that FBA-TPQ might exert its activity through Reactive Oxygen Species (ROS-associated activation of the death receptor, p53-MDM2, and PI3K-Akt pathways in OVCAR-3 cells, which is in accordance with in vitro microarray (Human genome microarrays, Agilent data analysis (GEO accession number: GSE25317. In conclusion, FBA-TPQ exhibits significant anticancer activity against ovarian cancer cells, with minimal toxicity to non-tumorigenic human IOSE-144 cells, indicating that it may be a potential therapeutic agent for ovarian cancer.

  15. Current situation and future usage of anticancer drug databases.

    Science.gov (United States)

    Wang, Hongzhi; Yin, Yuanyuan; Wang, Peiqi; Xiong, Chenyu; Huang, Lingyu; Li, Sijia; Li, Xinyi; Fu, Leilei

    2016-07-01

    Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.

  16. Synthesis of 3-(4, 5-dihydro-1-phenyl-5-substituted phenyl-1H-pyrazol-3-yl-2H-chromen-2-one derivatives and evaluation of their anticancer activity

    Directory of Open Access Journals (Sweden)

    Nitin Kumar

    2017-05-01

    Full Text Available A novel series of 3-(4, 5-dihydro-1-phenyl-5-substituted phenyl-1H-pyrazol-3-yl-2H-chromen-2-one derivatives were synthesized. In the first step salicylaldehyde was reacted with ethylacetoacetate at room temperature by stirring which gives compound (I. Compound (I when refluxed with substituted benzaldehyde and diethylamine in the presence of n-butanol for 4–5 h gives substituted derivatives (IIa–d. Compounds synthesized in step 2 when refluxed with phenyl hydrazine in the presence of pyridine for 6–7 h gives the title compounds (IIIa–d. All the synthesized compounds were sent to NCI for anticancer activity. Synthesized compounds were tested for anticancer activity against 60 different cell lines. From the data thus obtained it was observed that simple coumarin ring derivatives were more effective in inhibiting the growth of cancerous cell lines, than coumarin-pyrazoline derivatives. Among all the synthesized compounds, irrespective of compounds having simple coumarin ring and coumarin-pyrazoline combination, compounds IIa–c, IIIb and IIId were potent anticancer agents. Compounds were active for the single dose therapeutic program at the dose of 1.00E-5 molar concentration. The main anti cancer activity is assumed to be due to the presence of the lactone structure in coumarin moiety.

  17. Circulating TFH subset distribution is strongly affected in lupus patients with an active disease.

    Directory of Open Access Journals (Sweden)

    Carole Le Coz

    Full Text Available Follicular helper T cells (TFH represent a distinct subset of CD4(+ T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-CCR6(+, TFH1 (CXCR3 (+ CCR6(- or TFH2 (CXCR3(-CCR6(- cells among CXCR5 (+ CD45RA(-CD4(+ T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI score>8, while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-IgD(-CD19(+ cells expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.

  18. Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

    Science.gov (United States)

    Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

    2014-09-01

    Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

  19. p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Cappadone, C., E-mail: concettina.cappadone@unibo.it [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Stefanelli, C. [Department for Life Quality Studies, University of Bologna, Rimini Campus, Rimini (Italy); Malucelli, E. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Zini, M. [Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna (Italy); Onofrillo, C. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Locatelli, A.; Rambaldi, M.; Sargenti, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Merolle, L. [ELETTRA–Sincrotrone Trieste S.C.p.A., Trieste (Italy); Farruggia, G. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy); Graziadio, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Montanaro, L. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Iotti, S. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy)

    2015-11-13

    Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

  20. Antioxidant activity and chemical components as potential anticancer agents in the olive leaf (Olea europaea L. cv Leccino.) decoction.

