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Sample records for cell lines antiproliferative

  1. Antiproliferative effect of isopentenylated coumarins on several cancer cell lines.

    Science.gov (United States)

    Kawaii, S; Tomono, Y; Ogawa, K; Sugiura, M; Yano, M; Yoshizawa, Y; Ito, C; Furukawa, H

    2001-01-01

    33 coumarins, mainly the simple isopentenylated coumarins and derived pyrano- and furanocoumarins, were examined for their antiproliferative activity towards several cancer and normal human cell lines. The pyrano- and furanocoumarins showed strong activity against the cancer cell lines, whereas they had weak antiproliferative activity against the normal human cell lines. The decreasing rank order of potency was osthenone (10), clausarin (25), clausenidin (26), dentatin (24), nordentatin (23), imperatorin (29), seselin (27), xanthyletin (21), suberosin (17), phebalosin (8) and osthol (12). The structure-activity relationship established from the results revealed that the 1,1-dimethylallyl and isopentenyl groups have an important role for antiproliferative activity. PMID:11497276

  2. Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines

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    Ismail Noorliza M

    2010-09-01

    Full Text Available Abstract Background The treatment of oral squamous cell carcinomas (OSCC and human osteosarcoma (HOS includes surgery and/or radiotherapy which often lead to reduced quality of life. This study was aimed to study the antiproliferative activity of local honey (Tualang on OSCC and HOS cell lines. Methods Several concentrations of Tualang honey (1% - 20% were applied on OSCC and HOS cell lines for 3, 6, 12, 24, 48 and 72 hours. Morphological characteristics were observed under light and fluorescent microscope. Cell viability was assessed using MTT assay and the optical density for absorbance values in each experiment was measured at 570 nm by an ELISA reader. Detection of cellular apoptosis was done using the Annexin V-FITC Apoptosis Detection Kit. Results Morphological appearance showed apoptotic cellular changes like becoming rounded, reduction in cell number, blebbed membrane and apoptotic nuclear changes like nuclear shrinkage, chromatin condensation and fragmented nucleus on OSCC and HOS cell lines. Cell viability assay showed a time and dose-dependent inhibitory effect of honey on both cell lines. The 50% inhibitory concentration (IC50 for OSCC and HOS cell lines was found to be 4% and 3.5% respectively. The maximum inhibition of cell growth of ≥80% was obtained at 15% for both cell lines. Early apoptosis was evident by flow cytometry where percentage of early apoptotic cells increased in dose and time dependent manner. Conclusion Tualang honey showed antiproliferative effect on OSCC and HOS cell lines by inducing early apoptosis.

  3. Boldine: a potential new antiproliferative drug against glioma cell lines.

    Science.gov (United States)

    Gerhardt, Daniéli; Horn, Ana Paula; Gaelzer, Mariana Maier; Frozza, Rudimar Luiz; Delgado-Cañedo, Andrés; Pelegrini, Alessandra Luiza; Henriques, Amélia T; Lenz, Guido; Salbego, Christianne

    2009-12-01

    Malignant gliomas are the most common and devastating primary tumors of the central nervous system. Currently no efficient treatment is available. This study evaluated the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on glioma proliferation and cell death. Boldine decreased the cell number of U138-MG, U87-MG and C6 glioma lines at concentrations of 80, 250 and 500 muM. We observed that cell death caused by boldine was cell-type specific and dose-dependent. Exposure to boldine for 24 h did not activate key mediators of apoptosis. However, it induced alterations in the cell cycle suggesting a G(2)/M arrest in U138-MG cells. Boldine had no toxic effect on non-tumor cells when used at the same concentrations as those used on tumor cells. Based on these results, we speculate that boldine may be a promising compound for evaluation as an anti-cancer agent. PMID:19050827

  4. Clinacanthus nutans Extracts Are Antioxidant with Antiproliferative Effect on Cultured Human Cancer Cell Lines

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    Yoke Keong Yong

    2013-01-01

    Full Text Available Clinacanthus nutans Lindau leaves (CN have been used in traditional medicine but the therapeutic potential has not been explored for cancer prevention and treatment. Current study aimed to evaluate the antioxidant and antiproliferative effects of CN, extracted in chloroform, methanol, and water, on cancer cell lines. Antioxidant properties of CN were evaluated using DPPH, galvinoxyl, nitric oxide, and hydrogen peroxide based radical scavenging assays, whereas the tumoricidal effect was tested on HepG2, IMR32, NCL-H23, SNU-1, Hela, LS-174T, K562, Raji, and IMR32 cancer cells using MTT assay. Our data showed that CN in chloroform extract was a good antioxidant against DPPH and galvinoxyl radicals, but less effective in negating nitric oxide and hydrogen peroxide radicals. Chloroform extract exerted the highest antiproliferative effect on K-562 (91.28±0.03% and Raji cell lines (88.97±1.07% at 100 μg/ml and the other five cancer cell lines in a concentration-dependent manner, but not on IMR-32 cells. Fourteen known compounds were identified in chloroform extract, which was analysed by gas chromatography—mass spectra analysis. In conclusion, CN extracts possess antioxidant and antiproliferative properties against cultured cancer cell lines, suggesting an alternate adjunctive regimen for cancer prevention or treatment.

  5. Clinacanthus nutans Extracts Are Antioxidant with Antiproliferative Effect on Cultured Human Cancer Cell Lines.

    Science.gov (United States)

    Yong, Yoke Keong; Tan, Jun Jie; Teh, Soek Sin; Mah, Siau Hui; Ee, Gwendoline Cheng Lian; Chiong, Hoe Siong; Ahmad, Zuraini

    2013-01-01

    Clinacanthus nutans Lindau leaves (CN) have been used in traditional medicine but the therapeutic potential has not been explored for cancer prevention and treatment. Current study aimed to evaluate the antioxidant and antiproliferative effects of CN, extracted in chloroform, methanol, and water, on cancer cell lines. Antioxidant properties of CN were evaluated using DPPH, galvinoxyl, nitric oxide, and hydrogen peroxide based radical scavenging assays, whereas the tumoricidal effect was tested on HepG2, IMR32, NCL-H23, SNU-1, Hela, LS-174T, K562, Raji, and IMR32 cancer cells using MTT assay. Our data showed that CN in chloroform extract was a good antioxidant against DPPH and galvinoxyl radicals, but less effective in negating nitric oxide and hydrogen peroxide radicals. Chloroform extract exerted the highest antiproliferative effect on K-562 (91.28 ± 0.03%) and Raji cell lines (88.97 ± 1.07%) at 100  μ g/ml and the other five cancer cell lines in a concentration-dependent manner, but not on IMR-32 cells. Fourteen known compounds were identified in chloroform extract, which was analysed by gas chromatography-mass spectra analysis. In conclusion, CN extracts possess antioxidant and antiproliferative properties against cultured cancer cell lines, suggesting an alternate adjunctive regimen for cancer prevention or treatment. PMID:23533485

  6. Antiproliferative effects of Ceratonia siliqua L. on mouse hepatocellular carcinoma cell line.

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    Corsi, L; Avallone, R; Cosenza, F; Farina, F; Baraldi, C; Baraldi, M

    2002-12-01

    Extracts from pods and leaves of carob (Ceratonia siliqua L.) were tested for their ability to inhibit cell proliferation of mouse hepatocellular carcinoma cell line (T1). The two extracts showed a marked alteration of T1 cell proliferation in a dose-related fashion reaching the maximal effect at 1 mg/ml. Moreover, we demonstrated that leaf and pod extracts were able to induce apoptosis in T1 cell lines after 24-h treatment mediating a direct activation of the caspase 3 pathway. HPLC analysis revealed the presence of gallic acid, (-) epigallocatechin-3-gallate and (-) epicatechin-3-gallate in pod and leaf extracts, compounds well known to exert antiproliferative effects. Their concentration reached 6.28 mg/g in carob leaves and 1.36 mg/g in carob pods extract. The discovery that carob pod and leaf extracts contained antiproliferative agents could be of practical importance in the development of functional foods and/or chemopreventive drugs.

  7. Clinacanthus nutans Extracts Are Antioxidant with Antiproliferative Effect on Cultured Human Cancer Cell Lines

    OpenAIRE

    Yoke Keong Yong; Jun Jie Tan; Soek Sin Teh; Siau Hui Mah; Gwendoline Cheng Lian Ee; Hoe Siong Chiong; Zuraini Ahmad

    2013-01-01

    Clinacanthus nutans Lindau leaves (CN) have been used in traditional medicine but the therapeutic potential has not been explored for cancer prevention and treatment. Current study aimed to evaluate the antioxidant and antiproliferative effects of CN, extracted in chloroform, methanol, and water, on cancer cell lines. Antioxidant properties of CN were evaluated using DPPH, galvinoxyl, nitric oxide, and hydrogen peroxide based radical scavenging assays, whereas the tumoricidal effect was teste...

  8. Anti-proliferative effect of Ficus pumila Linn. on human leukemic cell lines

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    Christopher Larbie

    2015-04-01

    Conclusion: These findings suggest that crude extracts of FPS and FPL have anti-proliferative effect on the leukemia cells. The antioxidant properties of the plant including phenolics may be partly responsible for the anti-proliferative activity. Further studies are required to isolate chemical components of the plant and establish their anti-proliferative activities and mechanism of action. [Int J Basic Clin Pharmacol 2015; 4(2.000: 330-336

  9. Anti-proliferative activity of Fumaria vaillantii extracts on different cancer cell lines

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    Fatemeh Haji Abbas Tabrizi

    2016-01-01

    Full Text Available Plant-derived natural products are known to have cancer chemo-preventive and chemo-therapeutic properties. Plant extracts or their active constituents are used as folk medicine in traditional therapies by 80% of the world population. The aim of the present study was to determine the anti-proliferative potential of Fumaria vaillantii extracts on three different cancer cell lines including malignant melanoma SKMEL-3, human breast adenocarcinoma MCF-7 and human myelogenous leukemia K562 as well as human gingival fibroblast (HGF as normal cell line. Anti-proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, flowcytometry and annexin methods. Total phenolics and flavonoids were determined by Folin-Ciocalteu and aluminum chloride methods. Chloroform fraction had the lowest IC 50 value at 72 h (0.1 μg/ml in MCF-7 cells. Flowcytometry and annexin-V analysis indicated that the chloroform fraction induced necrosis in MCF-7 cells. In addition, the colorimetric methods showed that the methanolic fraction possessed the highest amount of total phenolics (33.03 ± 0.75 mg/g of dry powder and flavonoids (10.5 ± 2.0 mg/g of dry powder.The collective data demonstrated that F. vaillantii chloroform fraction may contain effective compounds with chemo-therapeutic potential act through an apoptotic independent pathway.

  10. Antiproliferative effect of linalool on RPMI 7932 human melanoma cell line: ultrastructural studies.

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    Cerchiara, Teresa; Straface, Serafina Vittoria; Brunelli, Elvira; Tripepi, Sandro; Gallucci, Maria Caterina; Chidichimo, Giuseppe

    2015-04-01

    Linalool, a small monoterpene molecule, is used widely for its flavoring and fragrant properties in many cosmetic products. In this work, we investigated the antiproliferative effect of two different linalool solutions on RPMI 7932 human melanoma and NCTC 2544 normal keratinocites cell lines using the trypan blue method. Morphological changes in cells were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, apoptosis was evaluated using caspase 3-antibody. Linalool showed a selective inhibitory effect on the growth of melanoma cells in a concentrationdependent manner, inducing several morphological changes, as revealed by SEM and TEM analysis. Moreover, the labelling for caspase-3 is abundant in the melanoma cells and almost absent in the normal keratinocites cells. The results suggest that linalool could be used as drug and/or as model drug for developing potential therapeutic agents for melanoma.

  11. Antiproliferative activity of Eremanthus crotonoides extracts and centratherin demonstrated in brain tumor cell lines

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    Jonathas F. R. Lobo

    2012-12-01

    Full Text Available The genus Eremanthus is recognized by the predominance of sesquiterpene lactones from the furanoheliangolide type, a class of substances extensively tested against cancer cell lines. Thus, the species E. crotonoides (DC. Sch. Bip., Asteraceae, obtained on "restinga" vegetation was evaluated against U251 and U87-MG glioma cell lines using the MTT colorimetric assay. Dichloromethane fraction was cytotoxic to both glioblastoma multiforme cell lines. We then conducted UPLC-PDA-ESI-MS/MS analysis of the dichloromethane fraction, which allowed the identification of the sesquiterpene lactones centratherin and goyazensolide. The isolation of centratherin was performed using chromatographic techniques and the identification of this substance was confirmed according to NMR data. Cytotoxic activity of centratherin alone was also evaluated against both U251 and U87-MG cells, which showed IC50 values comparable with those obtained for the commercial anticancer drug doxorubicin. All the tested samples showed cytotoxic activity against glioblastoma multiforme cells which suggests that E. crotonoides extracts may be important sources of antiproliferative substances and that the centratherin may serve as prototype for developing new antiglioblastoma drugs.

  12. Antiproliferative, genotoxic and oxidant activities of cyclosativene in rat neuron and neuroblastoma cell lines

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    Toğar Başak

    2014-01-01

    Full Text Available Cyclosativene (CSV is a tetracyclic sesquiterpene found in the essential oils of Centaurea cineraria (Asteraceae and Abies magnifica A. Murray (Pinaceae plants. To the best of our knowledge, its cytotoxic, genotoxic and oxidant effects have never been studied on any cell lines. Therefore, we aimed to investigate the in vitro antiproliferative and/or cytotoxic properties, antioxidant/oxidant activity and genotoxic damage potential of CSV in healthy neurons and N2a neuroblastoma (N2a-NB cell cultures. After treatment with 10-400 μg/ml of CSV for 24 h, cell proliferation was measured by the MTT (3,(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. The antioxidant activity was assessed by the total antioxidant capacity (TAC and total oxidative stress (TOS assays. To evaluate the level of DNA damage, single cell gel alkaline electrophoresis (SCGE was used. The MTT assay showed that the application of CSV significantly reduced cell viability in both cell types. CSV treatments at higher doses led to decreases of TAC levels and increases of TOS levels in neuron and N2a-NB cells. The mean values of the total scores of cells showing DNA damage were not found to be significantly different from the control values in both cells. In conclusion, this study suggests that CSV has weak anticancer potential.

  13. Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

    International Nuclear Information System (INIS)

    Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobacterium adolescentis isolated from healthy young Koreans. The anti-proliferative activity of B. adolescentis isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of B. adolescentis SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line. The butanol extract of B. adolescentis SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of B. adolescentis SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells. The butanol extract of B. adolescentis SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier

  14. Antiproliferative activity of methanol extracts of four species of Croton on different human cell lines

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    Jóice P. Savietto

    2013-08-01

    Full Text Available Several species of Croton have been described with biological activities, mainly due to diterpenes, alkaloids and/or other secondary metabolites. These activities account for the traditional use of Croton species to treat certain diseases in South America, Asia and Western Africa. The crude methanol extracts obtained from leaves and steam bark of Croton dichrous Müll. Arg., C. erythroxyloides Baill., C. myrianthus Müll. Arg. and C. splendidus Mart. ex Colla were tested for antiproliferative activity against ten human cancer cell lines. Chemical analyses of all extracts were carried out by GC/MS and HPLC/MS/MS. The leaf extract obtained from C. erythroxyloides showed potent activity against PC-3 (prostate and OVCAR-3 (ovary cell lines. Lupeol is suggested to be involved in such activity. Tiliroside, an acyl-glycosilated flavonoid ubiquitous in all tested extracts, seems to play an important role in the observed moderate activity of most extracts against the leukemia K562 cell lineage.

  15. Metformin Enhances Anti-proliferative Effect of Cisplatin in Cervical Cancer Cell Line

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    Ratih D. Yudhani; Riza N. Pesik; Dono Indarto

    2016-01-01

    Cervival cancer is one of the top rank of gynecological malignancy in the world, leading to high morbidity and mortality rates. Cisplatin is a chemotherapeutic agent that is generally used to treat cervical cancer but the use of this drug is limited because of serious side effects. Metformin, a diabetic drug, decreases not only blood glucose levels but also cell viability of some cancer cells. The aim of this study was to investigate the anti-proliferative effect of combination metformin and ...

  16. Antiproliferative effects of Plumbago rosea and its purified constituent plumbagin on SK-MEL 28 melanoma cell lines

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    Anuf, Alexander Ronaldo; Ramachandran, Rajesh; Krishnasamy, Rajaram; Gandhi, P.S. Sudhakar; Periyasamy, Sureshkumar

    2014-01-01

    Background: Plumbago rosea is used in traditional systems of medicine for the preparation of formulations used for treating inflammations, cough, bronchitis, and gastrointestinal disorders, and also in conjunction with cancer chemotherapy. In the present study, the cytotoxic and anti-proliferative effects of plumbagin, and the ethanolic root extract of P. rosea (ETPR) was evaluated on SK-MEL 28 melanoma cell lines and human lymphocytes. Materials and Methods: MTT and apoptotic assays were use...

  17. Pharmacognostic standardisation and antiproliferative activity of aegle marmelos (L. Correa leaves in various human cancer cell lines

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    Rajbir Bhatti

    2013-01-01

    Full Text Available Therapeutic management of cancer is a great clinical challenge and alternative medicines are being extensively explored to have integrated approach to cure cancer. Aegle marmelos (L. Correa (Rutaceae is known for its hypoglycaemic, radioprotective, antidiarrhoeal and many other pharmacological activities. The present study is designed to carryout pharmacognostic standardisation and evaluation of antiproliferative activity of the leaf extracts Aegle marmelos (L. Correa (Rutaceae and the chromatographic fractions of the most active extract. Hexane, petroleum ether, chloroform and ethanol extracts of the shade dried leaves were prepared by soxhelation and antiproliferative activity was assessed using human cancer cell lines of lung (A-549, colon (CoLo-05, ovary (IGR-OV-1, prostrate (PC3, leukaemia (THP-1 and breast (MCF-7 cancer. Bioactivity-derived fractionation was carried out for most active extract by column chromatography. The phytochemical studies indicated alkaloids, anthraquinones, terpenoids in the alcohol, chloroform extracts and tannins, terpenoids, reducing sugars in the petroleum ether and hexane extracts. Ethanol extract showed maximum inhibition in colon and breast carcinoma cell lines at a dose of 100 μg/ml. Column chromatography of the ethanol extract yielded five fractions. Out of this, fractions 2, 4 and 5 showed significant inhibition in leukaemia cell line with IC 50 of 12.5, 86.2 and >100 μg/ml for fractions 2, 4 and 5, respectively. High-performance thin layer chromatography of the fraction 2 revealed imperatorin as one of the major phytoconstituents. Among the different extracts investigated, ethanol extract exhibited significant antiproliferative activity and its fraction 2 containing furanocoumarin imperatorin showed antiproliferative activity against leukaemia cell line with IC 50 of 12.5 μg/ml.

  18. The Acetone Extract of Sclerocarya birrea (Anacardiaceae Possesses Antiproliferative and Apoptotic Potential against Human Breast Cancer Cell Lines (MCF-7

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    Nicoline Fri Tanih

    2013-01-01

    Full Text Available Interesting antimicrobial data from the stem bark of Sclerocarya birrea, which support its use in traditional medicine for the treatment of many diseases, have been delineated. The current study was aimed to further study some pharmacological and toxicological properties of the plant to scientifically justify its use. Anticancer activity of water and acetone extracts of S. birrea was evaluated on three different cell lines, HT-29, HeLa, and MCF-7 using the cell titre blue viability assay in 96-well plates. Apoptosis was evaluated using the acridine orange and propidium iodide staining method, while morphological structure of treated cells was examined using SEM. The acetone extract exhibited remarkable antiproliferative activities on MCF-7 cell lines at dose- and time-dependent manners (24 h and 48 h of incubation. The extract also exerted apoptotic programmed cell death in MCF-7 cells with significant effect on the DNA. Morphological examination also displayed apoptotic characteristics in the treated cells, including clumping, condensation, and culminating to budding of the cells to produce membrane-bound fragmentation, as well as formation of apoptotic bodies. The acetone extract of S. birrea possesses antiproliferative and apoptotic potential against MCF-7-treated cells and could be further exploited as a potential lead in anticancer therapy.

  19. Cytotoxic and Antiproliferative Effect of Tepary Bean Lectins on C33-A, MCF-7, SKNSH, and SW480 Cell Lines

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    Carmen Valadez-Vega

    2014-07-01

    Full Text Available For many years, several studies have been employing lectin from vegetables in order to prove its toxic effect on various cell lines. In this work, we analyzed the cytotoxic, antiproliferative, and post-incubatory effect of pure tepary bean lectins on four lines of malignant cells: C33-A; MCF-7; SKNSH, and SW480. The tests were carried out employing MTT and 3[H]-thymidine assays. The results showed that after 24 h of lectin exposure, the cells lines showed a dose-dependent cytotoxic effect, the effect being higher on MCF-7, while C33-A showed the highest resistance. Cell proliferation studies showed that the toxic effect induced by lectins is higher even when lectins are removed, and in fact, the inhibition of proliferation continues after 48 h. Due to the use of two techniques to analyze the cytotoxic and antiproliferative effect, differences were observed in the results, which can be explained by the fact that one technique is based on metabolic reactions, while the other is based on the 3[H]-thymidine incorporated in DNA by cells under division. These results allow concluding that lectins exert a cytotoxic effect after 24 h of exposure, exhibiting a dose-dependent effect. In some cases, the cytotoxic effect is higher even when the lectins are eliminated, however, in other cases, the cells showed a proliferative effect.