    Science.gov (United States)

    De Marino, Simona; Festa, Carmen; Zollo, Franco; Nini, Antonella; Antenucci, Lina; Raimo, Gennaro; Iorizzi, Maria

    2014-01-01

    Epidemiological studies have shown that a reduced risk of chronic diseases such as cancer and cardiovascular diseases is correlated with a regular consumption of fruits and vegetable, many of which are rich in polyphenols. The additive and synergistic effect of phytochemicals in fruits and vegetables may reduce chronic diseases related to oxidative stress in human body. Olea europaea L. leaf are rich in phenolic components, which have been proposed to play a role in cancer prevention. The purpose of this study was to identify the main components in the Olea europaea L. leaf (cv. Leccino) preserved during the decoction preparation, in order to delineate the antioxidant activities of the crude extracts and its isolated compounds by using different in vitro assays including DPPH radicalscavenging capacity, total antioxidant capacity (TAC), xanthine oxidase (XO) inhibitory effect and the ability to delay the linoleic acid peroxidation process (ALP). The aqueous decoction was partitioned obtaining four extracts and the n-butanol extract showed the highest antioxidant activity and the highest total phenolic content. Phytochemical investigation leads to the isolation of thirteen secondary metabolites including simple phenolics, flavonoids, secoiridoids whose structures were elucidated by spectroscopic data (1D and 2D NMR) and spectrometric techniques. A significant free radical scavenging effect against DPPH has been evidenced in fraxamoside (1) (EC50 62.6 µM) and taxifolin (5) (EC50 50.0 µM), isolated for the first time from the water decoction. The most active compound in the TAC evaluation, was the 3,4 dihydro-phenyl glycol (8) (0.90 caffeic acid equiv.) while taxifolin and fraxamoside resulted as the most efficient inhibitors of XO activity (IC50 2.7 and 5.2 µM, respectively). Secoxyloganin (4), oleuropein (2) and tyrosol (6) showed the highest ALP activity. This study adds to the growing body of data supporting the bioactivities of phytochemicals and their

  1. p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

    International Nuclear Information System (INIS)

    Cappadone, C.; Stefanelli, C.; Malucelli, E.; Zini, M.; Onofrillo, C.; Locatelli, A.; Rambaldi, M.; Sargenti, A.; Merolle, L.; Farruggia, G.; Graziadio, A.; Montanaro, L.; Iotti, S.

    2015-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

  2. Evaluation of In Vitro Anticancer Activity of Ocimum Basilicum, Alhagi Maurorum, Calendula Officinalis and Their Parasite Cuscuta Campestris

    OpenAIRE

    Behbahani, Mandana

    2014-01-01

    The present investigation was carried out to study the relationship between presence of cytotoxic compounds in Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris. The cytotoxic activity of the pure compounds was performed by MTT assay against breast cancer cell lines (MCF-7 and MDA-MB-231) and normal breast cell line (MCF 10A). The induction of apoptosis was measured by the expression levels of p53, bcl-2, bax and caspase-3 genes using quantitative ...

  3. Synthesis and Anticancer Activity of Some New Pyrazolo[3,4-d]pyrimidin-4-one Derivatives

    Directory of Open Access Journals (Sweden)

    Khaled R. A. Abdellatif

    2014-03-01

    Full Text Available 3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d][1,3]oxazin-4-one (3 was prepared by hydrolysis of ethyl 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate (1 to afford the corresponding carboxylic acid 2, which was reacted with acetic anhydride to give 3. The pyrazolo[3,4-d][1,3]oxazin-4-one 3 was reacted with hydroxylamine hydrochloride, urea, thiourea, thiosemicarbazide, phenylhydrazine and aromatic amines to afford the corresponding pyrazolo[3,4-d]pyrimidin-4-ones 4, 5a,b, 6, 7, 8a–e, respectively. Condensation of pyrazoloxazine derivative 3 with 99% hydrazine hydrate afforded the 5-aminopyrazolo[3,4-d] pyrimidine derivative 9. Coupling of 9 with aromatic aldehydes yielded a series of 3,6-dimethyl-5-(4-substitutedbenzylideneamino-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin- 4-ones 10a–e. The new compounds were tested for their antitumor activity on the MCF-7 human breast adenocarcinoma cell line. Almost all the tested compounds revealed antitumor activity, especially 3,6-dimethyl-5-(4-nitrobenzylideneamino-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one (10e which displayed the most potent inhibitory activity with a half maximal inhibitory concentration (IC50 of 11 µM.

  4. Evaluation of in vitro anticancer activity of Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris.

    Science.gov (United States)

    Behbahani, Mandana

    2014-01-01

    The present investigation was carried out to study the relationship between presence of cytotoxic compounds in Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris. The cytotoxic activity of the pure compounds was performed by MTT assay against breast cancer cell lines (MCF-7 and MDA-MB-231) and normal breast cell line (MCF 10A). The induction of apoptosis was measured by the expression levels of p53, bcl-2, bax and caspase-3 genes using quantitative Real Time PCR. Three active fractions were detected by nuclear magnetic resonance as lutein, lupeol and eugenol, respectively, in C. officinalis, A. maurorum and O. basilicum. These compounds and their epoxidized forms were also detected in their parasite C. campestris. The cytotoxic activity of lutein epoxide, lupeol epoxide and eugenol epoxide was significantly more than lutein, lupeol and eugenol. The mRNA expression level of p53, caspase-3 and bax genes were increased in both cancer cells treated with all pure compounds. However, bcl-2 gene expression decreased in treated breast cancer cells. In conclusion, all the data indicated that the epoxide forms of lupeol, lutein and eugenol are potential drug candidates for inducing apoptosis in human breast cancer cells.

  5. Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor

    Directory of Open Access Journals (Sweden)

    Laetitia Nivelle

    2017-03-01

    Full Text Available In the present study, resveratrol and various oligomeric derivatives were obtained from a 14 L bioreactor culture of elicited grapevine cell suspensions (Vitis labrusca L.. The crude ethyl acetate stilbene extract obtained from the culture medium was fractionated by centrifugal partition chromatography (CPC using a gradient elution method and the major stilbenes contained in the fractions were subsequently identified by using a 13C-NMR-based dereplication procedure and further 2D NMR analyses including HSQC, HMBC, and COSY. Beside δ-viniferin (2, leachianol F (4 and G (4′, four stilbenes (resveratrol (1, ε-viniferin (5, pallidol (3 and a newly characterized dimer (6 were recovered as pure compounds in sufficient amounts to allow assessment of their biological activity on the cell growth of three different cell lines, including two human skin malignant melanoma cancer cell lines (HT-144 and SKMEL-28 and a healthy human dermal fibroblast HDF line. Among the dimers obtained in this study, the newly characterized resveratrol dimer (6 has never been described in nature and its biological potential was evaluated here for the first time. ε-viniferin as well as dimer (6 showed IC50 values on the three tested cell lines lower than the ones exerted by resveratrol and pallidol. However, activities of the first two compounds were significantly decreased in the presence of fetal bovine serum although that of resveratrol and pallidol was not. The differential tumor activity exerted by resveratrol on healthy and cancer lines was also discussed.

  6. Evaluation of Anticancer and Antioxidant Activity of a Commercially Available CO2 Supercritical Extract of Old Man's Beard (Usnea barbata.

    Directory of Open Access Journals (Sweden)

    Ana Zugic

    Full Text Available There is a worldwide ongoing investigation for novel natural constituents with cytotoxic and antioxidant properties. The aim of this study was to investigate chemical profile and stated biological activities of the supercritical CO2 extract (SCE of old man's beard compared to the extracts obtained using the conventional techniques (Soxhlet extracts and macerate. The most abundant compound identified was usnic acid, which content was inversely proportional to the polarity of the solvent used and was the highest in the SCE, which was the sample revealing the highest cytotoxic activity in tested tumor cell lines (B16 mouse melanoma and C6 rat glioma, with lower IC50 values compared to pure usnic acid. Further investigations suggested both SCE and usnic acid to induce apoptosis and/or autophagy in B16 and C6, indicating higher cytotoxicity of SCE to be related to the higher degree of ROS production. A good correlation of usnic acid content in the extracts and their antioxidant capacity was established, extricating SCE as the most active one. Presented results support further investigations of SCE of old man's beard as a prospective therapeutic agent with potential relevance in the treatment of cancer and/or in oxidative stress-mediated conditions.