  20. Antiproliferative activity of buttermilk lipid fractions isolated using food grade and non-food grade solvents on human cancer cell lines.

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    Castro-Gómez, Pilar; Rodríguez-Alcalá, Luis M; Monteiro, Karin M; Ruiz, Ana L T G; Carvalho, João E; Fontecha, Javier

    2016-12-01

    Buttermilk is a dairy by-product with a high content of milk fat globule membranes (MFGMs), whose protein constituents are reported to be antiproliferative. Lipids represent about half of the composition of MFGM. The aim of this study was to isolate buttermilk lipid fractions and evaluate their potential antiproliferative effect. Selective extraction with food grade or non-food grade solvents was performed. Antiproliferative effectiveness of lipid extracts and their neutral and polar fractions was evaluated on nine human cancer cell lines. Fractions obtained using food grade ethanol gave a higher yield than those obtained using non-food grade solvents, and they effectively inhibited cell viability of the cancer cell lines investigated. These fractions, rich in phospho- and sphingolipids, were strongly antiproliferative against human ovary and colon cancer cells. This observation allowed us to hypothesize further analyses aimed at promoting the use of buttermilk polar lipid fractions as functional food additives. PMID:27374586

  1. Synergistic antiproliferative and anticholesterogenic effects of linalool, 1,8-cineole, and simvastatin on human cell lines.

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    Rodenak Kladniew, Boris; Polo, Mónica; Montero Villegas, Sandra; Galle, Marianela; Crespo, Rosana; García de Bravo, Margarita

    2014-05-01

    Monoterpenes are naturally occurring plant hydrocarbons with multiple effects on the mevalonate pathway (MP), while statins competitively inhibit hydroxymethylglutarylcoenzyme-A reductase (HMGCR), the rate-limiting enzyme in the MP. Monoterpenes and statins proved capable of inhibiting both proliferation and cholesterogenesis. In the present study we assess the in vitro antiproliferative and anticholesterogenic effects of two monoterpenes: linalool and 1,8-cineole-either alone, in combination with each other, or combined individually with simvastatin-on liver-derived (HepG2) and extrahepatic (A549) cell lines. The three compounds alone inhibited cell proliferation in a dose-dependent fashion, while their pairwise combination produced synergistic antiproliferative effects in both cell lines. Incorporation experiments with [(14)C]acetate revealed that linalool and 1,8-cineole inhibited the MP, probably at different points, resulting in a reduction in cholesterogenesis and an accumulation of other MP intermediates and products. Linalool or 1,8-cineole, either together or individually with simvastatin, synergistically inhibited cholesterol synthesis. At low concentrations both monoterpenes inhibited steps specifically involved in cholesterol synthesis, whereas at higher concentrations HMGCR levels became down-regulated. Added exogenous mevalonate failed to reverse the inhibition of proliferation exerted by linalool and 1,8-cineole, suggesting that HMGCR inhibition alone is not responsible for the antiproliferative activity of those agents. This work demonstrates that monoterpenes in combination with each other, or individually in combination with simvastatin synergistically inhibits proliferation and cholesterogenesis in the human cell lines investigated, thus contributing to a clearer understanding of the action of essential-oil components, and their combination with the statins, in the targeting of specific points within a complex metabolic pathway.

  2. Antiproliferative effects of Plumbago rosea and its purified constituent plumbagin on SK-MEL 28 melanoma cell lines

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    Alexander Ronaldo Anuf

    2014-01-01

    Full Text Available Background: Plumbago rosea is used in traditional systems of medicine for the preparation of formulations used for treating inflammations, cough, bronchitis, and gastrointestinal disorders, and also in conjunction with cancer chemotherapy. In the present study, the cytotoxic and anti-proliferative effects of plumbagin, and the ethanolic root extract of P. rosea (ETPR was evaluated on SK-MEL 28 melanoma cell lines and human lymphocytes. Materials and Methods: MTT and apoptotic assays were used for the evaluation of cytotoxic and anti-proliferative effects, respectively. In addition, the effect of Plumbagin and ETPR in down regulation of BCL-2 expression is investigated using RT-PCR analysis. Results: Both plumbagin and ETPR dose-dependently decreased the cell viability more potently in melanoma cell lines. P. rosea extract demonstrated significant synergy in inhibiting BCL-2 expression than plumbagin. Moreover plumbagin showed more toxicity in human lymphocytes. Conclusion: Plumbagin has anti-cancer potential, but the side effects limits its use; yet plumbagin, in combination with other ingredients in Plumbago rosea extract, displays significant synergy leading to a stronger anticancer effect with significantly less toxicity.

  3. Comparison of the antiproliferative activity of crude ethanol extracts of nine salvia species grown in Jordan against breast cancer cell line models

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    Rana Abu-Dahab

    2012-01-01

    Full Text Available Background: The antiproliferative activity of Salvia species grown in Jordan has not been fully evaluated yet. The aim of this work was to study the antiproliferative activity of crude ethanol extracts from nine Salvia species grown in Jordan against a panel of breast cancer cell lines. Material and Methods: Cytotoxic activity was evaluated in human tumor models of breast cancer; MCF-7, T47D, ZR-75-1, and BT 474 by the sulforhodamine B assay. In addition, the extracts were evaluated using a non-transformed cell line (Vero and normal fibroblast cells in order to demonstrate their selectivity and safety. Results: From the nice ethanol extracts under investigation, those of S. dominica and S. fruticosa showed an inhibitory concentration of 50% of cells (IC 50 in concentrations less than 30μg/mL against the four cell lines under investigation. S. syriaca and S. hormium showed an IC 50 below 30μg/ml for two out of the four cell lines. S. fruticosa, S. hormium and S. syriaca showed selectivity in their antiproliferative activity against estrogen receptor positive cell lines with minimal toxicity against normal human periodontal fibroblasts. Phytochemical screening using thin layer chromatography indicated the presence of terpenoids, flavonoids and coumarins in all examined extracts. Conclusion: Three of the plant extracts under investigation exhibited antiproliferative activity against breast cancer cells and were shown to be safe and selective. These could be considered as a potential source for novel anticancer therapy.

  4. Isolation and antiproliferative activity of Lotus corniculatus lectin towards human tumour cell lines.

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    Rafiq, Shaista; Majeed, Rabiya; Qazi, Asif Khurshid; Ganai, Bashir Ahmad; Wani, Ishfak; Rakhshanda, Syed; Qurishi, Yasrib; Sharma, P R; Hamid, Abid; Masood, Akbar; Hamid, Rabia

    2013-12-15

    The objective of the study was to investigate the anti cancer activity of a lectin isolated from Lotus corniculatus seeds. A tetrameric 70kDa galactose specific lectin was purified using two step simple purification protocol which involved affinity chromatography on AF-BlueHC650M and gel filtration on Sephadex G-100. The lectin was adsorbed on AF-BlueHC650M and desorbed using 1M NaCl in the starting buffer. Gel filtration on Sephadex G-100 yielded a major peak absorbance that gave two bands of 15kDa and 20kDa in SDS PAGE. Hemagglutination activity was completely preserved, when the temperature was in the range of 20-60°C. However, drastic reduction in activity occurred at temperatures above 60°C. Full hemagglutination activity was retained at ambient pH 4-12. Thereafter no activity was observed above pH 13. Hemaglutination of the lectin was inhibited by d-galactose. The lectin showed a strong antiproliferative activity towards human leukemic (THP-1) cancer cells followed by lung cancer (HOP62) cells and HCT116 with an IC50 of 39μg/ml and 50μg/ml and 60μg/ml respectively. Flow cytometry analysis showed an increase in the percentage of cells in sub G0G1 phase confirming that Lotus corniculatus lectin induced apoptosis. Morphological observations showed that Lotus corniculatus lectin (LCL) treated THP-1 cells displayed apparent apoptosis characteristics such as nuclear fragmentation, appearance of membrane enclosed apoptotic bodies and DNA fragmentation. Lotus corniculatus lectin (LCL) effectively inhibits the cell migration in a dose dependent manner as indicated by the wound healing assay.

  5. The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line.

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    Riva, L; Coradini, D; Di Fronzo, G; De Feo, V; De Tommasi, N; De Simone, F; Pizza, C

    2001-01-01

    Uncaria tomentosa, also known as "Uña de gato", is a Rubiaceae species widely used in South-American folk medicine for the treatment of cancer, arthritis, gastritis and epidemic diseases. Extracts of the plant have been shown to possess cytostatic and anti-inflammatory activity as well as mutagenic and antimutagenic properties. However, to date no studies have been carried out to verify the direct antitumor activity of the extracts. The present study investigates the effects of some extracts and their chromatographic fractions from the bark of U. tomentosa on the growth of a human breast cancer cell line (MCF7). Our data indicated that, in addition to the antimutagenic activity, U. tomentosa extracts and fractions exert a direct antiproliferative activity on MCF7. The bioassay-directed fractionation from barks and leaves resulted in the isolation of two active fractions, which displayed an IC50 of 10 mg/ml and 20 mg/ml, respectively and an antiproliferative effect, with about 90% of inhibition at a concentration of 100 mg/ml.

  6. Evaluation of Antiproliferative Activity of Red Sorghum Bran Anthocyanin on a Human Breast Cancer Cell Line (MCF-7)

    International Nuclear Information System (INIS)

    Breast cancer is a leading cause of death in women worldwide both in the developed and developing countries. Thus effective treatment of breast cancer with potential antitumour drugs is important. In this paper, human breast cancer cell line MCF-7 has been employed to evaluate the antiproliferative activity of red sorghum bran anthocyanin. The present investigation showed that red sorghum bran anthocyanin induced growth inhibition of MCF-7 cells at significant level. The growth inhibition is dose dependent and irreversible in nature. When MCF-7 cells were treated with red sorghum bran anthocyanins due to activity of anthocyanin morphological changes were observed. The morphological changes were identified through the formation of apoptopic bodies. The fragmentation by these anthocyanins on DNA to oligonuleosomal-sized fragments, is a characteristic of apoptosis, and it was observed as concentration-dependent. Thus, this paper clearly demonstrates that human breast cancer cell MCF-7 is highly responsive by red sorghum bran anthocyanins result from the induction of apoptosis in MCF-7 cells.

  7. Antiproliferative activity of flower hexane extract obtained from Mentha spicata associated with Mentha rotundifolia against the MCF7, KB, and NIH/3T3 cell lines.

    Science.gov (United States)

    Nedel, Fernanda; Begnini, Karine; Carvalho, Pedro Henrique de Azambuja; Lund, Rafael Guerra; Beira, Fátima T A; Del Pino, Francisco Augusto B

    2012-11-01

    This study assessed the antiproliferative effect in vitro of the flower hexane extract obtained from Mentha spicata associated with Mentha rotundifolia against the human breast adenocarcinoma (MCF-7), human mouth epidermal carcinoma (KB), and mouse embryonic fibroblast (NIH 3T3) cell lines, using sulforhodamine B (SRB) assay. A cell density of 2×10(4)/well was seeded in 96-well plates, and samples at different concentrations ranging from 10 to 500 mg/mL were tested. The optical density was determined in an ELISA multiplate reader (Thermo Plate TP-Reader). Results demonstrated that the hexane extract presented antiproliferative activity against both the tumor cell lines KB and MCF-7, presenting a GI(50) (MCF-7=13.09 mg/mL), TGI (KB=37.76 mg/mL), and IL(50) (KB=291.07 mg/mL). Also, the hexane extract presented antiproliferative activity toward NIH 3T3 cells GI(50) (183.65 mg/mL), TGI (280.54 mg/mL), and IL(50) (384.59 mg/mL). The results indicate that the flower hexane extract obtained from M. spicata associated with M. rotundifolia presents an antineoplastic activity against KB and MCF-7, although an antiproliferative effect at a high concentration of the extract was observed toward NIH 3T3. PMID:23066647

  8. Antiproliferative activity of flower hexane extract obtained from Mentha spicata associated with Mentha rotundifolia against the MCF7, KB, and NIH/3T3 cell lines.

    Science.gov (United States)

    Nedel, Fernanda; Begnini, Karine; Carvalho, Pedro Henrique de Azambuja; Lund, Rafael Guerra; Beira, Fátima T A; Del Pino, Francisco Augusto B

    2012-11-01

    This study assessed the antiproliferative effect in vitro of the flower hexane extract obtained from Mentha spicata associated with Mentha rotundifolia against the human breast adenocarcinoma (MCF-7), human mouth epidermal carcinoma (KB), and mouse embryonic fibroblast (NIH 3T3) cell lines, using sulforhodamine B (SRB) assay. A cell density of 2×10(4)/well was seeded in 96-well plates, and samples at different concentrations ranging from 10 to 500 mg/mL were tested. The optical density was determined in an ELISA multiplate reader (Thermo Plate TP-Reader). Results demonstrated that the hexane extract presented antiproliferative activity against both the tumor cell lines KB and MCF-7, presenting a GI(50) (MCF-7=13.09 mg/mL), TGI (KB=37.76 mg/mL), and IL(50) (KB=291.07 mg/mL). Also, the hexane extract presented antiproliferative activity toward NIH 3T3 cells GI(50) (183.65 mg/mL), TGI (280.54 mg/mL), and IL(50) (384.59 mg/mL). The results indicate that the flower hexane extract obtained from M. spicata associated with M. rotundifolia presents an antineoplastic activity against KB and MCF-7, although an antiproliferative effect at a high concentration of the extract was observed toward NIH 3T3.

  9. [Validation of the Antiproliferative Effects of Euphorbia tirucalli Extracts in Breast Cancer Cell Lines].

    Science.gov (United States)

    Choene, M; Motadi, L

    2016-01-01

    Medicinal plant extracts have recently attracted attention of modern medical science research due to their non-lethal activity. Currently, up to 50% of the world drugs including chemotherapeutic drugs such as taxol and camptothecin are derived from natural products. Euphorbia tirucalli has a long history of usage as traditional medicine in Africa and has been widely used in the treatment of different cancers. In this study, we explore the medical properties of E. tirucalli extracts in breast cancer development. To achieve this, stems of E. tirucalli were dried, crushed and extracted with butanol, hexane or methanol (based on 1 g of dry substance in 10 mL of a solvent). The dried extracts were re-dissolved in DMSO and investigated. Composition of each extract was analyzed using liquid chromatography-mass spectroscopy (LC-MS). Extracts were found to contain different types of secondary metabolites mainly terpenes and flavonoids. Breast cancer cell lines (MCF-7 and MDA-MB 231) were treated with various concentrations of the extracts for up to 48 h. Cell viability, cell cycle, apoptosis and gene expression were analysed. In cells, extracts were found to inhibit cell proliferation in a concentration and cell type dependent manner. Analysis of the cause of antiproliferation revealed that most cells were arrested at the G0/G1 phase by p21 overexpression. In general, most pro-apoptotic genes like Bax and caspase-8 were significantly up-regulated in cells treated with plant extracts. These results suggest that the extracts might induce cell cycle arrest at G0/G1 with p21 attributing to this molecular mechanism. PMID:27028817

  10. Antiproliferative effect of Phytosome complex of Met hanolic extact of Terminalia Arjuna bark on Human Breast Cancer Cell Lines (MCF-7

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    Sharma Shalini 1

    2015-03-01

    Full Text Available Methanolic extract of Terminalia arjuna Roxb of family combretaceae is rich in flavonoids content which are responsible for its antiproliferative activity but these bioactive constituents have poor oral and topical absorption either due to the large molecular weight or poor miscibility with lipids. These poorly soluble herbal extracts can be converted into lipid compatible molecular complexes called phytosomes by binding individual constituents of the herbal extractto phosphatidylcholine. Phytosomes are known to show improved oral and topical absorption followed by enhanced activity as compared to pure herbal extracts. This study was aimed at preparing methanolic extract of Terminalia arjuna bark and Terminalia arjuna bark Extract Phytosome and investigating their antiproliferative activity on human MCF-7 cell line by MTT assay. Comparison of the antiproliferative activity was done with with quercetin and its phytosomes. IC50of methanolic extract of Terminalia arjuna bark and Terminalia arjuna bark Extract Phytosome against cancer cell lines MCF-7 was found to be 25μg/ml and 15μg/ml respectively whereas that of quercetin and its phytosomes was found to be 2μg/ml and 0.7μg/ml respectively. The results suggests that Terminalia arjuna bark Extract Phytosome & quercetin phytosomes are active pharmacologically and exerts more antiproliferative effect on MCF-7 cells as compared to pure methanolic extract of plant and pure quercetin respectively.

  11. Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines

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    Zou Zhengyun

    2012-04-01

    Full Text Available Summary Background Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. Methods MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. Results Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Conclusions Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

  12. Antiproliferative effect of silver nanoparticles synthesized using amla on Hep2 cell line

    Institute of Scientific and Technical Information of China (English)

    Fathima Stanley Rosarin; Vadivel Arulmozhi; Samuthira Nagarajan; Sankaran Mirunalini

    2013-01-01

    Objective: To synthesize silver nanoparticles by amla extract, screen the cytotoxic, oxidative stress and apoptotic effect of silver nanoparticles (AgNPs) on Hep2 cell line (laryngeal carcinoma cells) in vitro, and to compare the effect of Phyllanthus emblica (P. emblica) (amla) with AgNPs synthesized by amla and 5-FU. Methods: AgNPs was synthesized by P. emblica (aqueous extract) and nanoparticles were characterized UV-Vis spec, the presence of biomoloecules of amla capped in AgNPs was found by FT-IR analysis, shape and size were examined by SEM and DLS. Cytotoxicity of experimental drugs was tested to find IC50 value. ROS generation in cells have been measured by DCFH-DA staining, AO-EtBr, Rhodamine-123 staining and DNA fragmentation were performed to assess apoptotic cell death, mitochondrial membrane potential and apoptotic DNA damage, respectively. Oxidative stress was analyzed by measuring lipid peroxides and antioxidants level to understand the cancer cell death by pro-oxidant mechanism.Results:PE-AgNPs was synthesized and confirmed through kinetic behavior of NPs. The shape of PE-AgNPs was spherical and cubic since it was agglomerated, and the nanoparticle surface was complicated. Average particle size distribution of PE-AgNPs was found to be 188 nm. Potent biomolecules of P. emblica such as polyphenols were capped with AgNPs and reduced its toxicity. In cytotoxicity assay the concentration in which the maximum number of cell death was 60 μg/mL and 50 μg/mL for P. emblica (alone) and AgNPs, respectively and IC50 values were fixed as 30 μg/mL and 20 μg/mL. ROS generation, apoptotic morphological changes, mitochondrial depolarization, DNA damage and oxidative stress was observed as more in AgNPs treated cells than in P. emblica (30 μg/mL) (alone) treated cells and 5-FU treated cells gave similar result.Conclusions:The results suggest that the AgNPs are capped with biomolecules of amla enhanced cytotoxicity in laryngeal cancer cells through oxidative

  13. Benzoxazinoids from Scoparia dulcis (sweet broomweed) with antiproliferative activity against the DU-145 human prostate cancer cell line.

    Science.gov (United States)

    Wu, Wan-Hsun; Chen, Tzu-Yu; Lu, Rui-Wen; Chen, Shui-Tein; Chang, Chia-Chuan

    2012-11-01

    Sweet broomweed (Scoparia dulcis) is an edible perennial medicinal herb widely distributed in tropical and subtropical regions of Asia, Africa, and the Americas. Four compounds, (2R)-7-methoxy-2H-1,4-benzoxazin-3(4H)-one 2-O-β-galactopyranoside [(2R)-HMBOA-2-O-Gal], 3,6-dimethoxy-benzoxazolin-2(3H)-one (3,6-M2BOA), 3-hydroxy-6-methoxy-2-benzoxazolinone (3-OH-MBOA), and scutellarein 7-O-β-glucuronamide, along with eight known compounds, including two 7-methoxy-1,4-benzoxazin-3(2H)-one 3-O-hexopyranosides [(2R)-HMBOA-2-O-Glc and (2R)-HDMBOA-2-O-Glc], 6-methoxy-benzoxazolin-2(3H)-one (MBOA), acteoside, sodium scutellarin, p-coumaric acid, and two monosaccharides (fructose and glucose), were isolated from the aqueous extract of S. dulcis. Antiproliferative activities of the six benzoxazinoid compounds against the DU-145 human prostate cancer cell line were assayed, and one of these displayed an IC₅₀ of 65.8 μg/mL. PMID:22944352

  14. Antiproliferative effect of rapamycin on human T-cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition

    Institute of Scientific and Technical Information of China (English)

    Yan-min ZHAO; Qian ZHOU; Yun XU; Xiao-yu LAI; He HUANG

    2008-01-01

    Aim:To examine the ability of rapamycin to suppress growth and regulate telomerase activity in the human T-cell leukemia cell line Jurkat. Methods:Cell proliferation was assessed after exposure to rapamycin by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were determined by flow cytometry. The proteins important for cell cycle progres-sion and Akt/mammalian target of rapamycin signaling cascade were assessed by Western blotting. Telomerase activity was quantified by telomeric repeat amplication protocol assay. The human telomerase reverse transcriptase (hTERT) mRNA levels were determined by semi-quantitative RT-PCR. Results:Rapamycin inhibited the proliferation of Jurkat, induced G1 phase arrest, unregulated the pro-tein level of p21 as well as p27, and downregulated cyclinD3, phospho-p70s6k, and phospho-s6, but had no effect on apoptosis. Treatment with rapamycin reduced telomerase activity, and reduced hTERT mRNA and protein expression. Conclusion:Rapamycin displayed a potent antileukemic effect in the human T-cell leukemia cell line by inhibition of cell proliferation through G1 cell cycle arrest and also through the suppression of telomerase activity, suggesting that rapamycin may have potential clinical implications in the treatment of some leukemias.

  15. Synergistic Antiproliferative Effects of a New Cucurbitacin B Derivative and Chemotherapy Drugs on Lung Cancer Cell Line A549.

    Science.gov (United States)

    Marostica, Lucas Lourenço; Silva, Izabella Thaís; Kratz, Jadel Müller; Persich, Lara; Geller, Fabiana Cristina; Lang, Karen Luise; Caro, Miguel Soriano Balparda; Durán, Fernando Javier; Schenkel, Eloir Paulo; Simões, Cláudia Maria Oliveira

    2015-10-19

    Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer.

  16. Antiproliferative Effects of Alkaloids Isolated from the Tuber of Stephania venosa via the Induction of Cell Cycle Arrest in Mammalian Cancer Cell Lines

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    Sirinapa Nantapap

    2010-01-01

    Full Text Available Problem statement: S. venosa (Menispermaceae is used in traditional medicine. The constituents of S. venosa belonging to showed remarkable cytotoxic activity. According to previous research, S. venosa contains several alkaloids, such as protoberberine stephanine cyclanoline and N-methylstepholidine, kamaline, (+-N-carboxamidostepharine, (--O-methylstepharinosine, (--stepharinosine, aporphine (--O-acethylsukhodiamine and oxostephanosine. The chemical and biological investigations of this plant are interesting to bioassay-guided fractionation, particularly Antiproliferative effects via the induction of cell cycle arrest in mammalian cancer cell lines. Approach: The research was carried out to extract, isolate, purify and elucidate structure of the active compound from the tuber S. venosa. Most of the solvent extracts and isolated compound were evaluated with kinds of mammalian cancer cell lines for investigation on antiproliferative effects. Results: Four alkaloids, tetrahydropalmatine (1, crebanine (2 O-methylbulbocapnine (3 and N-methyltetrahydropalmatine (4 were isolated from the tuber of S. venosa. Charaterization of the compounds were carried out by extensive NMR studies using COSY, HMQC, HMBC and DEPT in addition to other spectroscopic methods. These compounds (1, 2 and 3 were showed evidence of the anticancer activities for cell proliferation inhibition in K562, K562/Adr, GLC4 and GLC4/Adr cell lines due to G0/G1 obstruction by compound 2 and 3 and negligible S phase arrest by compound 1. Conclusion: The result showed slightly increase in S phase by the effect of compound 1, beside the G0/G1 phase was blocked by compound 2 and 3.

  17. Essential oil content of the rhizome of Curcuma purpurascens Bl. (Temu Tis) and its antiproliferative effect on selected human carcinoma cell lines.

    Science.gov (United States)

    Hong, Sok-Lai; Lee, Guan-Serm; Syed Abdul Rahman, Syarifah Nur; Ahmed Hamdi, Omer Abdalla; Awang, Khalijah; Aznam Nugroho, Nurfina; Abd Malek, Sri Nurestri

    2014-01-01

    Curcuma purpurascens Bl., belonging to the Zingiberaceae family, is known as temu tis in Yogyakarta, Indonesia. In this study, the hydrodistilled dried ground rhizome oil was investigated for its chemical content and antiproliferative activity against selected human carcinoma cell lines (MCF7, Ca Ski, A549, HT29, and HCT116) and a normal human lung fibroblast cell line (MRC5). Results from GC-MS and GC-FID analysis of the rhizome oil of temu tis showed turmerone as the major component, followed by germacrone, ar-turmerone, germacrene-B, and curlone. The rhizome oil of temu tis exhibited strong cytotoxicity against HT29 cells (IC50 value of 4.9 ± 0.4 μg/mL), weak cytotoxicity against A549, Ca Ski, and HCT116 cells (with IC50 values of 46.3 ± 0.7, 32.5 ± 1.1, and 35.0 ± 0.3 μg/mL, resp.), and no inhibitory effect against MCF7 cells. It exhibited mild cytotoxicity against a noncancerous human lung fibroblast cell line (MRC5), with an IC50 value of 25.2 ± 2.7 μg/mL. This is the first report on the chemical composition of this rhizome's oil and its selective antiproliferative effect on HT29. The obtained data provided a basis for further investigation of the mode of cell death.

  18. Anti-proliferative activity of hop-derived prenylflavonoids against human cancer cell lines.

    Science.gov (United States)

    Busch, Christian; Noor, Seema; Leischner, Christian; Burkard, Markus; Lauer, Ulrich M; Venturelli, Sascha

    2015-06-01

    Flavonoids form a substantial group of secondary plant metabolites that display several health-promoting effects. Therefore, prenylflavonoids, a subclass of flavonoids, have attracted increasing attention. Here, we investigated the possible anti-cancer potential of 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN), two prenylflavonoids present in hops and beer and demonstrate an unexpectedly pronounced, dose-dependent reduction of cellular proliferation of human PC-3 prostate cancer and UO.31 renal carcinoma cells upon treatment. Based on these findings 6-PN and 8-PN are currently further clinically evaluated in detail. PMID:25925225

  19. Evaluation of the Volatile Oil Composition and Antiproliferative Activity of Laurus nobilis L. (Lauraceae on Breast Cancer Cell Line Models

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    Rana Abu-Dahab

    2014-03-01

    Full Text Available Volatile oil composition and antiproliferative activity of Laurus nobilis L. (Lauraceae fruits and leaves grown in Jordan were investigated. GC-MS analysis of the essential oil of the fruits resulted in the identification of 45 components representing 99.7 % of the total oil content, while the leaf essential oil yielded 37 compounds representing 93.7% of the total oil content. Oxygenated monoterpene 1,8-cineole was the main component in the fruit and leaf oils. Using sulphorhodamine B assay; the crude ethanol fraction, among other solvent extracts, showed strong antiproliferative activity for both leaves and fruits, nevertheless, the fruits were more potent against both breast cancer cell models (MCF7 and T47D. At IC 50 values ; the mechanism of apoptosis was nevertheless different: where L. nobilis fruit proapoptotic efficacy was not regulated by either p53 or p21, L. nobilis leaf extract components enhanced the p53 levels substantially. In both extracts, apoptosis was not caspase-8 or Fas Ligand and sFas (Fas/APO-1 dependent. Our studies highlight L. nobilis as a potential natural agent for breast cancer therapy. Compared with non induced basal cells, both L. nobilis fruits and leaves induced a significant enrichment in the cytoplasmic mono- and oligonucleosomes after assumed induction of programmed MCF7 cell death.

  20. In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis

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    Teerasripreecha Dungporn

    2012-03-01

    Full Text Available Abstract Background Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. Methods Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity in vitro against five human cell lines derived from duet carcinoma (BT474, undifferentiated lung (Chaco, liver hepatoblastoma (Hep-G2, gastric carcinoma (KATO-III and colon adenocarcinoma (SW620 cancers. The human foreskin fibroblast cell line (Hs27 was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy. Results The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC50 values across the five cancer cell lines ranging from 41.3 to 52.4 μg/ml and from 43.8 to 53.5 μg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC50 values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 μg/ml for the cardanol and . Conclusion This is the first report that Thai A. mellifera propolis contains at least two potentially new compounds (a cardanol and a cardol with potential anti

  1. Dual Anti-Metastatic and Anti-Proliferative Activity Assessment of Two Probiotics on HeLa and HT-29 Cell Lines

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    Nouri Zahra

    2016-07-01

    Full Text Available Objective Lactobacilli are a group of probiotics with beneficial effects on prevention of cancer. However, there is scant data in relation with the impacts of probiotics in late-stage cancer progration, especially metastasis. The present original work was aimed to evaluate the anti-metastatic and anti-proliferative activity of lactobacillus rhamnosus supernatant (LRS and lactobacillus crispatus supernatant (LCS on the human cervical and colon adenocarcinoma cell lines (HeLa and HT-29, respectively. Materials and Methods In this experimental study, the anti-proliferative activities of LRS and LCS were determined through MTT assay. MRC-5 was used as a normal cell line. Expression analysis of CASP3, MMP2, MMP9, TIMP1 and TIMP2 genes was performed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR, following the cell synchronization. Results Supernatants of these two lactobacilli had cytotoxic effect on HeLa, however LRS treatment was only effective on HT-29 cell line. In addition, LRS had no side-effect on normal cells. It was shown that CASP3 gene expression has been reduced after treatment with supernatants of two studied lactobacilli. According to our study, LRS and LCS are efficacious in the prevention of metastasis potency in HeLa cells with decreased expression of MMP2, MMP9 and increased expression of their inhibitors. In the case of HT-29 cells, only LRS showed this effect. Conclusion Herein, we have demonstrated two probiotics which have anti-metastatic effects on malignant cells and they can be administrated to postpone late-stage of cancer disease. LRS and LCS are effective on HeLa cell lines while only the effect of LRS is significant on HT-29, through cytotoxic and anti-metastatic mechanisms. Further assessments are required to evaluate our results on the other cancer cell lines, in advance to use these probiotics in other extensive trial studies.

  2. Gracilaria edulis exhibit antiproliferative activity against human lung adenocarcinoma cell line A549 without causing adverse toxic effect in vitro and in vivo.

    Science.gov (United States)

    Sakthivel, Ravi; Muniasamy, Samuthirapandi; Archunan, Govindaraju; Devi, Kasi Pandima

    2016-02-01

    In the present study, the antiproliferative potential of various solvent extracts of Gracilaria edulis (GE) was tested against various cancer cell lines. In the A549 lung cancer cell line model, GE ethyl acetate extract (GEEA) (100 μg mL(-1)) treated group showed the maximum and significant (P < 0.05) growth inhibition at 48 h. The IC50 value was found to be 24.5 ± 19.1 μg mL(-1) at 48 h. Moreover, a low level of LDH release was observed at 48 h at various concentrations of (40, 60, 80 and 100 μg mL(-1)) GEEA extract-treated group compared to a control group. Changes in the cell morphology and echinoid spikes formation were observed at 48 h. Safety evaluation of GEEA in a non-cancerous liver cell line, PBMC and in Wistar rats positively revealed that the extract did not show any adverse toxic effects. The GEEA extract was partially purified by column chromatography and the active fraction was characterized through LC-MS analysis. Furthermore, HPLC and FT-IR analysis of the active fractions confirmed the presence of phytol, a diterpene compound with potent antiproliferative activity, which positively suggests that the red alga G. edulis contains a potent anticancer active principle.

  3. Antiproliferative and pro-apoptotic effects of quercetin on human pancreatic carcinoma cell lines EPP85-181P and EPP85-181RDB.

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    Malgorzata Dumanska

    2010-08-01

    Full Text Available Polyphenols are present in several edible plants and for many years induce high interest mainly due to their antioxidative and anti-inflammatory influence. At present, numerous studies are conducted on antineoplastic effects of the compounds. One of most effective biopolyphenols involves the flavonol quercetin. Our studies aimed at evaluation of antiproliferative and pro-apoptotic effects of quercetin alone and in combinations with daunorubicin on cells of human pancreatic carcinoma lines. The experiments were conducted on two cell lines, sensitive to daunorubicin EPP85-181P line, and its resistant variant EPP85-181RDB. Effect of studied substances on cell proliferation was detected using sulphorhodamine B (SRB protein staining method. Apoptotic damage was estimated using comet and TUNEL techniques. Our data demonstrated that quercetin exerted cytotoxic action on cells of the both neoplastic cell lines in concentration-dependent manner. In the case of EPP85-181RDB cell line, quercetin seemed to sensitize resistant cells to daunorubicin. In parallel, the effect of both substances on the sensitive cell line was synergistic. Results of the studies confirmed that quercetin may probably break resistance of neoplastic cells to chemotherapy. On the other side, studied flavonol augmented action of cytostatic drug in case of sensitive tumour cells what suggest, that it might allow to decrease dosage of cytostatic drugs and reduce negative side effects of the treatment.

  4. In vitro antiproliferative effect of a water-soluble Laminaria japonica polysaccharide on human melanoma cell line A375.

    Science.gov (United States)

    Peng, Zhenfei; Liu, Min; Fang, Zhexiang; Chen, Li; Wu, Jiulin; Zhang, Qiqing

    2013-08-01

    A water-soluble polysaccharide WPS-2-1, purified from Laminaria japonica, has been found to have antitumor activity. In this study, WPS-2-1 exhibited high anti-proliferative activity on A375 cells in a dosedependent manner. Further investigation indicated that WPS-2-1 induced A375 cells apoptosis. Moreover, WPS-2-1-induced apoptosis was associated with the alteration in expressions of Bcl-2 family proteins. Mitochonadrial apoptotic pathway was involved in WPS-2-1-induced apoptosis, which included the loss of mitochondrial membrane and activation of caspase-3/9. The results in this study suggested that WPS-2-1 could effectively inhibit proliferation of A375 cells in vitro and induce apoptosis via mitochondrial apoptotic pathway. It might serve as a potential antitumor agent.

  5. Screening of antiproliferative effect of aqueous extracts of plant foods consumed in México on the breast cancer cell line MCF-7.

    Science.gov (United States)

    García-Solís, Pablo; Yahia, Elhadi M; Morales-Tlalpan, Verónica; Díaz-Muñoz, Mauricio

    2009-01-01

    We evaluated the antiproliferative effect of aqueous extracts of 14 plant foods consumed in Mexico on the breast cancer cell line MCF-7. The plant foods used were avocado, black sapote, guava, mango, prickly pear cactus stems (called nopal in Mexico, cooked and raw), papaya, pineapple, four different cultivars of prickly pear fruit, grapes and tomato. β-Carotene, total phenolics and gallic acid contents and the antioxidant capacity, measured by the ferric reducing/antioxidant power and the 2,2-diphenyl-1,1-picrylhydrazyl radical scavenging assays, were analyzed in each aqueous extract. Only the papaya extract had a significant antiproliferative effect measured with the methylthiazolydiphenyl-tetrazolium bromide assay. We did not notice a relationship between the total phenolic content and the antioxidant capacity with antiproliferative effect. It is suggested that each extract of plant food has a unique combination of the quantity and quality of phytochemicals that could determine its biological activity. Besides, papaya represents a very interesting fruit to explore its antineoplastic activities. PMID:19468947

  6. Apoptosis-mediated antiproliferative activity of friedolanostane triterpenoid isolated from the leaves of Garcinia celebica against MCF-7 human breast cancer cell lines

    Science.gov (United States)

    SUBARNAS, ANAS; DIANTINI, AJENG; ABDULAH, RIZKY; ZUHROTUN, ADE; NUGRAHA, PATRIA A.; HADISAPUTRI, YUNI E.; PUSPITASARI, IRMA M.; YAMAZAKI, CHIHO; KUWANO, HIROYUKI; KOYAMA, HIROSHI

    2016-01-01

    The leaves of Garcinia celebica strongly inhibit the proliferation of MCF-7 human breast adenocarcinoma cell lines. The present study focused on investigating the active anticancer and antiproliferative compound from the G. celebica leaves and assessing its mechanism of action. Ethanol extracts of G. celebica were fractionated based on their polarity using n-hexane, ethyl acetate and water. The antiproliferative properties were tested in vitro against MCF-7 human breast cancer cell lines using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. The active compound was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested for its antiproliferative properties and the mechanism by which it induces apoptosis in MCF-7 cells by western blot analysis of the activated apoptotic proteins. This resulted in the isolation of a friedolanostane triterpenoid, which was determined to be methyl-3α, 23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat. This compound inhibited MCF-7 cell proliferation in a time- and dose-dependent manner with IC50 values of 82 and 70 µM for the 24 and 48 h treatments, respectively. Furthermore, the western blot analysis suggested that the compound exerted its anticancer activities by promoting apoptosis through the inhibition of the oncogenic protein Akt, thereby increasing the expression of poly (ADP-ribose) polymerase (PARP) protein. These results suggest that methyl-3α,23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat is the anticancer compound found in G. celebica, providing a basis for its potential use in cancer disease management. PMID:26870339

  7. Use of in vitro assays to assess the potential antiproliferative and cytotoxic effects of saffron (Crocus sativus L. in human lung cancer cell line

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    Saeed Samarghandian

    2010-01-01

    Full Text Available Background: Saffron is harvested from the dried, dark red stigmas of Crocus sativus flowers. It is used as a spice for flavoring and coloring food as a perfume. It is often used for treating several diseases. We investigated the potential of the ethanolic extract of saffron to induce antiproliferative and cytotoxic effects in cultured carcinomic human alveolar basal epithelial cells in comparison with non-malignant (L929 cells. Materials and Methods: Both cells were cultured in Dulbecco′s modified Eagle′s medium and treated with the ethanolic extract of saffron at various concentrations for two consecutive days. Our study resulted in sequences of events marked by apoptosis, such as loss of cell viability, morphology changes that were evaluated by MTT assay and invert-microscope, respectively. Results: The results showed that the ethanolic extract of saffron decreased cell viability in malignant cells as a concentration and time-dependent manner. The IC 50 values against the lung cancer cell line were determined as 1500 and 565 μg/ml after 24 and 48 h, respectively. However, the extract at different concentrations could not significantly decrease the cell viability in L929 cells. Morphology of MCF7 cells treated with the ethanolic extract confirmed the MTT results. Conclusion: We also showed that even higher concentrations of saffron is safe for L929, but the extract exerts pro-apoptotic effects in a lung cancer-derived cell line and could be considered as a potential chemotherapeutic agent in lung cancer.

  8. Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Zwe-Ling, E-mail: kongzl@mail.ntou.edu.tw; Chang, Jenq-Sheng; Chang, Ke Liang B. [National Taiwan Ocean University, Department of Food Science (China)

    2013-09-15

    Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

  9. Antiproliferative and Apoptotic Effects Triggered by Grape Seed Extract (GSE versus Epigallocatechin and Procyanidins on Colon Cancer Cell Lines

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    Simona Dinicola

    2012-01-01

    Full Text Available Grape seed extract has been proven to exert anticancer effects on different tumors. These effects are mainly ascribed to catechin and procyanidin content. Analytical studies demonstrated that grape seed extract composition is complex and it is likely other components could exert biological activities. Using cell count and flow cytometry assays, we evaluated the cytostatic and apoptotic effects produced by three different grape seed extracts from Italia, Palieri and Red Globe cultivars, on Caco2 and HCT-8 colon cancer cells. These effects were compared to those induced by epigallocatechin and procyanidins, alone or in association, on the same cell lines. All the extracts induced growth inhibition and apoptosis in Caco2 and HCT-8 cells, along the intrinsic apoptotic pathway. On both cell lines, growth inhibition induced by Italia and Palieri grape seed extracts was significantly higher than that it has been recorded with epigallocatechin, procyanidins and their association. In Caco2 cells, the extract from Red Globe cultivar was less effective in inducing growth inhibition than procyanidins alone and in association with epigallocatechin, whereas, in HCT-8 cells, only the association of epigallocatechin and procyanidins triggers a significant proliferation decrease. On both cell lines, apoptosis induced by Italia, Palieri and Red Globe grape seed extracts was considerably higher than has been recorded with epigallocatechin, procyanidins and their association. These data support the hypothesis by which other compounds, present in the grape seed extracts, are likely to enhance the anticancer effects.

  10. Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

    Science.gov (United States)

    Łączkowski, Krzysztof Z.; Świtalska, Marta; Baranowska-Łączkowska, Angelika; Plech, Tomasz; Paneth, Agata; Misiura, Konrad; Wietrzyk, Joanna; Czaplińska, Barbara; Mrozek-Wilczkiewicz, Anna; Malarz, Katarzyna; Musioł, Robert; Grela, Izabela

    2016-09-01

    Synthesis, characterization and investigation of antiproliferative activity of ten thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, MCF-7 and HCT116) and normal mouse fibroblast (BALB/3T3) is presented. The structures of novel compounds were determined using 1H and 13C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 5b, 5c, 5e, 5f and 5i were found to exhibit high activity against human leukaemia MV4-11 cells with IC50 values of 2.17-4.26 μg/ml. The cytotoxic activity of compound 5c and 5f against BALB/3T3 cells is up to 20 times lower than against cancer cell lines. Our results also show that compounds 5e and 5i have very strong activity against MCF-7 and HCT116 with IC50 values of 3.02-4.13 μg/ml. Moreover, spectroscopic characterization and cellular localization for selected compound were performed. In order to identify potential drug targets we perform computer simulations with DNA-binding site of hTopoI and hTopoII and quantum chemical calculation of interaction and binding energies in complexes of the five most active compounds with guanine.