  7. Evaluation of in vitro anticancer activity of Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris.

    Directory of Open Access Journals (Sweden)

    Mandana Behbahani

    Full Text Available The present investigation was carried out to study the relationship between presence of cytotoxic compounds in Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris. The cytotoxic activity of the pure compounds was performed by MTT assay against breast cancer cell lines (MCF-7 and MDA-MB-231 and normal breast cell line (MCF 10A. The induction of apoptosis was measured by the expression levels of p53, bcl-2, bax and caspase-3 genes using quantitative Real Time PCR. Three active fractions were detected by nuclear magnetic resonance as lutein, lupeol and eugenol, respectively, in C. officinalis, A. maurorum and O. basilicum. These compounds and their epoxidized forms were also detected in their parasite C. campestris. The cytotoxic activity of lutein epoxide, lupeol epoxide and eugenol epoxide was significantly more than lutein, lupeol and eugenol. The mRNA expression level of p53, caspase-3 and bax genes were increased in both cancer cells treated with all pure compounds. However, bcl-2 gene expression decreased in treated breast cancer cells. In conclusion, all the data indicated that the epoxide forms of lupeol, lutein and eugenol are potential drug candidates for inducing apoptosis in human breast cancer cells.

  8. New 15-membered tetraaza (N4) macrocyclic ligand and its transition metal complexes: Spectral, magnetic, thermal and anticancer activity

    Science.gov (United States)

    El-Boraey, Hanaa A.; EL-Gammal, Ohyla A.

    2015-03-01

    Novel tetraamidemacrocyclic 15-membered ligand [L] i.e. naphthyl-dibenzo[1,5,9,12]tetraazacyclopentadecine-6,10,11,15-tetraoneand its transition metal complexes with Fe(II), Co(II), Ni(II), Cu(II), Ru(III) and Pd(II) have been synthesized and characterized by elemental analysis, spectral, thermal as well as magnetic and molar conductivity measurements. On the basis of analytical, spectral (IR, MS, UV-Vis, 1H NMR and EPR) and thermal studies distorted octahedral or square planar geometry has been proposed for the complexes. The antitumor activity of the synthesized ligand and some complexes against human breast cancer cell lines (MCF-7) and human hepatocarcinoma cell lines (HepG2) has been studied. The complexes (IC50 = 2.27-2.7, 8.33-31.1 μg/mL, respectively) showed potent antitumor activity, towards the former cell lines comparable with their ligand (IC50 = 13, 26 μg/mL, respectively). The results show that the activity of the ligand towards breast cancer cell line becomes more pronounced and significant when coordinated to the metal ion.

  9. Curcumin loaded poly(2-hydroxyethyl methacrylate) nanoparticles from gelled ionic liquid--in vitro cytotoxicity and anti-cancer activity in SKOV-3 cells.

    Science.gov (United States)

    Kumar, Sathish Sundar Dhilip; Surianarayanan, Mahadevan; Vijayaraghavan, R; Mandal, Asit Baran; MacFarlane, D R