  11. CD34+ cells cultured in stem cell factor and interleukin-2 generate CD56+ cells with antiproliferative effects on tumor cell lines

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    Hensel Nancy

    2005-04-01

    Full Text Available Abstract In vitro stimulation of CD34+ cells with IL-2 induces NK cell differentiation. In order to define the stages of NK cell development, which influence their generation from CD34 cells, we cultured G-CSF mobilized peripheral blood CD34+ cells in the presence of stem cell factor and IL-2. After three weeks culture we found a diversity of CD56+ subsets which possessed granzyme A, but lacked the cytotoxic apparatus required for classical NK-like cytotoxicity. However, these CD56+ cells had the unusual property of inhibiting proliferation of K562 and P815 cell lines in a cell-contact dependent fashion.

  12. Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa on human glioma and neuroblastoma cell lines.

    Science.gov (United States)

    García Prado, E; García Gimenez, M D; De la Puerta Vázquez, R; Espartero Sánchez, J L; Sáenz Rodríguez, M T

    2007-04-01

    Uncaria tomentosa inner bark extract is a popular plant remedy used in folk medicine to treat tumor and inflammatory processes. In this study, the anti-tumoral effects of its pentacyclic alkaloid mitraphylline were investigated. Furthermore, its growth-inhibitory and cytotoxic effects on glioma GAMG and neuroblastoma SKN-BE(2) cell lines were studied using cyclophosphamide and vincristine as controls. A colter counter was used to determine viable cell numbers, followed by application of the tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)2-(4-sulfophenyl)-2H-tetrazolium], inner salt, colorimetric method to evaluate cell viability in this cytotoxicity assay. Micromolar concentrations of mitraphylline (from 5 to 40 microM) inhibited the growth of both cell lines. It inhibited the growth of the two cell lines studied in a dose-dependent manner. The IC(50) values were 12.3 microM (30h) for SKN-BE(2) and 20 microM (48 h) for GAMG, respectively. This action suggests that mitraphylline is a new and promising agent in the treatment of human neuroblastoma and glioma.

  13. Anti-proliferative effect of a compound isolated from Cassia auriculata against human colon cancer cell line HCT 15.

    Science.gov (United States)

    Esakkirajan, M; Prabhu, N M; Arulvasu, C; Beulaja, M; Manikandan, R; Thiagarajan, R; Govindaraju, K; Prabhu, D; Dinesh, D; Babu, G; Dhanasekaran, G

    2014-01-01

    The compound was isolated from leaves of Cassia auriculata and its structure was characterized using high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), UV-vis spectroscopy (UV-vis), fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cytotoxicity, nuclear morphology and lactate dehydrogenase assay of isolated compound was tested against human colon cancer cell line HCT 15. The isolated compound, 4-(4-chlorobenzyl)-2,3,4,5,6,7-hexahydro-7-(2-ethoxyphenyl)benzo[h][1,4,7]triazecin-8(1H)-one at 25μg/ml concentration and by 48h showed 50% inhibition of human colon cancer cells (HCT 15). The results suggest that isolated compound from C. auriculata has potential to prevent colon cancer cell line.

  14. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    Science.gov (United States)

    K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

    2016-05-01

    Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  15. Anti-Proliferative Activity of Meroditerpenoids Isolated from the Brown Alga Stypopodium flabelliforme against Several Cancer Cell Lines

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    Patricia Valentao

    2011-05-01

    Full Text Available The sea constitutes one of the most promising sources of novel compounds with potential application in human therapeutics. In particular, algae have proved to be an interesting source of new bioactive compounds. In this work, six meroditerpenoids (epitaondiol, epitaondiol diacetate, epitaondiol monoacetate, stypotriol triacetate, 14-ketostypodiol diacetate and stypodiol isolated from the brown alga Stypopodium flabelliforme were tested for their cell proliferation inhibitory activity in five cell lines. Cell lines tested included human colon adenocarcinoma (Caco-2, human neuroblastoma (SH-SY5Y, rat basophilic leukemia (RBL-2H3, murine macrophages (RAW.267 and Chinese hamster fibroblasts (V79. Antimicrobial activity of the compounds was also evaluated against Staphylococcus aureus, Salmonella typhimurium, Proteus mirabilis, Bacillus cereus, Enterococcus faecalis and Micrococcus luteus. Overall, the compounds showed good activity against all cell lines, with SH-SY5Y and RAW.267 being the most susceptible. Antimicrobial capacity was observed for epitaondiol monoacetate, stypotriol triacetate and stypodiol, with the first being the most active. The results suggest that these molecules deserve further studies in order to evaluate their potential as therapeutic agents.

  16. Induction of Apoptotic Effects of Antiproliferative Protein from the Seeds of Borreria hispida on Lung Cancer (A549 and Cervical Cancer (HeLa Cell Lines

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    S. Rupachandra

    2014-01-01

    Full Text Available A 35 KDa protein referred to as F3 was purified from the seeds of Borreria hispida by precipitation with 80% ammonium sulphate and gel filtration on Sephadex G-100 column. RP-HPLC analysis of protein fraction (F3 on an analytical C-18 column produced a single peak, detected at 220 nm. F3 showed an apparent molecular weight of 35 KDa by SDS PAGE and MALDI-TOF-MS analyses. Peptide mass fingerprinting analysis of F3 showed the closest homology with the sequence of 1-aminocyclopropane-1-carboxylate deaminase of Pyrococcus horikoshii. The protein (F3 exhibited significant cytotoxic activity against lung (A549 and cervical (HeLa cancer cells in a dose-dependent manner at concentrations ranging from 10 µg to 1000 µg/mL, as revealed by the MTT assay. Cell cycle analysis revealed the increased growth of sub-G0 population in both cell lines exposed to a concentration of 1000 µg/mL of protein fraction F3 as examined from flow cytometry. This is the first report of a protein from the seeds of Borreria hispida with antiproliferative and apoptotic activity in lung (A549 and cervical (HeLa cancer cells.

  17. Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line.

    Science.gov (United States)

    Zanette, Caterina; Pelin, Marco; Crosera, Matteo; Adami, Gianpiero; Bovenzi, Massimo; Larese, Francesca Filon; Florio, Chiara

    2011-08-01

    For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products designed to come in direct contact with the skin. In this study we investigated the effects of Ag NPs on skin using the human-derived keratinocyte HaCaT cell line model. Ag NPs caused a concentration- and time-dependent decrease of cell viability, with IC(50) values of 6.8 ± 1.3 μM (MTT assay) and 12 ± 1.2 μM (SRB assay) after 7 days of contact. A 24h treatment, followed by a 6 day recovery period in Ag NPs-free medium, reduced cell viability with almost the same potency (IC(50)s of 15.3 ± 4.6 and 35 ± 20 μM, MTT and SRB assays, respectively). Under these conditions, no evidence of induction of necrotic events (propidium iodide assay) was found. Apocynin, NADPH-oxidase inhibitor, or N(G)-monomethyl-L-argynine, nitric oxide synthase inhibitor, did not prevent NPs-induced reduction of cell viability. TEM analysis of cells exposed to NPs for 24h revealed alteration of nuclear morphology but only a marginal presence of individual NPs inside the cells. These results demonstrate that on HaCaT keratinocytes a relatively short time of contact with Ag NPs causes a long-lasting inhibition of cell growth, not associated with consistent Ag NPs internalization.

  18. Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines

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    Faten Merhi

    2008-08-01

    Full Text Available Faten Merhi1, Jacques Auger2, Francine Rendu1, Brigitte Bauvois11UMR 7131 UPMC Paris Universitas/CNRS, Groupe Hospitalier Broussais-HEGP, Paris, France; 2University F. Rabelais, IRBI, UPRESA CNRS 6035, Tours, FranceAbstract: Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS, diallyl TS (All2TS, dipropyl TS (Pr2TS and dimethyl TS (Me2TS, are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6 in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide. As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr2TS and Me2TS, but not All2TS and sulfides, 1 inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2 induced macrophage maturation, and 3 inhibited the levels of secreted MMP-9 (protein and activity and TNF-α protein, without altering mRNA levels. By establishing for the first time that Pr2TS and Me2TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.Keywords: acute myeloid leukemia, thiosulfinate, proliferation, differentiation, matrix metalloproteinase-9

  19. Bioassay-Guided Fractionation and In Vitro Antiproliferative Effects of Fractions of Artemisia nilagirica on THP-1 cell line.

    Science.gov (United States)

    Gul, Mir Zahoor; Chandrasekaran, Sambamurthy; K, Manjulatha; Bhat, Mohd Yasin; Maurya, Radheshyam; Qureshi, Insaf Ahmed; Ghazi, Irfan Ahmad

    2016-10-01

    ABSTACT Artemisia nilagirica (Clarke) is a widely used medicinal herb in Indian traditional system of medicine. Therefore, the present study was designed to evaluate the effects of A. nilagirica extracts/fractions on inhibition of proliferation and apoptosis in a human monocytic leukemia (THP-1) cell line. The crude extracts (A. nilagirica ethyl acetate extract [ANE] and A. nilagirica methanolic extract [ANA]) showed cytotoxic activity toward THP-1 cells with the IC50 values of 38.21 ± 7.37 and 132.41 ± 7.19 µg/ml, respectively. However, the cytotoxic activity of active fractions (ANE-B and ANM-9) obtained after column chromatography was found to be much more pronounced than their parent extracts. The IC50 values of ANE-B and ANM-9 were found to be 27.04 ± 2.54 µg/ml and 12.70 ± 4.79 µg/ml, respectively, suggesting greater susceptibility of the malignant cells. Cell cycle analysis and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) assay revealed that inhibition of cell growth by A. nilagirica fractions on THP-1 cells was mediated by apoptosis. Active fractions of A. nilagirica increased the expression levels of caspase-3, -7, and poly-ADP-ribose polymerase (PARP), a critical member of the apoptotic pathway. These results suggested that active fractions of A. nilagirica may play a promising role in growth suppression by inducing apoptosis in human monocytic leukemic cells via mitochondria-dependent and death receptor-dependent apoptotic pathways. PMID:27618154

  20. Antiproliferative effect of a synthetic aptamer mimicking androgen response elements in the LNCaP cell line.

    Science.gov (United States)

    Kouhpayeh, S; Einizadeh, A R; Hejazi, Z; Boshtam, M; Shariati, L; Mirian, M; Darzi, L; Sojoudi, M; Khanahmad, H; Rezaei, A

    2016-08-01

    Prostate cancer usually develops to a hormone-refractory state that is irresponsive to conventional therapeutic approaches. Therefore, new methods for treating aggressive prostate cancer are under development. Because of the importance of androgen receptors (ARs) in the development of the hormone-refractory state and AR mechanism of action, this study was designed. A single-stranded DNA as an aptamer was designed that could mimic the hormone response element (HRE). The LNCaP cells as an AR-rich model were divided into three sets of triplicate groups: the test group was transfected with Aptamer Mimicking HRE (AMH), Mock received only transfection reagents (mock) and a negative control. All three sets received 0, 10 and 100 nM of dehydroepiandrosterone (DHEA) separately. Data analysis showed hormone dependency of LNCaP cells in the negative control group upon treatment with 10 and 100 nM DHEA (compared with cells left untreated (P=0.001)). Transfection of AMH resulted in significant reduction of proliferation in the test group when compared with the negative control group with 10 (P=0.001) or 100 nM DHEA (P=0.02). AMH can form a hairpin structure at 37 °C and mimic the genomic HRE. Hence, it is capable of effectively competing with genomic HRE and interrupting the androgen signaling pathway in a prostate cancer cell line (LNCaP). PMID:27364573

  1. Antiproliferative Properties of Oleuropein in Human Osteosarcoma Cells.

    Science.gov (United States)

    Morana, Jose M; Leal-Hernande, Olga; Canal-Macías, Maria L; Roncero-Martin, Raul; Guerrero-Bonmatty, Rafael; Aliaga, Ignacio; Zamorano, Juan D Pedrera

    2016-04-01

    In this study, we evaluated the antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) of oleuropein, an olive oil compound traditionally found in the Mediterranean diet. Oleuropein exhibited obvious cytotoxic effects on human osteosarcoma cells in a concentration- and time-dependent manner. Statistical analysis of IC50 by the Probit regression method suggested that oleuropein had similar toxic effects on both cell lines tested (IC50 range from 247.4-475.0 µM for MG63 cells and from 798.7-359.9 µM for Saos2 cells). PMID:27396201

  2. Analysis of the Antiproliferative Effects of Curcumin and Nanocurcumin in MDA-MB231 as a Breast Cancer Cell Line.

    Science.gov (United States)

    Khosropanah, Mohammad Hossein; Dinarvand, Amin; Nezhadhosseini, Afsaneh; Haghighi, Alireza; Hashemi, Sima; Nirouzad, Fereidon; Khatamsaz, Sepideh; Entezari, Maliheh; Hashemi, Mehrdad; Dehghani, Hossein

    2016-01-01

    Cancer is one of the main causes of mortality in the world which appears by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identification of new cytotoxic drug with low sid effects on immune system has developed as important area in new studies of immunopharmacology. Curcumin is a natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility and bioavailability, hence the need for suitable carriers. In this report we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan (MA-chitosan) nanogels were prepared by the technique of self-assembly. Curcumin was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in vitro cytotoxic activity of cell death of curcumin and nanocurcumin on human breast adenocarcinoma cell line (MDA-MB231). Cytotoxicity and viability of curcumin and nanocurcumin were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MDA-MB231 cells was significantly inhibited by curcumin and nanocurcumin in a concentration-dependent manner in defined times. There were significant differences in IC50 curcumin and nanocurcumin. curcumin -loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of curcumin -loaded nanoparticles. PMID:27610163

  3. Umbelliprenin is cytotoxic against QU-DB large cell lung cancer cell line but anti-proliferative against A549 adenocarcinoma cells

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    Khaghanzadeh Narges

    2012-10-01

    Full Text Available Abstract Background Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researchers' attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer. Methods The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells, and propidium iodide (for necrotic cells dyes were employed. Results Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and less concentrations of umbelliprenin, no suppressive effect was observed. Conclusions We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

  4. Umbelliprenin is Cytotoxic against QU-DB Large Cell Lung Cancer Cell Line but Anti-Proliferative against A549 Adenocarcinoma Cells

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    Abbas Ghaderi

    2012-10-01

    Full Text Available Background:Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins.Recently, umbelliprenin has attracted the researchers' attention for its antitumor activitiesagainst skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer.Methods:The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells, and propidium iodide (for necrotic cells dyes were employed.Results:Data from three independent MTT experiments in triplicate revealed that IC50 values for QUDB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells,but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and lessconcentrations of umbelliprenin, no suppressive effect was observed.Conclusions:We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

  5. Proapoptotic and Antiproliferative Effects of Thymus caramanicus on Human Breast Cancer Cell Line (MCF-7 and Its Interaction with Anticancer Drug Vincristine

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    Saeed Esmaeili-Mahani

    2014-01-01

    Full Text Available Thymus caramanicus Jalas is one of the species of thymus that grows in the wild in different regions of Iran. Traditionally, leaves of this plant are used in the treatment of diabetes, arthritis, and cancerous situation. Therefore, the present study was designed to investigate the selective cytotoxic and antiproliferative properties of Thymus caramanicus extract (TCE. MCF-7 human breast cancer cells were used in this study. Cytotoxicity of the extract was determined using MTT and neutral red assays. Biochemical markers of apoptosis (caspase 3, Bax, and Bcl-2 and cell proliferation (cyclin D1 were evaluated by immunoblotting. Vincristine was used as anticancer control drug in extract combination therapy. The data showed that incubation of cells with TCE (200 and 250 μg/mL significantly increased cell damage, activated caspase 3 and Bax/Bcl2 ratio. In addition, cyclin D1 was significantly decreased in TCE-treated cells. Furthermore, concomitant treatment of cells with extract and anticancer drug produced a significant cytotoxic effect as compared to extract or drugs alone. In conclusion, thymus extract has a potential proapoptotic/antiproliferative property against human breast cancer cells and its combination with chemotherapeutic agent vincristine may induce cell death effectively and be a potent modality to treat this type of cancer.

  6. Antiproliferative and apoptotic effect of Pleurotus ostreatus on human mammary carcinoma cell line (michigan cancer foundation-7

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    Krishnamoorthy Deepalakshmi

    2016-01-01

    Conclusion: The study demonstrates a potent anticancer property of P. ostreatus against human mammary carcinoma cells which might be of value in nutraceutical industry. Further investigations are essential to establish it as a treatment against breast cancer.

  7. In vitro antiproliferative and apoptosis-inducing properties of a mononuclear copper(II) complex with dppz ligand, in two genotypically different breast cancer cell lines.

    Science.gov (United States)

    Dhivya, Rajakumar; Jaividhya, Paramasivam; Riyasdeen, Anvarbatcha; Palaniandavar, Mallayan; Mathan, Ganeshan; Akbarsha, Mohammad Abdulkader

    2015-10-01

    In the background that there is concerted effort to discover newer metal-based cancer chemotherapeutic agents that could overcome the limitations in cisplatin and that copper, a biocompatible and redox-active metal, offers potential as alternative to cisplatin, the present study was undertaken to investigate the in vitro anti-proliferative properties of the mononuclear copper(II)complex [Cu(L)(diimine)] + where LH = 2-[(2-dimethylaminoethylimino)methyl]phenol and diimine = dipyrido[3,2-a:2',3'-c]phenazine (dppz) using breast cancer cell lines MCF-7 (ER(+ve) and p53(WT)) and MDA-MB-231(ER(-ve) and p53(mutant)) when cisplatin was used as positive control. The complex affected the viability of both the cell lines in dose-as well as duration-dependent manner as revealed in the MTT assay. The 24 and 48 h IC50 of the complex were several times lesser than those of cisplatin, and within this huge difference the efficacy of the complex was much superior with MCF-7 cell compared to MDA-MB-231 cell. The cell death was preferentially apoptosis, though necrosis also occurred to a certain extent. These inferences were substantiated by AO/EB fluorescent staining, Hoechst staining, assessment of mitochondrial transmembrane potential, comet assay for DNA damage, DCFH assay for reactive oxygen species (ROS) generation and Western blot of apoptosis-related proteins. Thus, the copper(II) dppz complex under investigation is much more efficient than cisplatin in affecting viability of the breast cancer cells. The underlying mechanism appears to be DNA damage-primed (in view of the known intercalation mode of binding of the complex with DNA) and ROS-associated mitochondria-mediated intrinsic apoptosis to a great extent but necrosis also has a role to a certain extent, which may also be a PARP-mediated cell death independent of apoptosis. Within the purview of this conclusion, the results indicate that the ER and/or p53 genotypes have a bearing on the efficacy of the complex as a

  8. Apoptosis mediated anti-proliferative effect of compound isolated from Cassia auriculata leaves against human colon cancer cell line

    Science.gov (United States)

    Esakkirajan, M.; Prabhu, N. M.; Manikandan, R.; Beulaja, M.; Prabhu, D.; Govindaraju, K.; Thiagarajan, R.; Arulvasu, C.; Dhanasekaran, G.; Dinesh, D.; Babu, G.

    2014-06-01

    A compound was isolated from Cassia auriculata leaves and characterized by high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), UV-vis spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). The in vitro anticancer effect of the compound isolated from C. auriculata was evaluated in human colon cancer cells HCT 15 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cytotoxicity, nuclear morphology analysis and measurement of lactate dehydrogenase. The isolated compound 4-(2,5 dichlorobenzyl)-2,3,4,5,6,7 hexahydro7(4 methoxyphenyl)benzo[h][1,4,7] triazecin8(1H)-one showed 50% inhibition of HCT 15 cells when tested at 20 μg/ml after 24 h incubation. Cytotoxicity, nuclear morphology and lactate dehydrogenase assays clearly show potent anticancer activity of the isolated compound against colon cancer. Thus, the in vitro findings suggest that the compound isolated from C. auriculata leaves have potent anti-cancer properties with possible clinical applications.

  9. Molecular mechanisms of antiproliferative effects induced by Schisandra-derived dibenzocyclooctadiene lignans (+)-deoxyschisandrin and (-)-gomisin N in human tumour cell lines.

    Science.gov (United States)

    Casarin, Elisabetta; Dall'Acqua, Stefano; Smejkal, Karel; Slapetová, Tereza; Innocenti, Gabbriella; Carrara, Maria

    2014-10-01

    A different behavior of the two dibenzocyclooctadiene lignans (+)-deoxyschisandrin (1) and (-)-gomisin N (2), from Schisandra chinensis fruits, was observed against two human tumour cell lines, (2008 and LoVo). These lignans inhibited cell growth in a dose-dependent manner on both cell lines, but inducing different types of cell death. In particular, (+)-deoxyschisandrin (1) caused apoptosis in colon adenocarcinoma cells (LoVo) but not in ovarian adenocarcinoma cells (2008), while (-)-gomisin N (2) induced apoptosis on both the cell lines used. Mitochondrial-mediated pathway was not involved in apoptotic stimuli. Both compounds caused G2/M phase cell growth arrest correlated with tubulin polymerization.