    2014-01-23

    The main focus of this study is to encapsulate hydrophobic drug curcumin in hydrophilic polymeric core such as poly(2-hydroxyethyl methacrylate) [PHEMA] nanoparticles from gelled ionic liquid (IL) to improve its efficacy. We have achieved 26.4% drug loading in a biocompatible hydrophilic polymer. Curcumin loaded PHEMA nanoparticles (C-PHEMA-NPs) were prepared by nano-precipitation method. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were spherical in shape and free from aggregation. The size and zeta potential of prepared C-PHEMA-NPs were about 300 nm and -33.4 mV respectively. C-PHEMA-NPs were further characterized by FT-IR spectroscopy which confirmed the existence of curcumin in the nanoparticles. X-ray diffraction and differential scanning calorimetry studies revealed that curcumin present in the PHEMA nanoparticles were found to be amorphous in nature. The anticancer activity of C-PHEMA-NPs was measured in ovarian cancer cells (SKOV-3) in vitro, and the results revealed that the C-PHEMA-NPs had better tumor cells regression activity than free curcumin. Flow cytometry showed the significant reduction in G0/G1 cells after treatment with C-PHEMA-NPs and molecular level of apoptosis were also studied using western blotting. Toxicity of PHEMA nanoparticles were studied in zebrafish embryo model and results revealed the material to be highly biocompatible. The present study demonstrates the curcumin loaded PHEMA nanoparticles have potential therapeutic values in the treatment of cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Synthesis, structural characterization, in vitro antimicrobial and anticancer activity studies of ternary metal complexes containing glycine amino acid and the anti-inflammatory drug lornoxicam

    Science.gov (United States)

    Mahmoud, Walaa H.; Mohamed, Gehad G.; El-Dessouky, Maher M. I.

    2015-02-01

    Mixed ligand complexes were synthesized using lornoxicam (LOR) as the primary ligand and glycine amino acid (HGly) as the secondary ligand. They were characterized by FT-IR, UV-Vis, mass, 1H NMR, ESR spectral studies, TG-DTG, X-ray powder diffraction and physical analytical studies. From the molar conductance, magnetic moment and electronic spectral data of the synthesized complexes, general formulae of [M(LOR)2(Gly)]·Xn·yH2O where M = Cr(III) (X = Cl, n = 2, y = 3), Mn(II) (X = Cl, n = 1, y = 1), Co(II) (X = BF4, n = 1, y = 0), Ni(II) (X = Cl, n = 1, y = 0), Cu(II) (X = BF4, n = 1, y = 2) and Zn(II) (X = BF4, n = 1, y = 2) and (M = Fe(II) (X = BF4, n = 1, y = 1) and Fe(III) (X = Cl, n = 2, y = 1) with an octahedral structure were proposed. Thermal analyses show that the complexes lose water molecules of hydration initially and subsequently expel anionic parts and organic ligands in continuous steps. The kinetic parameters namely E, ΔH∗, ΔS∗ and ΔG∗ illustrate the spontaneous association of the metal and ligands in the formation of the complexes. The antimicrobial efficiency of the LOR and HGly ligands and the ternary complexes were examined by in vitro method against various pathogenic bacterial and fungal strains. The metal complexes were found to possess efficient antimicrobial properties compared to lornoxicam and most of these complexes could turn out to be excellent models for the design of effective antibiotic drug substances. Also, the two ligands, in comparison to ternary metal complexes are screened for their anticancer activity against breastic cancer cell line. The results showed that the metal complexes be more active than the parent LOR and glycine free ligands except Cr(III) ternary complex which was found to be inactive.

  11. Enhanced oral bioavailability and anticancer activity of novel curcumin loaded mixed micelles in human lung cancer cells.

    Science.gov (United States)

    Patil, Sharvil; Choudhary, Bhavana; Rathore, Atul; Roy, Krishtey; Mahadik, Kakasaheb