  10. Antiproliferative effect from sesquiterpene lactone s of Carpesium rosulatum MlQ consumed in South Korea on the five human cancer cell lines

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    Hyung-In Moon

    2010-07-01

    Full Text Available In search for antiproliferative compound against human cancer cells (A549, SK-OV-3, SK-MEL-2, XF498, HCT15, a chloroform soluble extract obtained by re-extraction of the methanol extract of whole plant of Carpesium rosulatum MlQ. (Compositae exhibited cytotoxic activity. Four germacrane sesquiterpene lactones 2α,5-epoxy-5,10-dihydroxy-6-angeloyl-oxy-9β-isobutyloxy-germacran-8α,12-olide, 2α,5-epoxy-5,10-dihydroxy-6α,9β-diangeloyloxy-germacran-8α,12-olide, 2α,5-epoxy-5,10-dihydroxy-6α-angeloyloxy-9β-(3-methyl-butanoyloxy-germacran-8α,12-olide, and 2β,5-epoxy-5,10-dihydroxy-6α,9β-diangeloyloxy-germacran-8α,12-olide were isolated from the chloroform extract of C . rosulatum, and 2α,5-epoxy-5,10-dihydroxy-6α,9β-diangeloyloxy-germacran-8α,12-olide showed the most potent cytotoxicity with IC 50 value of 6.01 μM against SK-MEL-2 .

  11. Anti-proliferative and apoptosis-triggering potential of disulfiram and disulfiram-loaded polysorbate 80-stabilized PLGA nanoparticles on hepatocellular carcinoma Hep3B cell line.

    Science.gov (United States)

    Hoda, Muddasarul; Pajaniradje, Sankar; Shakya, Garima; Mohankumar, Kumaravel; Rajagopalan, Rukkumani

    2016-08-01

    There is an emerging trend to restudy known drugs for their anti-cancer potential. One such anti-alcoholic drug, disulfiram, with significant anti-cancer potential was studied for its efficacy against Hep3B cell lines, an in vitro model of hepatocellular carcinoma. Simultaneously, we intended to study the effect of polysorbate 80-stabilized PLGA nanoparticles and its DSF-loaded counterpart. Cell and nuclear staining, comet assay, flow cytometry and Western blots were performed. Results suggest that cell proliferation was inhibited by DSF and its PLGA nanoparticles through cell cycle arrest, triggering activation of apoptotic pathways that culminates with cell death. DSF loaded nanoparticles when compared with free DSF, showed significantly lesser effect due to its sustained drug-releasing property, while empty nanoparticles showed negligible influence on Hep3B cells. Our results suggest that DSF alone contributes to cell death, while polysorbate 80-stabilized PLGA nanoparticles show sustained drug release patterns that would potentially lower dosage regimens. PMID:27013133

  12. Anti-proliferative effect of fungal taxol extracted from Cladosporium oxysporum against human pathogenic bacteria and human colon cancer cell line HCT 15

    Science.gov (United States)

    Gokul Raj, K.; Manikandan, R.; Arulvasu, C.; Pandi, M.

    2015-03-01

    Cladosporium oxysporum a new taxol producing endophytic fungus was identified and production of taxol were characterized using UV-visible spectroscopy (UV-vis), high-performance liquid chromatography (HPLC), infrared (IR) nuclear magnetic resonance spectroscopy (NMR (13C and 1H)) and liquid chromatography-mass spectrometry (LC-MS). The taxol biosynthetic gene (dbat) was evaluated for new taxol producing fungus. Antibacterial activity against six different human pathogenic bacteria was done by agar well diffusion method. The anticancer efficacy of isolated fungal taxol were also evaluated in human colon cancer cell HCT 15 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cytotoxicity and nuclear morphology analysis. The isolated fungal taxol showed positive towards biosynthetic gene (dbat) and effective against both Gram positive as well as Gram negative. The fungal taxol suppress growth of cancer cell line HCT 15 with an IC50 value of 3.5 μM concentration by 24 h treatment. Thus, the result reveals that C. oxysporum could be a potential alternative source for production of taxol and have antibacterial as well as anticancer properties with possible clinical applications.

  13. Antiproliferative effect of isolated isoquinoline alkaloid from Mucuna pruriens seeds in hepatic carcinoma cells.

    Science.gov (United States)

    Kumar, Pranesh; Rawat, Atul; Keshari, Amit K; Singh, Ashok K; Maity, Siddhartha; De, Arnab; Samanta, Amalesh; Saha, Sudipta

    2016-01-01

    The present study was undertaken to investigate the antiproliferative action of isolated M1 (6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) from Mucuna pruriens seeds using human hepatic carcinoma cell line (Huh-7 cells). Initially, docking studies was performed to find out the binding affinities of M1 to caspase-3 and 8 enzymes. Later, cytotoxic action of M1 was measured by cell growth inhibition (MTT), followed by caspase-3 and 8 enzymes assay colorimetrically. Our results collectively suggested that M1 had strong binding affinity to caspase-8 in molecular modelling. M1 possessed antiproliferative activity on Huh-7 cells (EC50 = 13.97 μM) and also inhibited the action of caspase-8 enzyme, signified process of apoptosis. M1 was active against Huh-7 cells that may be useful for future hepatic cancer treatment. PMID:25774560

  14. New steroidal 17β-carboxy derivatives present anti-5α-reductase activity and anti-proliferative effects in a human androgen-responsive prostate cancer cell line.

    Science.gov (United States)

    Amaral, Cristina; Varela, Carla; Correia-da-Silva, Georgina; Tavares da Silva, Elisiário; Carvalho, Rui A; Costa, Saul C P; Cunha, Sara C; Fernandes, José O; Teixeira, Natércia; Roleira, Fernanda M F

    2013-11-01

    The androgens testosterone (T) and dihydrotestosterone (DHT), besides playing an important role in prostate development and growth, are also responsible for the development and progression of benign prostate hyperplasia (BPH) and prostate cancer. Therefore, the actions of these hormones can be antagonized by preventing the irreversible conversion of T into DHT by inhibiting 5α-reductase (5α-R). This has been a useful therapeutic approach for the referred diseases and can be achieved by using 5α-reductase inhibitors (RIs). Steroidal RIs, finasteride and dutasteride, are used in clinic for BPH treatment and were also proposed for chemoprevention of prostate cancer. Nevertheless, due to the increase in bone and muscle loss, impotency and occurrence of high-grade prostate tumours, it is important to seek for other potent and specific molecules with lower side effects. In the present work, we designed and synthesized steroids with the 3-keto-Δ(4) moiety in the A-ring, as in the 5α-R substrate T, and with carboxamide, carboxyester or carboxylic acid functions at the C-17β position. The inhibitory 5α-R activity, in human prostate microsomes, as well as the anti-proliferative effects of the most potent compounds, in a human androgen-responsive prostate cancer cell line (LNCaP cells), were investigated. Our results showed that steroids 3, 4 and 5 are good RIs, which suggest that C-17β lipophylic amides favour 5α-R inhibition. Moreover, these steroids induce a decrease in cell viability of stimulated LNCaP cells, in a 5α-R dependent-manner, similarly to finasteride. PMID:23933094

  15. Antiproliferative study of B. javanica extracts against head and neck cancer cells

    International Nuclear Information System (INIS)

    Brucea javanica or locally known as Meladapahit, are being used in Malaysia as traditional medicine mainly for the treatment of diabetes mellitus and hypertension. In order to study the potential use of this plant for cancer treatment, we have prepared crude extracts of the leaves and fruits, and assessed them for antiproliferative activities against head and neck cancer cell line which is HTB-43. The dried and ground leaves and fruits of the plant were successively extracted using hexane, chloroform, methanol and water, respectively. Inhibition of growth of the cultured cancer cells line was measured using a standard Micro culture Tetrazolium Technique (MTT) assay. The crude extracts were also subjected to toxicity test using brine shrimp lethality assay. Most of the tested crude extracts exhibited significant antiproliferative activities against the HTB-43 cell with IC50 ranging from 8.46 μg/ml to 47.25 μg/ml. The chloroform extract from the leaves gave the highest antiproliferative activity (IC50, 8.46 μg/ml). Hexane extract from the fruits, aqueous and hexane extracts from B. javanica leaves showed low antiproliferative activities to the HTB-43 cell line with an IC50 values >100 μg/ml. The chloroform extracts from fruits and leaves and methanol extract from fruits induced toxicity against brine shrimps with LC50 values of 118.7 μg/ml, 512.44 μg/ml and 75.27 μg/ml respectively. It indicated that bioactive components presence in the crude extracts for its pharmacologic effects against head and neck cancer cells. Methanolic extract of Brucea javanica fruit was selected as the most effective extract to inhibit the growth of head and neck cancer cells (HTB-43) by the two different assays used. (author)

  16. In vitro assessment of antiproliferative action selectivity of dietary isothiocyanates for tumor versus normal human cells

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    Konić-Ristić Aleksandra

    2016-01-01

    Full Text Available Background/Aim. Numerous epidemiological studies have shown beneficial effects of cruciferous vegetables consumption in cancer chemoprevention. Biologically active compounds of different Brassicaceae species with antitumor potential are isothiocyanates, present in the form of their precursors - glucosinolates. The aim of this study was to determine the selectivity of antiproliferative action of dietary isothiocyanates for malignant versus normal cells. Methods. Antiproliferative activity of three isothiocyanates abundant in human diet: sulforaphane, benzyl isothiocyanate (BITC and phenylethyl isothiocyanate, on human cervix carcinoma cell line - HeLa, melanoma cell line - Fem-x, and colon cancer cell line - LS 174, and on peripheral blood mononuclear cells (PBMC, with or without mitogen, were determined by MTT colorimetric assay 72 h after their continuous action. Results. All investigated isothiocyanates inhibited the proliferation of HeLa, Fem-x and LS 174 cells. On all cell lines treated, BITC was the most potent inhibitor of cell proliferation with half-maximum inhibitory concentration (IC50 values of 5.04 mmoL m-3 on HeLa cells, 2.76 mmol m-3 on Fem-x, and 14.30 mmol m-3 on LS 174 cells. Antiproliferative effects on human PBMC were with higher IC50 than on malignant cells. Indexes of selectivity, calculated as a ratio between IC50 values obtained on PBMC and malignant cells, were between 1.12 and 16.57, with the highest values obtained for the action of BITC on melanoma Fem-x cells. Conclusion. Based on its antiproliferative effects on malignant cells, as well as the selectivity of the action to malignant vs normal cells, benzyl isothiocyanate can be considered as a promising candidate in cancer chemoprevention. In general, the safety of investigated compounds, in addition to their antitumor potential, should be considered as an important criterion in cancer chemoprevention. Screening of selectivity is a plausible approach to the evaluation

  17. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  18. Antiproliferative effects of some medicinal plants on HeLa cells

    Directory of Open Access Journals (Sweden)

    Cenić-Milošević Desanka

    2013-01-01

    Full Text Available Medicinal plants maintain the health and vitality of individuals, and also have potential curative effect on various diseases, including cancer. In this study were investigated the antiproliferative effects of water extracts of previously obtained ethanolic dry extracts of three different medicinal plants (Echinacea angustifolia, Salvia officinalis and Melissa officinalis on cell lines derived from human cervix adenocarcinoma (HeLa cells. The best cytotoxic activity (IC50 = 43.52 μg/ml on HeLa cell lines was exhibited by Echinacea angustifolia. The extract of Salvia officinalis also showed a good cytotoxic activity against HeLa cell lines; the IC50 value was 70.41 μg/ml. Melissa officinalis manifested a slightly weaker cytotoxic activity and an IC50 value of 122.22 μg/ml. [Projekat Ministarstva nauke Republike Srbije, br. 34021 i br. 175011

  19. Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells

    Science.gov (United States)

    Kilgore, Joshua; Jackson, Amanda L; Clark, Leslie H; Guo, Hui; Zhang, Lu; Jones, Hannah M; Gilliam, Timothy P; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

    2016-01-01

    Objective: Biguanides are anti-diabetic drugs that are thought to have anti-tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines. Methods: The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting. Results: Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 μM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines. Conclusion: Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation. PMID:27398153

  20. Stereospecific ligands and their complexes. Part XII. Synthesis, characterization and in vitro antiproliferative activity of platinum(IV) complexes with some O,O‧-dialkyl esters of (S,S)-ethylenediamine-N,N‧-di-2-propanoic acid against colon cancer (HCT-116) and breast cancer (MDA-MB-231) cell lines

    Science.gov (United States)

    Stojković, Danijela Lj.; Jevtić, Verica V.; Radić, Gordana P.; Đačić, Dragana S.; Ćurčić, Milena G.; Marković, Snežana D.; Ðinović, Vesna M.; Petrović, Vladimir P.; Trifunović, Srećko R.

    2014-03-01

    Synthesis of three new platinum(IV) complexes C1-C3, with bidentate N,N‧-ligand precursors, O,O‧-dialkyl esters (alkyl = propyl, butyl and pentyl), of (S,S)-ethylenediamine-N,N‧-di-2-propanoic acid, H2-S,S-eddp were reported. The reported platinum(IV) complexes characterized by elemental analysis and their structures were discussed on the bases of their infrared, 1H and 13C NMR spectroscopy. In vitro antiproliferative activity was determined on tumor cell lines: human colon carcinoma HCT-116 and human breast carcinoma MDA-MB-231, using MTT test.

  1. Cation-selective transporters are critical to the AMPK-mediated antiproliferative effects of metformin in human breast cancer cells.

    Science.gov (United States)

    Cai, Hao; Zhang, Yunhui; Han, Tianxiang Kevin; Everett, Ruth S; Thakker, Dhiren R

    2016-05-01

    The antidiabetic drug metformin exerts antineoplastic effects against breast cancer and other cancers. One mechanism by which metformin is believed to exert its anticancer effect involves activation of its intracellular target, adenosine monophosphate-activated protein kinase (AMPK), which is also implicated in the antidiabetic effect of metformin. It is proposed that in cancer cells, AMPK activation leads to inhibition of the mammalian target of rapamycin (mTOR) and the downstream pS6K that regulates cell proliferation. Due to its hydrophilic and cationic nature, metformin requires cation-selective transporters to enter cells and activate AMPK. This study demonstrates that expression levels of cation-selective transporters correlate with the antiproliferative and antitumor efficacy of metformin in breast cancer. Metformin uptake and antiproliferative activity were compared between a cation-selective transporter-deficient human breast cancer cell line, BT-20, and a BT-20 cell line that was engineered to overexpress organic cation transporter 3 (OCT3), a representative of cation-selective transporters and a predominant transporter in human breast tumors. Metformin uptake was minimal in BT-20 cells, but increased by >13-fold in OCT3-BT20 cells, and its antiproliferative potency was >4-fold in OCT3-BT20 versus BT-20 cells. This increase in antiproliferative activity was associated with greater AMPK phosphorylation and decreased pS6K phosphorylation in OCT3-BT20 cells. In vitro data were corroborated by in vivo observations of significantly greater antitumor efficacy of metformin in xenograft mice bearing OCT3-overexpressing tumors versus low transporter-expressing wildtype tumors. Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer. PMID:26669511

  2. Cation-selective transporters are critical to the AMPK-mediated antiproliferative effects of metformin in human breast cancer cells.

    Science.gov (United States)

    Cai, Hao; Zhang, Yunhui; Han, Tianxiang Kevin; Everett, Ruth S; Thakker, Dhiren R

    2016-05-01

    The antidiabetic drug metformin exerts antineoplastic effects against breast cancer and other cancers. One mechanism by which metformin is believed to exert its anticancer effect involves activation of its intracellular target, adenosine monophosphate-activated protein kinase (AMPK), which is also implicated in the antidiabetic effect of metformin. It is proposed that in cancer cells, AMPK activation leads to inhibition of the mammalian target of rapamycin (mTOR) and the downstream pS6K that regulates cell proliferation. Due to its hydrophilic and cationic nature, metformin requires cation-selective transporters to enter cells and activate AMPK. This study demonstrates that expression levels of cation-selective transporters correlate with the antiproliferative and antitumor efficacy of metformin in breast cancer. Metformin uptake and antiproliferative activity were compared between a cation-selective transporter-deficient human breast cancer cell line, BT-20, and a BT-20 cell line that was engineered to overexpress organic cation transporter 3 (OCT3), a representative of cation-selective transporters and a predominant transporter in human breast tumors. Metformin uptake was minimal in BT-20 cells, but increased by >13-fold in OCT3-BT20 cells, and its antiproliferative potency was >4-fold in OCT3-BT20 versus BT-20 cells. This increase in antiproliferative activity was associated with greater AMPK phosphorylation and decreased pS6K phosphorylation in OCT3-BT20 cells. In vitro data were corroborated by in vivo observations of significantly greater antitumor efficacy of metformin in xenograft mice bearing OCT3-overexpressing tumors versus low transporter-expressing wildtype tumors. Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer.

  3. New catechol derivatives of safrole and their antiproliferative activity towards breast cancer cells.

    Science.gov (United States)

    Madrid Villegas, Alejandro; Espinoza Catalán, Luis; Montenegro Venegas, Iván; Villena García, Joan; Carrasco Altamirano, Héctor

    2011-06-03

    Catechols were synthesized from safrole. Nine derivatives were prepared and assessed for antiproliferative effects using different human cell lines. The in vitro growth inhibition assay was based on the sulphorhodamine dye to quantify cell viability. The derivatives 4-allylbenzene-1,2-diol (3), 4 4-[3-(acetyloxy)propyl]-1,2-phenylene diacetate (6) and 4-[3-(acetyloxy)propyl]-5-nitro-1,2-phenylene diacetate (10) showed higher cytotoxicity than the parent compound 2 in tests performed on two breast cancer cell lines (MCF-7 and MDA-MB-231). The IC₅₀ values of 40.2 ± 6.9 μM, 5.9 ± 0.8 μM and 33.8 ± 4.9 μM, respectively, were obtained without toxicity towards dermal human fibroblast (DHF cells).

  4. New Catechol Derivatives of Safrole and Their Antiproliferative Activity towards Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Héctor Carrasco Altamirano

    2011-06-01

    Full Text Available Catechols were synthesized from safrole. Nine derivatives were prepared and assessed for antiproliferative effects using different human cell lines. The in vitro growth inhibition assay was based on the sulphorhodamine dye to quantify cell viability. The derivatives 4-allylbenzene-1,2-diol (3, 4 4-[3-(acetyloxypropyl]-1,2-phenylene diacetate (6 and 4-[3-(acetyloxypropyl]-5-nitro-1,2-phenylene diacetate (10 showed higher cytotoxicity than the parent compound 2 in tests performed on two breast cancer cell lines (MCF-7 and MDA-MB-231. The IC50 values of 40.2 ± 6.9 μM, 5.9 ± 0.8 μM and 33.8 ± 4.9 μM, respectively, were obtained without toxicity towards dermal human fibroblast (DHF cells.

  5. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    Science.gov (United States)

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.

  6. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    Science.gov (United States)

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract. PMID:27071804

  7. Blockade of sonic hedgehog signal pathway enhances antiproliferative effect of EGFR inhibitor in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Wei-guo HU; Tao LIU; Jiong-xin XIONG; Chun-you WANG

    2007-01-01

    Aim: To investigate the expression of sonic hedgehog (SHH) and epidermal growth factor receptor (EGFR) signal molecules in pancreatic cancer cells, and to assess the inhibitory effects through the blockade of the SHH and EGFR signaling path- ways by cyclopamine and Iressa, respectively. Methods: The expression of SHH and EGFR in pancreatic cancer cell lines (PANC-1, SUIT-2, and ASPC-1) was de-tected by RT-PCR and Western blot analysis. After treatment with different con-centrations of cyclopamine, alone or in combination with Iressa, the antiproliferative effect on pancreatic cancer cells was analyzed by methyl thiazolyl tetrazolium assays. A flow cytometry analysis was used to detect the cellular cycle distribu-tion and apoptosis of pancreatic cancer cells. Results: All of the 3 pancreatic cancer cell lines expressed SHH, Smoothened (SMO), and EGFR. Cyclopamine could downregulate the expression of EGFR in all cell lines. Cyclopamine or Iressa could induce a growth inhibitory effect in a dose-dependent manner. Moreover,the combined use of 2.5 μmol/L cyclopamine and 1 μmol/L Iressa induced an enhanced inhibitory effect and a greater apoptosis rate than any agent alone. The percentage of the cell population of the G0/G1 and sub-G1 phases was significantly increased along with the increasing dose of cyclopamine and/or Iressa. Conclusion: The blockade of the sonic hedgehog signal pathway enhances the antiproliferative effect of the EGFR inhibitor through the downregulation of its expression in pancreatic cancer cells. The simultaneous blockade of SHH and EGFR signaling represents possible targets of new treatment strategies for pan-creatic carcinoma.

  8. Furanodiene presents synergistic anti-proliferative activity with paclitaxel via altering cell cycle and integrin signaling in 95-D lung cancer cells.