    2015-11-15

    Curcumin has a wide range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antibacterial, wound healing, antiatherosclerotic, hepatoprotective and anti-carcinogenic. However, its clinical applications are limited owing to its poor aqueous solubility, multidrug pump P-gp efflux, extensive in vivo metabolism and rapid elimination due to glucuronidation/sulfation. The objective of the current work was to prepare novel curcumin loaded mixed micelles (CUR-MM) of Pluronic F-127 (PF127) and Gelucire® 44/14 (GL44) in order to enhance its oral bioavailability and cytotoxicity in human lung cancer cell line A549. 3(2) Factorial design was used to assess the effect of formulation variables for optimization of mixed micelle batch. CUR-MM was prepared by a solvent evaporation method. The optimized CUR-MM was evaluated for size, entrapment efficiency (EE), in vitro curcumin release, cytotoxicity and oral bioavailability in rats. The average size of CUR-MM was found to be around 188 ± 3 nm with an EE of about 76.45 ± 1.18% w/w. In vitro dissolution profile of CUR-MM revealed controlled release of curcumin. Additionally, CUR-MM showed significant improvement in cytotoxic activity (3-folds) and oral bioavailability (around 55-folds) of curcumin as compared to curcumin alone. Such significant improvement in cytotoxic activity and oral bioavailability of curcumin when formulated into mixed micelles could be attributed to solubilization of hydrophobic curcumin into micelle core along with P-gp inhibition effect of both, PF127 and GL44. Thus the present work propose the formulation of mixed micelles of PF127 and GL44 which can act as promising carrier systems for hydrophobic drugs such as curcumin with significant improvement in their oral bioavailability. Copyright © 2015 Elsevier GmbH. All rights reserved.

  12. Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

    Science.gov (United States)

    Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

    2017-12-01

    Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

  13. A novel antibody-drug conjugate anti-CD19(Fab)-LDM in the treatment of B-cell non-Hodgkin lymphoma xenografts with enhanced anticancer activity.

    Science.gov (United States)

    Jiang, Linlin; Yang, Ming; Zhang, Xiaoyun; Bao, Shiqi; Ma, Li; Fan, Dongmei; Zhou, Yuan; Xiong, Dongsheng; Zhen, Yongsu

    2016-01-01

    Rituximab is widely used in clinical setting for the treatment of B malignant lymphoma and has achieved remarkable success. However, in most patients, the disease ultimately relapses and become resistant to rituximab. To overcome the limitation, there is still a need to find novel strategy for improving therapeutic efficacy. To construct genetically engineered antibody anti-CD19(Fab)-LDM, and verify the anticancer activity targeted toward B-lymphoma. The anticancer activity of anti-CD19(Fab)-LDM in vitro and in vivo was examined. In vitro, the binding activity and internalization of anti-CD19(Fab)-LDP were measured. Using comet assay and apoptosis, the cytotoxicity of energized fusion proteins was observed. From in vivo experiments, targeting of therapeutic effect and anticancer efficacy bythe fusion protein was verified. Data showed that anti-CD19(Fab)-LDM does not only binding the cell surface but is also internalized into the cell. The energized fusion proteins anti-CD19(Fab)-LDM can induce DNA damage. Furthermore, significant in vivo therapeutic efficacy was observed. The present study demonstrated that the genetically engineered antibody anti-CD19(Fab)-LDM exhibited enhanced cytotoxicity compared to LDM alone. One of the most powerful advantages of anti-CD19(Fab)-LDM, however, is that it can be internalized within the cells and carry out cytotoxic effects. Therefore, anti-CD19(Fab)-LDM may be as a useful targeted therapy for B-cell lymphoma.

  14. Biotransformation of 20(S)-protopanaxatriol by Mucor racemosus and the anti-cancer activities of some products.

    Science.gov (United States)

    Chen, Guangtong; Ge, Hongjuan; Song, Yan; Li, Jianlin; Zhai, Xuguang; Wu, Juanjuan; Ling, Xiang

    2015-10-01

    To produce new derivatives of 20(S)-protopanaxatriol by fungal biotransformation. Biotransformation of 20(S)-protopanaxatriol (1) by Mucor racemosus AS 3.205 afforded six products. Their structures were elucidated on the basis of extensive spectroscopic analyses. M. racemosus could selectively catalyze dehydrogenation at C-12 and further hydroxylation at C-7, C-11, and C-15, as well as rearrangement of double bond at C-26. Two of these new compounds exhibited potent inhibitory activity against SH-SY5Y and HepG2 cell lines. Biotransformation by M. racemosus AS 3.205 was an effective approach to produce new derivatives of 20(S)-protopanaxatriol.