    Science.gov (United States)

    Xu, Wen-Shan; Dang, Yuan-Ye; Chen, Xiu-Ping; Lu, Jin-Jian; Wang, Yi-Tao

    2014-02-01

    Furanodiene (FUR) is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anti-proliferative activities in several cancer cell lines. Recently, we found that the combined treatment of FUR with paclitaxel (TAX) showed synergetic anti-proliferative activities in 95-D lung cancer cells. Herein, we showed that FUR reduced the cell numbers distributed in mitosis phase induced by TAX while increased those in G1 phase. The protein levels of cyclin D1, cyclin B1, CDK6 and c-Myc were all down-regulated in the group of combined treatment. The dramatically down-regulated expression of integrin β4, focal adhesion kinase and paxillin might partially contribute to the synergic effect. Though FUR alone obviously induced endoplasmic reticulum stress, this signaling pathway may not contribute to the synergetic anti-proliferative effect as the protein expression of CHOP and BIP was similar in FUR alone and combined treatment group.

  9. Antiproliferative activity of bicyclic benzimidazole nucleosides: synthesis, DNA-binding and cell cycle analysis.

    Science.gov (United States)

    Sontakke, Vyankat A; Lawande, Pravin P; Kate, Anup N; Khan, Ayesha; Joshi, Rakesh; Kumbhar, Anupa A; Shinde, Vaishali S

    2016-04-26

    An efficient route was developed for synthesis of bicyclic benzimidazole nucleosides from readily available d-glucose. The key reactions were Vörbruggen glycosylation and ring closing metathesis (RCM). Primarily, to understand the mode of DNA binding, we performed a molecular docking study and the binding was found to be in the minor groove region. Based on the proposed binding model, UV-visible and fluorescence spectroscopic techniques using calf thymus DNA (CT-DNA) demonstrated a non-intercalative mode of binding. Antiproliferative activity of nucleosides was tested against MCF-7 and MDA-MB-231 breast cancer cell lines and found to be active at low micromolar concentrations. Compounds and displayed significant antiproliferative activity as compared to and with the reference anticancer drug, doxorubicin. Cell cycle analysis showed that nucleoside induced cell cycle arrest at the S-phase. Confocal microscopy has been performed to validate the induction of cellular apoptosis. Based on these findings, such modified bicyclic benzimidazole nucleosides will make a significant contribution to the development of anticancer drugs. PMID:27074628

  10. Synthesis of Phenoxazinone Derivatives and Antiproliferative Activities on Wild-type and Drug-resistant Tumor Cells

    Institute of Scientific and Technical Information of China (English)

    Ji Wu RUAN; Zhi Shu HUANG; Jin Feng HUANG; Cui Juan DU; Shi Liang HUANG; Zhi SHI; Li Wu FU; Lian Quan GU

    2006-01-01

    A series of novel phenoxazinone derivatives (1-6) were designed and synthesized for evaluating their antitumor activities. The antiproliferative activities of the prepared compounds against representative human neoplastic cell lines were evaluated by MTT assay. The results showed that most of them inhibited cell proliferation in a submicromolar to micromolar range.These compounds were also evaluated against KBv200 and MCF-7/Adr cell lines, which overexpress the MDR/P-glycoprotein drug efflux pump responsible for drug resistance, and had a more potential for resisting MDR than their lead compound APO.

  11. tert-Butylcarbamate-containing histone deacetylase inhibitors: apoptosis induction, cytodifferentiation, and antiproliferative activities in cancer cells.

    Science.gov (United States)

    Valente, Sergio; Trisciuoglio, Daniela; Tardugno, Maria; Benedetti, Rosaria; Labella, Donatella; Secci, Daniela; Mercurio, Ciro; Boggio, Roberto; Tomassi, Stefano; Di Maro, Salvatore; Novellino, Ettore; Altucci, Lucia; Del Bufalo, Donatella; Mai, Antonello; Cosconati, Sandro

    2013-05-01

    Herein we report novel pyrrole- and benzene-based hydroxamates (8, 10) and 2'-aminoanilides (9, 11) bearing the tert-butylcarbamate group at the CAP moiety as histone deacetylase (HDAC) inhibitors. Compounds 8 b and 10 c selectively inhibited HDAC6 at the nanomolar level, whereas the other hydroxamates effected an increase in acetyl-α-tubulin levels in human acute myeloid leukemia U937 cells. In the same cell line, compounds 8 b and 10 c elicited 18.4 and 21.4 % apoptosis, respectively (SAHA: 16.9 %), and the pyrrole anilide 9 c displayed the highest cytodifferentiating effect (90.9 %). In tests against a wide range of various cancer cell lines to determine its antiproliferative effects, compound 10 c exhibited growth inhibition from sub-micromolar (neuroblastoma LAN-5 and SH-SY5Y cells, chronic myeloid leukemia K562 cells) to low-micromolar (lung H1299 and A549, colon HCT116 and HT29 cancer cells) concentrations. In HT29 cells, 10 c increased histone H3 acetylation, and decreased the colony-forming potential of the cancer cells by up to 60 %. PMID:23526814

  12. Free radical scavenging property and antiproliferative activity of Rhodiola imbricata Edgew extracts in HT-29 human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ravichandran Senthilkumar; Thangaraj Parimelazhagan; Om Prakash Chaurasia; RB Srivastava

    2013-01-01

    Objective: To investigate the in vitro antioxidant and antiproliferative activity of rhizome extracts of Rhodiola imbricata (R. imbricata) in HT-29 human colon cancer cell line. Methods: The successively extracted rhizome of R. imbricata using various solvents was analyzed for their total phenolics, tannins and flavonoid contents. In vitro antioxidant activity was evaluated by employing different assays, including DPPH, ABTS radical scavenging assays, FRAP, phosphomolybdenum reduction assay, superoxide anion, hydroxyl radical scavenging activities and metal chelating ability. Results: Acetone and methanol extracts recorded higher phenolic content and showed comparable antioxidant activity with standard reference. Additionally, they also inhibited the proliferation of HT-29 cells upon treatment at higher concentration (200 μg/mL) (acetone and methanol, 84% and 84%, respectively). On examination acetone extract exhibited antiproliferative activity in a concentration dependent manner whereas, methanol extract showed both dose dependent and time dependent inhibitory activity. Conclusions: The results obtained justify the traditional usage of R. imbricata from their promising antioxidant activity.

  13. The Antiproliferative Effect of Moringa oleifera Crude Aqueous Leaf Extract on Human Esophageal Cancer Cells.

    Science.gov (United States)

    Tiloke, Charlette; Phulukdaree, Alisa; Chuturgoon, Anil A

    2016-04-01

    Esophageal cancer (EC) is commonly diagnosed in South Africa (SA), with high incidences occurring in SA's black population. Moringa oleifera (MO), a multipurpose tree, is used traditionally for its nutritional and medicinal properties. It has been used for the treatment of a variety of ailments, including cancer. We investigated the antiproliferative effect of MO crude aqueous leaf extract (MOE) on a cancerous esophageal cell line (SNO). SNO cells were exposed to a range of MOE dilutions to evaluate cytotoxicity (MTT assay). Oxidative stress was determined using the TBARS assay. The comet assay was used to assess DNA damage. We then determined cell death mechanisms by measuring phosphatidylserine (PS) externalization (flow cytometry), caspase-3/7 and caspase-9 activities, and adenosine triphosphate (ATP) levels (luminometry). Protein expression of Smac/DIABLO and PARP-1 was determined by western blotting. SNO cells were treated with a range of MOE dilutions to obtain an IC50 value of 389.2 μg/mL MOE (24 h), which was used in all subsequent assays. MOE significantly increased lipid peroxidation (P < .05) and DNA fragmentation (P < .0001) in SNO cells. The induction of apoptosis was confirmed by the increase in PS externalization (P < .0001), caspase-9 (P < .05) and caspase-3/7 (P = .22) activities, and decreased ATP levels (P < .0001). MOE significantly increased both the expression of Smac/DIABLO protein and cleavage of PARP-1, resulting in an increase in the 24-kDa fragment (P < .001). MOE possesses antiproliferative effects on SNO EC cells by increasing lipid peroxidation, DNA fragmentation, and induction of apoptosis. PMID:27074620

  14. Antiproliferative Activity of Cyanophora paradoxa Pigments in Melanoma, Breast and Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Laurent Picot

    2013-11-01

    Full Text Available The glaucophyte Cyanophora paradoxa (Cp was chemically investigated to identify pigments efficiently inhibiting malignant melanoma, mammary carcinoma and lung adenocarcinoma cells growth. Cp water and ethanol extracts significantly inhibited the growth of the three cancer cell lines in vitro, at 100 µg·mL−1. Flash chromatography of the Cp ethanol extract, devoid of c-phycocyanin and allophycocyanin, enabled the collection of eight fractions, four of which strongly inhibited cancer cells growth at 100 µg·mL−1. Particularly, two fractions inhibited more than 90% of the melanoma cells growth, one inducing apoptosis in the three cancer cells lines. The detailed analysis of Cp pigment composition resulted in the discrimination of 17 molecules, ten of which were unequivocally identified by high resolution mass spectrometry. Pheophorbide a, β-cryptoxanthin and zeaxanthin were the three main pigments or derivatives responsible for the strong cytotoxicity of Cp fractions in cancer cells. These data point to Cyanophora paradoxa as a new microalgal source to purify potent anticancer pigments, and demonstrate for the first time the strong antiproliferative activity of zeaxanthin and β-cryptoxanthin in melanoma cells.

  15. Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

    Directory of Open Access Journals (Sweden)

    Sarah Fernandes Teixeira

    2013-12-01

    Full Text Available OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity.METHODS: We used the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and calculated the combination index for the drugs studied.RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy.CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher.

  16. Antiproliferative effect of octreotide on gastric cancer cell smediated by inhibition of Akt/PKB and telomerase

    Institute of Scientific and Technical Information of China (English)

    Shan Gao; Bao-Ping Yu; Yan Li; Wei-Guo Dong; He-Sheng Luo

    2003-01-01

    AIM: To investigate the antiproliferative effect of octreotide,a long-acting analogue of somatostatin, on gastric cancer cell line SGC7901 and its possible molecular mechanisms.METHODS: Gastric cancer cell line SGC7901 employed in the study was treated with 0.008, 0.04, 0.2, 1, 5 and 25μg@ml-1 of octreotide respectively for 24 h to evaluate the antiproliferative effect of somatostatin analog on the tumor cells by MTT assay method. To elucidate the underlying mechanism, the cells were exposed to 1 μg@ml-1 of octreotide for 0, 12, 24 and 48 h, when their Akt/PKB and telomerase activities were respectively determined using PCR-ELSIA and nonradioactive protein kinase assay protocols. The same experimental procedures were also performed in the control cells that were treated with corresponding vehicles instead of somatostatin analog.RESULTS: After exposed to octreotide for 24 h at the concentrations of more than 1 μg@ml-1 SGC7901 cells exhibited a dose-dependent inhibition of growth with the inhibiting rate to be as high as 34.66 % when 25 μg@ml-1 of octreotide was applied. The Akt/PKB and telomerase activity of SGC7901 cells was significantly inhibited when the cells were exposed to 1 μg@ml-1 of octreotide for 12, 24 and 48 h compared with that of their control counterparts (P<0.01),both of which exhibited in a time-dependent manner.CONCLUSION: The antiproliferative effect of octreotide on SGC7901 cells might be mediated by the inhibition of Akt/PKB and telomerase.

  17. Synthesis and antiproliferative activity of new tonantzitlolone-derived diterpene derivatives.

    Science.gov (United States)

    Busch, Torsten; Dräger, Gerald; Kunst, Eike; Benson, Hannah; Sasse, Florenz; Siems, Karsten; Kirschning, Andreas

    2016-10-14

    The synthesis of the diterpene (+)-tonantzitlolone A and a series of derivatives is reported. The study includes the determination of their antiproliferative activities against selected cancer cell lines.

  18. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells

    OpenAIRE

    Pandiri, Indira; Chen, Yingqing; Joe, Yeonsoo; Kim, Hyo Jeong; Park, Jeongmin; Chung, Hun Taeg; Park, Jeong Woo

    2016-01-01

    Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantit...

  19. Antiproliferative activity of New Zealand propolis and phenolic compounds vs human colorectal adenocarcinoma cells.

    Science.gov (United States)

    Catchpole, Owen; Mitchell, Kevin; Bloor, Stephen; Davis, Paul; Suddes, Amanda

    2015-10-01

    New Zealand propolis is a "European" type propolis obtained by honey bees mainly from exudates of poplar. European type propolis is known to have anti-inflammatory and anti-cancer properties and this activity has been attributed to some of the main constituents such as chrysin and CAPE (caffeic acid phenethyl ester). As part of our studies on how New Zealand propolis might benefit gastro-intestinal health, we carried out in vitro bioactivity-guided fractionation of "Bio30™" propolis using both anti-inflammatory (TNF-α, COX-1, COX-2) and anti-colon cancer (DLD-1 colon cancer cell viability) assays; and determined the phenolic compounds responsible for the activity. The New Zealand wax-free Bio30™ propolis tincture solids had very high levels of the dihydroflavonoids pinocembrin and pinobanksin-3-O-acetate, and high levels of the dimethylallyl, benzyl and 3-methyl-3-butenyl caffeates relative to CAPE. The DLD-1 assays identified strong anti-proliferative activity associated with these components as well as chrysin, galangin and CAPE and a number of lesser known or lower concentration compounds including benzyl ferulate, benzyl isoferulate, pinostrobin, 5-phenylpenta-2,4-dienoic acid and tectochrysin. The phenolic compounds pinocembrin, pinobanksin-3-O-acetate, tectochrysin, dimethylallyl caffeate, 3-methyl-3-butenyl caffeate, benzyl ferulate and benzyl isoferulate also showed good broad spectrum activity in anti-proliferative assays against three other gastro-intestinal cancer cell lines; HCT-116 colon carcinoma, KYSE-30 oesophageal squamous cancer, and NCI-N87 gastric carcinoma. Activity is also observed in anti-inflammatory assays although it appears to be limited to one of the first cytokines in the inflammatory cascade, TNF-α. PMID:26347954

  20. Antiproliferative effect of immunoliposomes containing 5-fluorodeoxyuridine-dipalmitate on colon cancer cells

    NARCIS (Netherlands)

    Koning, GA; Gorter, A; Scherphof, GL; Kamps, JAAM

    1999-01-01

    We have investigated the antiproliferative action towards CC531 colon adenocarcinoma cells of target cell-specific immunoliposomes containing the amphiphilic dipalmitoyl derivative of 5-fluorodeoxyuridine (FUdR-dP). FUdR-dP incorporated in immunoliposomes caused a 13-fold stronger inhibition of CC53

  1. Antiproliferative and proapoptotic effects of viable or heat-killed Lactobacillus paracasei IMPC2.1 and Lactobacillus rhamnosus GG in HGC-27 gastric and DLD-1 colon cell lines.

    Science.gov (United States)

    Orlando, A; Refolo, M G; Messa, C; Amati, L; Lavermicocca, P; Guerra, V; Russo, F

    2012-01-01

    Data from literature suggest the possible use of probiotics as chemopreventive agents against colon cancer, but few investigations are available on their effects on gastric cancer proliferation. In our previous study, a specific Lactobacillus, strain L. paracasei IMPC2.1, was demonstrated to colonize the human gut and positively affect fecal bacteria and biochemical parameters. The aims of the present study were to investigate the effects of L. paracasei IMPC2.1, comparing them with those of Lactobacillus rhamnosus GG (L.GG), either as viable or heat-killed cells, on cell proliferation and apoptosis in a gastric cancer (HGC-27) and a colorectal cancer cell line (DLD-1). Both the gastric and colon cancer cells were sensitive to the growth inhibition and apoptosis induction by both viable or heat-killed cells from L. paracasei IMPC2.1 and L.GG. These findings suggest the possibility for a food supplement, based on dead probiotics, including L. paracasei IMPC2.1 cells, which could represent an effective component of a functional food strategy for cancer growth inhibition, with potential for cancer prevention. PMID:23061912

  2. trans-thionate derivatives of Pt(II) and Pd(II) with water-soluble phosphane PTA and DAPTA ligands: antiproliferative activity against human ovarian cancer cell lines.

    Science.gov (United States)

    Guerrero, Elena; Miranda, Susana; Lüttenberg, Sebastian; Fröhlich, Nils; Koenen, Jan-Moritz; Mohr, Fabian; Cerrada, Elena; Laguna, Mariano; Mendía, Aránzazu

    2013-06-01

    A series of PTA and DAPTA platinum(II) and palladium(II) thionate complexes of the type trans-[M(SN)2P2] were prepared from the reaction of cis-[MCl2P2] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)] with the in situ generated sodium salts of the heterocyclic thiones S-m-methylpyrimidine-2-thione, S-4,6-dimethylpyrimidine-2-thione, S-4,6-dihydroxypyrimidine-2-thione, benzothiazole-2-thione, benzoxazole-2-thione, S-1,3,4,-thiadiazole-2-thione, S-4,5-H-thiazolan-2-thione, and S-pyrimidine-4(1H)-one-2-thione. The X-ray structures of six of the compounds confirm the trans disposition and, only in the case of [Pd2Cl2(S-pyrimidine-4(1H)-one-2-thionate)2(PTA)2], a dinuclear structure with a Pd-Pd distance of 3.0265(14)Å was observed. In vitro cytotoxicities against human ovarian cancer cell lines A2780 and A2780cisR were evaluated for ten complexes showing a high inhibition of cellular growth with a comparable inhibitory potency (IC50) against A2780 cells to that of cisplatin. Notably, the compounds also show significant (up to 7-fold higher) activity in cisplatin-resistant A2780cisR cell lines. PMID:23692403

  3. Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells.

    Science.gov (United States)

    Pereira, Andreia; Bester, Megan; Soundy, Puffy; Apostolides, Zeno

    2016-09-01

    Context Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown that root extracts are rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. Objective This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). Materials and methods The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukaemia cell line at concentrations of 0-150 μg/mL. The effect on cell growth was determined with sulphorhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. The effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. Results Dihydroxycoumarin sulphates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL were observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 value of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 value of 9.7 μg/mL). The PST arrested Jurkat cells at the G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. Conclusion We present evidence that P. sidoides has cancer cell type-specific anti-proliferative effects and may be a source of novel anticancer molecules. PMID:26794080

  4. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Directory of Open Access Journals (Sweden)

    Lucia Cattaneo

    Full Text Available Rosemary (Rosmarinus officinalis L. has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed.

  5. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Science.gov (United States)

    Cattaneo, Lucia; Cicconi, Rosella; Mignogna, Giuseppina; Giorgi, Alessandra; Mattei, Maurizio; Graziani, Giulia; Ferracane, Rosalia; Grosso, Alessandro; Aducci, Patrizia; Schininà, M Eugenia; Marra, Mauro

    2015-01-01

    Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed. PMID:26176704

  6. In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Paula M. Kustiawan

    2014-07-01

    Conclusions: Propolis from T. incisa and Trigona fusco-balteata contain an in vitro cytotoxic activity against human cancer cell lines. Further study is required, including the isolation and characterization of the active antiproliferative agent(s.

  7. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells

    International Nuclear Information System (INIS)

    It is well established that obesity is a risk factor for breast cancer and that blood levels of adiponectin, a hormone mainly secreted by white adipocytes, are inversely correlated with the body fat mass. As adiponectin elicits anti-proliferative effects in some cell types, we tested the hypothesis that adiponectin could influence human breast cancer MCF-7 cell growth. Here we show that MCF-7 cells express adiponectin receptors and respond to human recombinant adiponectin by reducing their growth, AMPkinase activation, and p42/p44 MAPkinase inactivation. Further, we demonstrate that the anti-proliferative effect of adiponectin involves activation of cell apoptosis and inhibition of cell cycle. These findings suggest that adiponectin could act in vivo as a paracrine/endocrine growth inhibitor towards mammary epithelial cells. Moreover, adipose adiponectin production being strongly reduced in obesity, this study may help to explain why obesity is a risk factor of developing breast cancers

  8. Antiproliferative and Apoptotic Effects of a Specific Antiprostate Stem Cell Single Chain Antibody on Human Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Foroogh Nejatollahi

    2013-01-01

    Full Text Available Prostate stem cell antigen (PSCA is a highly glycosylated cell surface protein which is overexpressed in several malignancies including prostate, pancreas, and urinary bladder cancers. Tumor suppression has been reported by anti-PSCA antibody. Small and high affinity single chain antibodies (scFv have been introduced as effective agents for cancer immunotargeting approaches. In the present study, we used a phage antibody display library of scFv and selected two antibodies against two immunodominant epitopes of PSCA by panning process. The reactivity of the scFvs for the corresponding epitopes was determined by phage ELISA. The binding specificity of antibodies to PSCA-expressing prostate cancer cell line, DU-145, was analyzed by flow cytometry. The antiproliferative and apoptotic induction effects were evaluated by MTT and Annexin-V assays, respectively. Results represented functional scFv C5-II which could bind specifically to DU-145 cells and significantly inhibited the proliferation of these cells (61% with no effect on PSCA-negative cells. The antibody also induced apoptosis in the PSCA expressing cells. The percentage of the apoptotic cells after 24 hrs of exposure to 500 scFv/cell was 33.80%. These results demonstrate that the functional anti-PSCA scFv C5-II has the potential to be considered as a new agent for targeted therapy of prostate cancer.

  9. Antiproliferative effect of growth hormone-releasing hormone (GHRH antagonist on ovarian cancer cells through the EGFR-Akt pathway

    Directory of Open Access Journals (Sweden)

    Varga Jozsef

    2010-05-01

    Full Text Available Abstract Background Antagonists of growth hormone-releasing hormone (GHRH are being developed for the treatment of various human cancers. Methods MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR level and the phosphorylation of Akt (p-Akt, suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.

  10. Synthesis and antiproliferative activity of new bioconjugates of Salinomycin with amino acid esters.

    Science.gov (United States)

    Antoszczak, Michał; Sobusiak, Maria; Maj, Ewa; Wietrzyk, Joanna; Huczyński, Adam

    2015-09-01

    New Salinomycin (SAL) bioconjugates with amino acid methyl esters were obtained and their antiproliferative activity against cancer cell lines including drug-resistant ones was studied. New compounds exhibit antiproliferative activity towards leukemia and doxorubicin-resistant colon adenocarcinoma cell line and are more effective and less toxic than the commonly currently used anticancer drugs.

  11. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.

    Science.gov (United States)

    Pandiri, Indira; Chen, Yingqing; Joe, Yeonsoo; Kim, Hyo Jeong; Park, Jeongmin; Chung, Hun Taeg; Park, Jeong Woo

    2016-02-01

    Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against TTP to inhibit TTP expression or c-Myc and, after metformin treatment, analyzed for cell proliferation by MTS assay. Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin. We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation. Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin's anti-proliferative activity in cancer cells. PMID:26956973

  12. Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Frédéric Couture

    2015-01-01

    Full Text Available The overexpression as well as the critical implication of the proprotein convertase PACE4 in prostate cancer progression has been previously reported and supported the development of peptide inhibitors. The multi-Leu peptide, a PACE4-specific inhibitor, was further generated and its capability to be uptaken by tumor xenograft was demonstrated with regard to its PACE4 expression status. To investigate whether the uptake of this inhibitor was directly dependent of PACE4 levels, uptake and efflux from cancer cells were evaluated and correlations were established with PACE4 contents on both wild type and PACE4-knockdown cell lines. PACE4-knockdown associated growth deficiencies were established on the knockdown HepG2, Huh7, and HT1080 cells as well as the antiproliferative effects of the multi-Leu peptide supporting the growth capabilities of PACE4 in cancer cells.

  13. Antiproliferative effects on colon adenocarcinoma cells induced by co-administration of vitamin K1 and Lactobacillus rhamnosus GG.

    Science.gov (United States)

    Orlando, Antonella; Linsalata, Michele; Russo, Francesco

    2016-06-01

    Vitamin K (VK), an essential nutrient associated with the clotting cascade, has also been demonstrated to have anticancer properties in various cancer cells including colon cancer cells. Also probiotics have gained interest as potential anticancer agents. Among them, Lactobacillus rhamnosus GG (L.GG) has been shown to inhibit cell proliferation and polyamine biosynthesis as well as to induce apoptosis in different human gastrointestinal cancer cells. Nevertheless, the exact mechanisms involved in these actions are not completely elucidated. Therefore, the aims of the present study were to evaluate in three differently graded human colon cancer cells (namely Caco-2, HT-29 and SW480) the effects of increasing VK1 concentrations, administered alone or in combination with viable L.GG, on the cell proliferation evaluated by MTT test, apoptosis investigated by Bax/Bcl-2 ratio and the percentage of the apoptotic cells, and the cell cycle evaluated by MUSE cell analyzer. Both VK1 and L.GG administered alone up to 72 h, caused inhibition of proliferation, induction of apoptosis and the cell cycle arrest in all the tested colon cancer cells. When VK1 and L.GG were co-administered, the addition of increasing VK1 concentrations potentiated the probiotic antiproliferative effect in a dose-dependent manner, being also related to the individual features of each cell line. The effect was more evident in Caco-2 and HT-29 cells compared to the less differentiated SW480. The enhanced antiproliferative efficacy due to co-administration of L.GG and VK1 could represent a suitable option in a functional food strategy for cancer growth inhibition and chemoprevention. PMID:27035094

  14. Antiproliferative and apoptotic effects of butyrolactone lignans from Arctium lappa on leukemic cells.

    Science.gov (United States)

    Matsumoto, T; Hosono-Nishiyama, K; Yamada, H

    2006-02-01

    In the course of screening for pharmacologically active substances from extracts of crude drugs used traditionally in Sino-Japanese herbal medicines, it was found that the 70 % ethanol extract from the fruits of Arctium lappa L. (Compositae) showed potent antiproliferative activity against B cell hybridoma cell, MH60. By bioassay-guided purification, a new lignan, (+)-7,8-didehydroarctigenin, together with the known lignans (-)-arctigenin and (-)-matairesinol were isolated as the active ingredients from an aqueous ethanolic extract of the fruits of A. lappa. Of these active compounds, (-)-arctigenin showed the most potent antiproliferative activity against MH60 cells (IC (50) : 1.0 microM), and the activity was suggested to be due to apoptosis.

  15. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Angeliki Tiptiri-Kourpeti

    Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  16. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Science.gov (United States)

    Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

  17. Caffeic Acid Phenylethyl Ester and MG-132 Have Apoptotic and Antiproliferative Effects on Leukemic Cells But Not on Normal Mononuclear Cells12

    Science.gov (United States)

    Cavaliere, Victoria; Papademetrio, Daniela L; Lorenzetti, Mario; Valva, Pamela; Preciado, María Victoria; Gargallo, Patricia; Larripa, Irene; Monreal, Mariela B; Pardo, María Laura; Hajos, Silvia E; Blanco, Guillermo AC; Álvarez, Élida MC

    2009-01-01

    Chemotherapy aims to limit proliferation and induce apoptotic cell death in tumor cells. Owing to blockade of signaling pathways involved in cell survival and proliferation, nuclear factor κB (NF-κB) inhibitors can induce apoptosis in a number of hematological malignancies. The efficacy of conventional chemotherapeutic drugs, such as vincristine (VCR) and doxorubicine (DOX), may be enhanced with combined therapy based on NF-κB modulation. In this study, we evaluated the effect of caffeic acid phenylethyl ester (CAPE) and MG-132, two nonspecific NF-κB inhibitors, and conventional chemotherapeutics drugs DOX and VCR on cell proliferation and apoptosis induction on a lymphoblastoid B-cell line, PL104, established and characterized in our laboratory. CAPE and MG-132 treatment showed a strong antiproliferative effect accompanied by clear cell cycle deregulation and apoptosis induction. Doxorubicine and VCR showed antiproliferative effects similar to those of CAPE and MG-132, although the latter drugs showed an apoptotic rate two-fold higher than DOX and VCR. None of the four compounds showed cytotoxic effect on peripheral mononuclear cells from healthy volunteers. CAPE- and MG-132-treated bone marrow cells from patients with myeloid and lymphoid leukemias showed 69% (P < .001) and 25% decrease (P < .01) in cell proliferation and 42% and 34% (P < .01) apoptosis induction, respectively. Overall, our results indicate that CAPE and MG-132 had a strong and selective apoptotic effect on tumor cells that may be useful in future treatment of hematological neoplasias. PMID:19252751

  18. Synthesis and Antiproliferative Activities of 5-Azacytidine Analogues in Human Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Lin-Xiang Zhao

    2008-07-01

    Full Text Available Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl Snucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability as that of the latter. Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly decreased the antiproliferative activities of the 5-azacytidine derivatives. Several compounds with the replacement of pyranosyl sugars enhanced all-trans retinoic acid-induced differentiation ability in human leukemia HL-60 cells.

  19. Composite fiber structures with antiproliferative agents exhibit advantageous drug delivery and cell growth inhibition in vitro.

    Science.gov (United States)

    Kraitzer, Amir; Kloog, Yoel; Haklai, Roni; Zilberman, Meital

    2011-01-01

    Composite core/shell fiber structures loaded with the antiproliferative drugs paclitaxel or farnesylthiosalicylate (FTS) were developed and studied. The latter is a specific nontoxic Ras inhibitor with a mild hydrophobic nature, which can also be used for local cancer treatment and stent applications. The fibers were composed of a dense polyglyconate core and a porous drug-loaded poly(D,L-lactic-glycolic acid) shell, prepared using freeze drying of inverted emulsions. Our study focused on the release profile of the antiproliferative drugs from the fibers, the shell morphology and its degradation and erosion. The postfabrication antiproliferative effect of the drugs was tested in a cell culture. The process parameters were found to affect the drug-release profile via two routes: (1) direct, through water uptake and swelling of the structure leading to FTS release, or through degradation of the host polymer leading to paclitaxel release at a later stage; (2) indirect effect of the microstructure on the release profile. The fabrication process did not reduce the pharmacological activity of either paclitaxel or FTS. FTS-eluting composite fibers proved to effectively induce growth inhibition or cell death by a gradient effect and dose-dependent manner. The combined effect of the targeted mechanism of FTS as a Ras inhibitor together with the localized and controlled release characteristics of the fiber is an advantageous antiproliferative quality. It is therefore suggested that our drug-eluting fibers may be used in biomedical applications that require short release (restenosis) or prolonged release (cancer therapy). PMID:20623695

  20. Differences in antiproliferative effect of STAT3 inhibition in HCC cells with versus without HBV expression

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Yun; Zhou, Lin; Xie, Haiyang; Wang, Weilin [Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Zheng, Shusen, E-mail: shusenzheng@zju.edu.cn [Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China)

    2015-06-05

    Chronic infection with hepatitis B virus (HBV) plays an important role in the etiology of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3) inactivation could inhibit the tumor growth of HCC. In this study, differential antiproliferative effect of STAT3 inhibition was observed with HBV-related HCC cells being more resistant than non-HBV-related HCC cells. Resistance of HBV-related HCC cells to STAT3 inhibition was positively correlated to the expression of HBV. Enhanced ERK activation after STAT3 blockade was detected in HBV-related HCC cells but not in non-HBV-related HCC cells. Combined ERK and STAT3 inhibition eliminates the discrepancy between the two types of HCC cells. Moderate reduced HBV expression was found after STAT3 inhibition. These findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells. - Highlights: • HBV endows HCC cells with resistance to STAT3 inactivation on proliferation. • Abnormal ERK activation after STAT3 inhibition in HBV-related HCC cells. • Combined ERK and STAT3 inhibition eliminates the discrepancy. • STAT3 inhibition moderately reduces HBV expression.

  1. High Performance Liquid Chromatography-mass Spectrometry Analysis of High Antioxidant Australian Fruits with Antiproliferative Activity Against Cancer Cells

    Science.gov (United States)

    Sirdaarta, Joseph; Maen, Anton; Rayan, Paran; Matthews, Ben; Cock, Ian Edwin

    2016-01-01

    Background: High antioxidant capacities have been linked to the treatment and prevention of several cancers. Recent reports have identified several native Australian fruits with high antioxidant capacities. Despite this, several of these species are yet to be tested for anticancer activity. Materials and Methods: Solvent extracts prepared from high antioxidant native Australian fruits were analyzed for antioxidant capacity by the di (phenyl)-(2,4,6-trinitrophenyl) iminoazanium free radical scavenging assay. Antiproliferative activities against CaCo2 and HeLa cancer cells were determined by a multicellular tumor spheroid-based cell proliferation assay. Toxicity was determined by Artemia franciscana bioassay. Results: Methanolic extracts of all plant species displayed high antioxidant contents (equivalent to approximately 7–16 mg of vitamin C per gram of fruit extracted). Most aqueous extracts also contained relatively high antioxidant capacities. In contrast, the ethyl acetate, chloroform, and hexane extracts of most species (except lemon aspen and bush tomato) had lower antioxidant contents (below 1.5 mg of vitamin C equivalents per gram of plant material extracted). The antioxidant contents correlated with the ability of the extracts to inhibit proliferation of CaCo2 and HeLa cancer cell lines. The high antioxidant methanolic extracts of all species were potent inhibitors of cell proliferation. The methanolic lemon aspen extract was particularly effective, with IC50 values of 480 and 769 μg/mL against HeLa and CaCo2 cells, respectively. In contrast, the lower antioxidant ethyl acetate and hexane extracts (except the lemon aspen ethyl acetate extract) generally did not inhibit cancer cell proliferation or inhibited to only a minor degree. Indeed, most of the ethyl acetate and hexane extracts induced potent cell proliferation. The native tamarind ethyl acetate extract displayed low-moderate toxicity in the A. franciscana bioassay (LC50 values below 1000

  2. Cinnamomum verum component 2-methoxycinnamaldehyde: a novel antiproliferative drug inducing cell death through targeting both topoisomerase I and II in human colorectal adenocarcinoma COLO 205 cells

    Science.gov (United States)

    Tsai, Kuen-daw; Cherng, Jonathan; Liu, Yi-Heng; Chen, Ta-Wei; Wong, Ho-Yiu; Yang, Shu-mei; Chou, Kuo-Shen; Cherng, Jaw-Ming

    2016-01-01

    Background Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. Methods We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VACs) were determined by neutral red staining. Results The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm) loss, activation of both caspase-3 and -9, increase of annexin V+PI+ cells, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2-MCA found in a nude mice model. Conclusions Our data implicate that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor burden that could have significant clinical impact. Indeed, similar effects were found in other tested cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown). Our data implicate that 2-MCA could be a

  3. Induction of antiproliferative effect by diosgenin through activation of p53,release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells

    Institute of Scientific and Technical Information of China (English)

    Cecile CORBIERE; Bertrand LIAGRE; Faraj TERRO; Jean-Louis BENEYTOUT

    2004-01-01

    Previously, we demonstrated that a plant steroid, diosgenin, altered cell cycle distribution and induced apoptosis in the human osteosarcoma 1547 cell line. The objective of this study was to investigate if the antiproliferative effect of diosgenin was similar for different human cancer cell lines such as laryngocarcinoma HEp-2 and melanoma M4Beu cells. Moreover, this work essentially focused on the mitochondrial pathway. We found that diosgenin had an important and similar antiproliferative effect on different types of cancer cells. In addition, our new results show that diosgenininduced apoptosis is caspase-3 dependent with a fall of mitochondrial membrane potential, nuclear localization of AIF and poly (ADP-ribose) polymerase cleavage. Diosgenin treatment also induces p53 activation and cell cycle arrest in the different cell lines studied.

  4. Tocopherols and saponins derived from Argania spinosa exert, an antiproliferative effect on human prostate cancer.

    Science.gov (United States)

    Drissi, A; Bennani, H; Giton, F; Charrouf, Z; Fiet, J; Adlouni, A

    2006-10-01

    The aim of our study is to evaluate the antiproliferative effect of tocopherols obtained from alimentary virgin argan oil extracted from the endemic argan tree of Morocco and of saponins extracted from argan press cake on three human prostatic cell lines (DU145, LNCaP, and PC3). The results were compared to 2-methoxyestradiol as antiproliferative drug candidates. Cytotoxicity and antiproliferative effects were investigated after cells' treatment with tocopherols and saponins compared to 2-Methoxyoestradiol as the positive control. Tocopherols and saponins extracted from argan tree and 2-methoxyestradiol exhibit a dose-response cytotoxic effect and an antiproliferative action on the tested cell lines. The best antiproliferative effect of tocopherols is obtained with DU145 and LNCaP cell lines (28 microg/ml and 32 microg/ml, respectively, as GI50). The saponins fraction displayed the best antiproliferative effect on the PC3 cell line with 18 microg/ml as GI50. Our results confirm the antiproliferative effect of 2-methoxyestradiol and show for the first time the antiproliferative effect of tocopherols and saponins extracted from the argan tree on hormone-dependent and hormone-independent prostate cancer cell lines. These data suggest that argan oil is of potential interest in developing new strategies for prostate cancer prevention.

  5. Tocopherols and saponins derived from Argania spinosa exert, an antiproliferative effect on human prostate cancer.

    Science.gov (United States)

    Drissi, A; Bennani, H; Giton, F; Charrouf, Z; Fiet, J; Adlouni, A

    2006-10-01

    The aim of our study is to evaluate the antiproliferative effect of tocopherols obtained from alimentary virgin argan oil extracted from the endemic argan tree of Morocco and of saponins extracted from argan press cake on three human prostatic cell lines (DU145, LNCaP, and PC3). The results were compared to 2-methoxyestradiol as antiproliferative drug candidates. Cytotoxicity and antiproliferative effects were investigated after cells' treatment with tocopherols and saponins compared to 2-Methoxyoestradiol as the positive control. Tocopherols and saponins extracted from argan tree and 2-methoxyestradiol exhibit a dose-response cytotoxic effect and an antiproliferative action on the tested cell lines. The best antiproliferative effect of tocopherols is obtained with DU145 and LNCaP cell lines (28 microg/ml and 32 microg/ml, respectively, as GI50). The saponins fraction displayed the best antiproliferative effect on the PC3 cell line with 18 microg/ml as GI50. Our results confirm the antiproliferative effect of 2-methoxyestradiol and show for the first time the antiproliferative effect of tocopherols and saponins extracted from the argan tree on hormone-dependent and hormone-independent prostate cancer cell lines. These data suggest that argan oil is of potential interest in developing new strategies for prostate cancer prevention. PMID:16982463

  6. Novel "hybrid" iron chelators derived from aroylhydrazones and thiosemicarbazones demonstrate selective antiproliferative activity against tumor cells.

    Science.gov (United States)

    Lovejoy, David B; Richardson, Des R

    2002-07-15

    We previously demonstrated that 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) and other aroylhydrazone chelators possess potent antineoplastic activity because of their ability to bind iron (Fe). From these studies, we identified structural components of the hydrazones that provide antineoplastic activity, namely the salicylaldehyde and 2-hydroxy-1-naphthylaldehyde moieties. A related group of chelators known as the thiosemicarbazones also show pronounced antitumor activity because of their ability to inhibit ribonucleotide reductase. Considering this, we designed a new series of "hybrid ligands" by condensation of the aldehydes described above with a range of thiosemicarbazides. The parent compound of these ligands is 2-hydroxy-1-naphthylaldehyde thiosemicarbazone (NT). Of 8 NT analogues, 3 chelators, namely NT, N4mT (2-hydroxy-1-naphthylaldehyde-4-methyl-3-thiosemicarbazone), and N44mT (2-hydroxy-1-naphthylaldehyde-4,4-dimethyl-3-thiosemicarbazone), showed high antiproliferative activity against SK-N-MC neuroepithelioma cells (50% inhibitory concentration [IC(50)] = 0.5-1.5 microM). Indeed, their activity was significantly (P <.0001) greater than that of desferrioxamine (DFO) (IC(50) = 22 microM). We demonstrate that 311, a 311 analogue (311m), and several NT-series chelators have significantly (P <.001) greater antiproliferative activity against tumor cells than against a range of normal cell types. For example, the IC(50) values of NT and N4mT in SK-N-MC neuroepithelioma cells were 0.5 microM, whereas for fibroblasts the IC(50) values were greater than 25 microM. Further, the effect of one of the most potent chelators (311m) on preventing the growth of bone marrow stem cell cultures was far less than that of doxorubicin and similar to that of cisplatin. These studies support the further development of these chelators as antiproliferative agents. PMID:12091363

  7. Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells.

    Directory of Open Access Journals (Sweden)

    Elisa Robles-Escajeda

    Full Text Available Green barley extract (GB was investigated for possible anti-cancer activity by examining its anti-proliferative and pro-apoptotic properties on human leukemia/lymphoma cell lines. Our results indicate that GB exhibits selective anti-proliferative activity on a panel of leukemia/lymphoma cells in comparison to non-cancerous cells. Specifically, GB disrupted the cell-cycle progression within BJAB cells, as manifested by G2/M phase arrest and DNA fragmentation, and induced apoptosis, as evidenced by phosphatidylserine (PS translocation to the outer cytoplasmic membrane in two B-lineage leukemia/lymphoma cell lines. The pro-apoptotic effect of GB was found to be independent of mitochondrial depolarization, thus implicating extrinsic cell death pathways to exert its cytotoxicity. Indeed, GB elicited an increase of TNF-α production, caspase-8 and caspase-3 activation, and PARP-1 cleavage within pre-B acute lymphoblastic leukemia Nalm-6 cells. Moreover, caspase-8 and caspase-3 activation and PARP-1 cleavage were strongly inhibited/blocked by the addition of the specific caspase inhibitors Z-VAD-FMK and Ac-DEVD-CHO. Furthermore, intracellular signaling analyses determined that GB treatment enhanced constitutive activation of Lck and Src tyrosine kinases in Nalm-6 cells. Taken together, these findings indicate that GB induced preferential anti-proliferative and pro-apoptotic signals within B-lineage leukemia/lymphoma cells, as determined by the following biochemical hallmarks of apoptosis: PS externalization, enhanced release of TNF-α, caspase-8 and caspase-3 activation, PARP-1 cleavage and DNA fragmentation Our observations reveal that GB has potential as an anti-leukemia/lymphoma agent alone or in combination with standard cancer therapies and thus warrants further evaluation in vivo to support these findings.