  15. Potential Anticancer Properties of Grape Antioxidants

    Directory of Open Access Journals (Sweden)

    Kequan Zhou

    2012-01-01

    Full Text Available Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera, one of the world’s largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted.

  16. Synthesis, crystal structure and anticancer activity of tetrakis(N-isopropylimidazolidine-2-selenone)platinum(II) chloride

    Science.gov (United States)

    Ahmad, Saeed; Altoum, Ali Osman S.; Vančo, Ján; Křikavová, Radka; Trávníček, Zdeněk; Dvořák, Zdeněk; Altaf, Muhammad; Sohail, Manzar; Isab, Anvarhusein A.

    2018-01-01

    A Platinum(II) complex of N-isopropylimidazolidine-2-selenone (i-PrImSe), [Pt(i-PrImSe)4]Cl2 (1) was prepared and characterized by elemental analysis, IR and NMR (1H, 13C, 77Se &195Pt) spectroscopy, and X-ray crystallography. The structure of 1 consists of [Pt(i-PrImSe)4]2+ complex ion and chloride counter ions. The platinum(II) atom adopts a distorted square planar geometry. The in vitro antitumor activity of 1 as well as cisplatin, was evaluated by MTT assay against human; ovarian carcinoma A2780 and its cisplatin-resistant subline A2780R, prostate cancer 22Rv1 and breast cancer MCF-7 cell lines. The title complex displayed the activity against the A2780 cells (IC50 = 30.8 μM) at the level comparable to cisplatin (IC50 = 26.8 μM). The interaction studies with sulfur-containing biomolecules revealed its ability to form a variety of intermediates and oxidized species with L-cysteine and reduced glutathione.

  17. Phytochemical screening, anticancer and antioxidant activities of Origanum vulgare L. ssp. viride (Boiss.) Hayek, a plant of traditional usage.

    Science.gov (United States)

    Koldaş, Serkan; Demirtas, Ibrahim; Ozen, Tevfik; Demirci, Mehmet Ali; Behçet, Lütfi

    2015-03-15

    A detailed phytochemical analysis of Origanum vulgare L. ssp. viride (Boiss.) Hayek was carried out and the antioxidant activities of five different crude extracts were determined. The antiproliferative activities of the extracts were determined using the xCELLigence system (Real Time Cell Analyzer). Differences between the essential oil and volatile organic compound profiles of the plant were shown. The main component of the essential oil was caryophyllene oxide, while the main volatile organic compounds were sabinene and eucalyptol as determined by HS-GC/MS. Phenolic contents of the extracts were determined qualitatively and quantitatively by HPLC/TOF-MS. Ten phenolic compounds were found in the extracts from O. vulgare and Origanum acutidens: rosmarinic acid (in highest abundance), chicoric acid, caffeic acid, p-coumaric acid, gallic acid, quercetin, apigenin-7-glucoside, kaempferol, naringenin and 4-hydroxybenzaldehyde. This study provides first results on the antiproliferative and antioxidant properties and detailed phytochemical screening of O. vulgare ssp. viride (Boiss.) Hayek. © 2014 Society of Chemical Industry.

  18. Epigenetic Activity of Peroxisome Proliferator-Activated Receptor Gamma Agonists Increases the Anticancer Effect of Histone Deacetylase Inhibitors on Multiple Myeloma Cells.

    Directory of Open Access Journals (Sweden)

    Nassera Aouali

    Full Text Available Epigenetic modifications play a major role in the development of multiple myeloma. We have previously reported that the PPARγ agonist pioglitazone (PIO enhances, in-vitro, the cytotoxic effect of the Histone deacetylase inhibitor (HDACi, valproic acid (VPA, on multiple myeloma cells. Here, we described the development of a new multiple myeloma mouse model using MOLP8 cells, in order to evaluate the effect of VPA/PIO combination on the progression of myeloma cells, by analyzing the proliferation of bone marrow plasma cells. We showed that VPA/PIO delays the progression of the disease and the invasion of myeloma cells in the bone marrow. Mechanistically, we demonstrated that VPA/PIO increases the cleavage of caspase 3 and PARP, and induces the acetylation of Histone 3 (H3. Furthermore, we provided evidence that PPARγ agonist is able to enhance the action of other HDACi such as Vorinostat or Mocetinostat. Using PPARγ antagonist or siPPARγ, we strongly suggest that, as described during adipogenesis, PIO behaves as an epigenetic regulator by improving the activity of HDACi. This study highlights the therapeutic benefit of PIO/VPA combination, compared to VPA treatment as a single-arm therapy on multiple myeloma and further highlights that such combination may constitute a new promising treatment strategy which should be supported by clinical trials.

  19. Anticancer Drugs from Marine Flora: An Overview

    OpenAIRE

    Sithranga Boopathy, N.; Kathiresan, K.

    2010-01-01

    Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharide...

  20. Anticancer Properties of Lamellarins

    Directory of Open Access Journals (Sweden)

    Christian Bailly

    2015-02-01

    Full Text Available In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids.

  1. Lupane-type triterpenes and their anti-cancer activities against most common malignant tumors: A review

    Science.gov (United States)

    Cháirez-Ramírez, MH; Moreno-Jiménez, MR; González-Laredo, RF; Gallegos-Infante, JA; Rocha-Guzmán, Nuria Elizabeth

    2016-01-01

    In recent times, a great deal of interest has been motivated on plant derived compounds known as nutraceuticals. These compounds exert important beneficial activities that improve people's health status when are consumed regularly, and now they appear as a viable option to explore their possible therapeutic effects against diseases like cancer. Particularly, lupane-type triterpenes have shown great ability to modulate multiple cancer-related signaling pathways and processes, including NF-κB, Wnt/β-catenin, PI3K/Akt, apoptosis, and many other routes related to proliferation or cell death, which are uncontrolled in malignant tumors. These investigations have promoted in vitro and in vivo studies, searching their mechanisms of action; although more research is still needed to prove its potential in human clinical trials. This review focuses on the ability of betulin, betulinic acid and lupeol to show benefits against the most common types of malignant tumors, which are considered a major global threat for public health. PMID:28337107

  2. Increases in Phenolic, Fatty Acid, and Phytosterol Contents and Anticancer Activities of Sweet Potato after Fermentation by Lactobacillus acidophilus.

    Science.gov (United States)

    Shen, Yixiao; Sun, Haiyan; Zeng, Haiying; Prinyawiwatukul, Witoon; Xu, Wenqing; Xu, Zhimin

    2018-03-21

    Phenolic, fatty acid, and phytosterol contents in sweet potato (SP) fermented by Lactobacillus acidophilus were evaluated and compared with those of raw and boiled SPs. The differences in the profiles and levels of phenolics between the raw and boiled SPs were not as significant as the differences between those and the fermented SP. The levels of caffeic acid and 3,5-dicaffeoylquinic acid in fermented SP were more than 4 times higher than those in raw and boiled SPs. Two phenolics, p-coumaric acid and ferulic acid, which were not detected in either raw or boiled SP, were found in fermented SP. The level of each fatty acid or phytosterol increased in fermented SP and decreased in boiled SP. Among the hydrophilic and lipophilic extracts obtained from raw and fermented SPs, the hydrophilic extract of fermented SP exhibited the highest capability of inhibiting cancer-cell PC-12 proliferation. However, each of the extracts had very low cytotoxicities to normal-monkey-kidney-cell growth. The results indicated that SP fermented by L. acidophilus significantly increased free antioxidant-rich phenolics and inhibited cancer-cell-proliferation activity without cytotoxicity to normal cells.

  3. Ibuprofen enhances the ant