  8. Anti-proliferative activity of Monensin and its tertiary amide derivatives.

    Science.gov (United States)

    Huczyński, Adam; Klejborowska, Greta; Antoszczak, Michał; Maj, Ewa; Wietrzyk, Joanna

    2015-10-15

    New tertiary amide derivatives of polyether ionophore Monensin A (MON) were synthesised and their anti-proliferative activity against cancer cell lines was studied. Very high activity (IC50=0.09 μM) and selectivity (SI=232) of MON against human biphenotypic myelomonocytic leukemia cell line (MV4-11) was demonstrated. The MON derivatives obtained exhibit interesting anti-proliferative activity, high selectivity index and also are able to break the drug-resistance of cancer cell line.

  9. Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Viola Baradari; Michael H(o)pfner; Alexander Huether; Detlef Schuppan; Hans Scherübl

    2007-01-01

    AIM: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin)or the novel anticancer agents sorafenib or bortezomib.METHODS: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes.Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase (LDH).Apoptosis was determined by measuring the enzyme activity of caspase-3. Cell cycle status reflected by the DNA content was detected by flow cytometry.RESULTS: MS-275 treatment potently inhibited the proliferation of EGI-1 and TFK-1 cholangiocarcinoma cells by inducing apoptosis and cell cycle arrest. MS-275-induced apoptosis was characterized by activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. Cell cycle was predominantly arrested at the G1/S checkpoint, which was associated with induction of the cyclin-dependent kinase inhibitor p21Waf/CIP1. Furthermore,additive anti-neoplastic effects were observed when MS-275 treatment was combined with gemcitabine or doxorubicin, while combination with the multikinase inhibitor sorafenib or the proteasome inhibitor bortezomib resulted in overadditive anti-neoplastic effects.CONCLUSION: The growth of human cholangiocarcinoma cells can be potently inhibited by MS-275 alone or in combination with conventional cytostatic drugs or new,targeted anticancer agents.

  10. Cytotoxic Activity and Antiproliferative Effects of Crude Skin Secretion from Physalaemus nattereri (Anura: Leptodactylidae on in vitro Melanoma Cells

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    Andréa Cruz e Carvalho

    2015-10-01

    Full Text Available Anuran secretions are rich sources of bioactive molecules, including antimicrobial and antitumoral compounds. The aims of this study were to investigate the therapeutic potential of Physalaemus nattereri skin secretion against skin cancer cells, and to assess its cytotoxic action mechanisms on the murine melanoma cell line B16F10. Our results demonstrated that the crude secretion reduced the viability of B16F10 cells, causing changes in cell morphology (e.g., round shape and structure shrinkage, reduction in mitochondrial membrane potential, increase in phosphatidylserine exposure, and cell cycle arrest in S-phase. Together, these changes suggest that tumor cells die by apoptosis. This skin secretion was also subjected to chromatographic fractioning using RP-HPLC, and eluted fractions were assayed for antiproliferative and antibacterial activities. Three active fractions showed molecular mass components in a range compatible with peptides. Although the specific mechanisms causing the reduced cell viability and cytotoxicity after the treatment with crude secretion are still unknown, it may be considered that molecules, such as the peptides found in the secretion, are effective against B16F10 tumor cells. Considering the growing need for new anticancer drugs, data presented in this study strongly reinforce the validity of P. nattereri crude secretion as a rich source of new anticancer molecules.

  11. A bioguided identification of the active compounds that contribute to the antiproliferative/cytotoxic effects of rosemary extract on colon cancer cells.

    Science.gov (United States)

    Borrás-Linares, Isabel; Pérez-Sánchez, Almudena; Lozano-Sánchez, Jesús; Barrajón-Catalán, Enrique; Arráez-Román, David; Cifuentes, Alejandro; Micol, Vicente; Carretero, Antonio Segura

    2015-06-01

    Rosemary extracts have exhibited potential cytostatic or cytotoxic effects in several cancer cell models but their bioactive compounds are yet to be discovered. In this work, the anticancer activity of a rosemary-leaf extract and its fractions were assayed to identify the phenolic compounds responsible for their antiproliferative/cytotoxic effects on a panel of human colon cancer cell lines. Bioguided fractionation of the rosemary-leaf extract was achieved by semi-preparative chromatography. The rosemary extract and the compounds in the fractions were characterized and quantified by HPLC-ESI-QTOF-MS. Cellular viability in the presence of these fractions and the whole extract was determined after 24 or 48 h incubations by using an MTT assay. Fractions containing diterpenes or triterpenes were the most active but not as much as the whole extract. In conclusion, carnosic acid, carnosol, 12-methoxycarnosic acid, taxodione, hinokione and betulinic acid were the putative candidates that contributed to the observed antiproliferative activity of rosemary in human colon cancer cells. Whether the effects of the extract and fractions are only cytostatic or cytotoxic needs to be elucidated. Nevertheless, the comparative antiproliferative study on the fractions and whole extract revealed potential synergistic effects between several components in the extract that may deserve further attention. PMID:25801906

  12. Antiproliferative effects of fluoxetine on colon cancer cells and in a colonic carcinogen mouse model.

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    Vinicius Kannen

    Full Text Available The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG as models. Fluoxetine increased the percentage of HT29 cells in the G(0/G(1 phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.

  13. Antiproliferative activity of melanoidins isolated from heated potato fiber (potex) in glioma cell culture model.

    Science.gov (United States)

    Langner, Ewa; Nunes, Fernando M; Pozarowski, Piotr; Kandefer-Szerszeń, Martyna; Pierzynowski, Stefan G; Rzeski, Wojciech

    2011-03-23

    Potex constitutes a potato fiber preparation widely used as an ingredient to meat and bakery products which thermal treatment results in creation of new compounds. Melanoidins are high molecular weight brown end products of Maillard reaction, and few data presenting tumor cell growth inhibiting activity of melanoidins have been reported. Thus, in present study we utilized water extract of Potex roasted (180 °C for 2 h), whose chemical characterization revealed the presence of melanoidin complexes. Heated Potex extract inhibited C6 glioma cell proliferation in a dose-dependent manner measured by MTT method. High molecular weight components present in initial extract were responsible for stronger antiproliferative effect compared with low molecular weight fraction. Impaired MAPK (mitogen-activated protein kinase) and Akt signaling was found in cells treated with the extract. Moreover, flow cytometry analyses revealed the extract to induce G1/S arrest in glioma cells. Simultaneously, Western blot analysis showed elevated levels of p21 protein with concomitant decrease of cyclin D1. In conclusion, observed antiproliferative activity of melanoidins present in heated Potex was linked to disregulated MAPK and Akt signaling pathways, as well as to cell cycle cessation. These results suggest potential application of Potex preparation as a functional food ingredient and chemopreventive agent.

  14. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

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    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  15. Verapamil stereoisomers induce antiproliferative effects in vascular smooth muscle cells via autophagy

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    Salabei, Joshua K. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202 (United States); Balakumaran, Arun [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Frey, Justin C. [Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54702 (United States); Boor, Paul J. [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Treinen-Moslen, Mary [Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555‐0609 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Division of Cardiovascular Medicine, University of Louisville, Louisville, KY 40202 (United States); Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54702 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States)

    2012-08-01

    Calcium channel blockers (CCBs) are important in the management of hypertension and limit restenosis. Although CCB efficacy could derive from decreased blood pressure, other mechanisms independent of CCB activity also can contribute to antiproliferative action. To understand mechanisms of CCB-mediated antiproliferation, we studied two structurally dissimilar CCBs, diltiazem and verapamil, in cultured rat vascular smooth muscle cells (VSMC). To elucidate CCB-independent effects, pure stereoisomers of verapamil (R-verapamil, inactive VR; S-verapamil, active, VS) were used. The effects of CCB exposure on cell viability (MTT reduction), cell proliferation ({sup 3}H-thymidine incorporation), VSMC morphology by light and transmission electron microscopy (TEM) and autophagy (LC3I/II, ATG5) were measured. In general, verapamil, VR or VS treatment alone (80 μM) appreciably enhanced MTT absorbance although higher concentrations (VR or VS) slightly decreased MTT absorbance. Diltiazem (140 μM) markedly decreased MTT absorbance (40%) at 120 h. VR or VS treatment inhibited {sup 3}H-thymidine incorporation (24 h) and induced cytological alterations (i.e., karyokinesis, enhanced perinuclear MTT deposition, accumulated perinuclear “vacuoles”). TEM revealed perinuclear “vacuoles” to be aggregates of highly laminated and electron-dense vesicles resembling autophagosomes and lysosomes, respectively. Increased autophagosome activity was confirmed by a concentration-dependent increase in LC3-II formation by Western blotting and by increased perinuclear LC3-GFP{sup +} puncta in verapamil-treated VSMC. Verapamil stereoisomers appeared to decrease perinuclear mitochondrial density. These observations indicate that antiproliferative effects of verapamil stereoisomers are produced by enhanced mitochondrial damage and upregulated autophagy in VSMC. These effects are independent of CCB activity indicating a distinct mechanism of action that could be targeted for more efficacious anti

  16. Synthesis and Antiproliferative Activities of 5-Azacytidine Analogues in Human Leukemia Cells

    OpenAIRE

    Lin-Xiang Zhao; Yong-Kui Jing; Yu Liu; Qian-Jiao Yang; Dan Liu; Gang Li; Gang Guo

    2008-01-01

    Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl Snucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproli...

  17. Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells.

    Science.gov (United States)

    Pilarski, Radosław; Poczekaj-Kostrzewska, Magdalena; Ciesiołka, Danuta; Szyfter, Krzysztof; Gulewicz, Krzysztof

    2007-01-01

    The woody Amazonian vine Uncaria tomentosa (cat's claw) has been recently more and more popular all over the world as an immunomodulatory, antiinflammatory and anti-cancer remedy. This study investigates anti-proliferative potency of several cat's claw preparations with different quantitative and qualitative alkaloid contents on HL-60 acute promyelocytic human cells by applying trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay (MTT). By standardization and statistical comparison of the obtained results pteropodine and isomitraphylline are indicated to be most suitable for standardization of medical cat's claw preparations.

  18. Xanthones from Garcinia paucinervis with in vitro anti-proliferative activity against HL-60 cells.

    Science.gov (United States)

    Li, Da-Hong; Li, Chen-Xi; Jia, Cui-Cui; Sun, Ya-Ting; Xue, Chun-Mei; Bai, Jiao; Hua, Hui-Ming; Liu, Xiao-Qiu; Li, Zhan-Lin

    2016-02-01

    Three new xanthones, paucinervins H-J (1-3), as well as eleven known compounds (4-14), were isolated from the leaves of Garcinia paucinervis. The structures of the new compounds (1-3) were elucidated by 1D, 2D NMR spectra and HR ESIMS. In vitro antiproliferative activity against human promyelocytic leukemia HL-60 cells was tested, among which, compounds 2, 5, 6 and 7 exhibited strong growth inhibitory effects with GI50 values ranging from 1.30 to 9.08 μM, respectively. Preliminary SARs were also discussed. PMID:26659874

  19. Potent antiproliferative cembrenoids accumulate in tobacco upon infection with Rhodococcus fascians and trigger unusual microtubule dynamics in human glioblastoma cells.

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    Aminata P Nacoulma

    Full Text Available AIMS: Though plant metabolic changes are known to occur during interactions with bacteria, these were rarely challenged for pharmacologically active compounds suitable for further drug development. Here, the occurrence of specific chemicals with antiproliferative activity against human cancer cell lines was evidenced in hyperplasia (leafy galls induced when plants interact with particular phytopathogens, such as the Actinomycete Rhodococcus fascians. METHODS: We examined leafy galls fraction F3.1.1 on cell proliferation, cell division and cytoskeletal disorganization of human cancer cell lines using time-lapse videomicroscopy imaging, combined with flow cytometry and immunofluorescence analysis. We determined the F3.1.1-fraction composition by gas chromatography coupled to mass spectrometry. RESULTS: The leafy galls induced on tobacco by R. fascians yielded fraction F3.1.1 which inhibited proliferation of glioblastoma U373 cells with an IC50 of 4.5 µg/mL, F.3.1.1 was shown to increase cell division duration, cause nuclear morphological deformations and cell enlargement, and, at higher concentrations, karyokinesis defects leading to polyploidization and apoptosis. F3.1.1 consisted of a mixture of isomers belonging to the cembrenoids. The cellular defects induced by F3.1.1 were caused by a peculiar cytoskeletal disorganization, with the occurrence of fragmented tubulin and strongly organized microtubule aggregates within the same cell. Colchicine, paclitaxel, and cembrene also affected U373 cell proliferation and karyokinesis, but the induced microtubule rearrangement was very different from that provoked by F3.1.1. Altogether our data indicate that the cembrenoid isomers in F3.1.1 have a unique mode of action and are able to simultaneously modulate microtubule polymerization and stability.

  20. Dimeric Labdane Diterpenes: Synthesis and Antiproliferative Effects

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    Guillermo Schmeda-Hirschmann

    2013-05-01

    Full Text Available Several diterpenes with the labdane skeleton show biological activity, including antiproliferative effects. Most of the research work on bioactive labdanes has been carried out on naturally occurring diterpenes and semisynthetic derivatives, but much less is known on the effects of diterpene dimers. The aim of the present work was to synthesize dimeric diterpenes from the labdane imbricatolic acid using esters, ethers and the triazole ring as linkers. Some 18 new derivatives were prepared and the compounds were evaluated for antiproliferative activity on human normal fibroblasts (MRC-5 and the following human tumor cell lines: AGS, SK-MES-1, J82 and HL-60. The diethers 8–10, differing in the number of CH2 units in the linker, presented better antiproliferative activity with a maximum effect for the derivative 9. The best antiproliferative effect against HL-60 cells was found for compounds 3 and 17, with IC50 values of 22.3 and 23.2 μM, lower than that found for the reference compound etoposide (2.23 μM. The compounds 9, 17 and 11 were the most active derivatives towards AGS cells with IC50 values of 17.8, 23.4 and 26.1 μM. A free carboxylic acid function seems relevant for the effect as several of the compounds showed less antiproliferative effect after methylation.

  1. A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells.

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    Elena Bausch

    Full Text Available Microtubule inhibitors are invaluable tools in cancer chemotherapy: taxanes and vinca alkaloids have been successfully used in the clinic over the past thirty years against a broad range of tumors. However, two factors have limited the effectiveness of microtubule inhibitors: toxicity and resistance. In particular, the latter is highly unpredictable, variable from patient to patient and is believed to be the cause of treatment failure in most cases of metastatic cancers. For these reasons, there is an increasing demand for new microtubule inhibitors that can overcome resistance mechanisms and that, at the same time, have reduced side effects. Here we present a novel microtubule inhibitor, 4SC-207, which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay/arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. In summary, our results suggest that 4SC-207 may be a potential anti-cancer agent.

  2. Antiproliferative and Molecular Mechanism of Eugenol-Induced Apoptosis in Cancer Cells

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    Eko Supriyanto

    2012-05-01

    Full Text Available Phenolic phytochemicals are a broad class of nutraceuticals found in plants which have been extensively researched by scientists for their health-promoting potential. One such a compound which has been comprehensively used is eugenol (4-allyl-2-methoxyphenol, which is the active component of Syzigium aromaticum (cloves. Aromatic plants like nutmeg, basil, cinnamon and bay leaves also contain eugenol. Eugenol has a wide range of applications like perfumeries, flavorings, essential oils and in medicine as a local antiseptic and anesthetic. Increasing volumes of literature showed eugenol possesses antioxidant, antimutagenic, antigenotoxic, anti-inflammatory and anticancer properties. Molecular mechanism of eugenol-induced apoptosis in melanoma, skin tumors, osteosarcoma, leukemia, gastric and mast cells has been well documented. This review article will highlight the antiproliferative activity and molecular mechanism of the eugenol induced apoptosis against the cancer cells and animal models.

  3. Antiproliferative and molecular mechanism of eugenol-induced apoptosis in cancer cells.

    Science.gov (United States)

    Jaganathan, Saravana Kumar; Supriyanto, Eko

    2012-01-01

    Phenolic phytochemicals are a broad class of nutraceuticals found in plants which have been extensively researched by scientists for their health-promoting potential. One such a compound which has been comprehensively used is eugenol (4-allyl-2-methoxyphenol), which is the active component of Syzigium aromaticum (cloves). Aromatic plants like nutmeg, basil, cinnamon and bay leaves also contain eugenol. Eugenol has a wide range of applications like perfumeries, flavorings, essential oils and in medicine as a local antiseptic and anesthetic. Increasing volumes of literature showed eugenol possesses antioxidant, antimutagenic, antigenotoxic, anti-inflammatory and anticancer properties. Molecular mechanism of eugenol-induced apoptosis in melanoma, skin tumors, osteosarcoma, leukemia, gastric and mast cells has been well documented. This review article will highlight the antiproliferative activity and molecular mechanism of the eugenol induced apoptosis against the cancer cells and animal models. PMID:22634840

  4. Cooperative antiproliferative signaling by aspirin and indole-3-carbinol targets microphthalmia-associated transcription factor gene expression and promoter activity in human melanoma cells.

    Science.gov (United States)

    Poindexter, Kevin M; Matthew, Susanne; Aronchik, Ida; Firestone, Gary L

    2016-04-01

    Antiproliferative signaling of combinations of the nonsteroidal anti-inflammatory drug acetylsalicylic acid (aspirin) and indole-3-carbinol (I3C), a natural indolecarbinol compound derived from cruciferous vegetables, was investigated in human melanoma cells. Melanoma cell lines with distinct mutational profiles were sensitive to different extents to the antiproliferative response of aspirin, with oncogenic BRAF-expressing G361 cells and wild-type BRAF-expressing SK-MEL-30 cells being the most responsive. I3C triggered a strong proliferative arrest of G361 melanoma cells and caused only a modest decrease in the proliferation of SK-MEL-30 cells. In both cell lines, combinations of aspirin and I3C cooperatively arrested cell proliferation and induced a G1 cell cycle arrest, and nearly ablated protein and transcript levels of the melanocyte master regulator microphthalmia-associated transcription factor isoform M (MITF-M). In melanoma cells transfected with a -333/+120-bp MITF-M promoter-luciferase reporter plasmid, treatment with aspirin and I3C cooperatively disrupted MITF-M promoter activity, which accounted for the loss of MITF-M gene products. Mutational analysis revealed that the aspirin required the LEF1 binding site, whereas I3C required the BRN2 binding site to mediate their combined and individual effects on MITF-M promoter activity. Consistent with LEF1 being a downstream effector of Wnt signaling, aspirin, but not I3C, downregulated protein levels of the Wnt co-receptor LDL receptor-related protein-6 and β-catenin and upregulated the β-catenin destruction complex component Axin. Taken together, our results demonstrate that aspirin-regulated Wnt signaling and I3C-targeted signaling pathways converge at distinct DNA elements in the MITF-M promoter to cooperatively disrupt MITF-M expression and melanoma cell proliferation. PMID:27055402

  5. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

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    Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming, E-mail: erc1080@gmail.com; Wang, Yujiong, E-mail: erc1080@gmail.com [Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Yinchuan 750021, Ningxia (China); College of Life Science, Ningxia University, Yinchuan 750021, Ningxia (China)

    2012-12-04

    In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC{sub 50}) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC{sub 50} values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs.

  6. Antiproliferative and pro-apoptotic effects of Uncaria tomentosa in human medullary thyroid carcinoma cells.

    Science.gov (United States)

    Rinner, Beate; Li, Zeng Xia; Haas, Helga; Siegl, Veronika; Sturm, Sonja; Stuppner, Hermann; Pfragner, Roswitha

    2009-11-01

    Medullary thyroid carcinoma (MTC), a rare calcitonin-producing tumor, is derived from parafollicular C-cells of the thyroid and is characterized by constitutive Bcl-2 overexpression. The tumor is relatively insensitive to radiation therapy as well as conventional chemotherapy. To date, the only curative treatment is the early and complete surgical removal of all neoplastic tissue. In this study, the antiproliferative and pro-apoptotic effects of fractions obtained from Uncaria tomentosa (Willd.) DC, commonly known as uña de gato or cat's claw were investigated. Cell growth of MTC cells as well as enzymatic activity of mitochondrial dehydrogenase was markedly inhibited after treatment with different fractions of the plant. Furthermore, there was an increase in the expressions of caspase-3 and -7 and poly(ADP-ribose) polymerase (PARP) fraction, while bcl-2 overexpression remained constant. In particular, the alkaloids isopterpodine and pteropodine of U. tomentosa exhibited a significant pro-apoptotic effect on MTC cells, whereas the alkaloid-poor fraction inhibited cell proliferation but did not show any pro-apoptotic effects. These promising results indicate the growth-restraining and apoptotic potential of plant extracts against neuroendocrine tumors, which may add to existing therapies for cancer. PMID:20032400

  7. Antiproliferative and pro-apoptotic effects of Uncaria tomentosa in human medullary thyroid carcinoma cells.

    Science.gov (United States)

    Rinner, Beate; Li, Zeng Xia; Haas, Helga; Siegl, Veronika; Sturm, Sonja; Stuppner, Hermann; Pfragner, Roswitha

    2009-11-01

    Medullary thyroid carcinoma (MTC), a rare calcitonin-producing tumor, is derived from parafollicular C-cells of the thyroid and is characterized by constitutive Bcl-2 overexpression. The tumor is relatively insensitive to radiation therapy as well as conventional chemotherapy. To date, the only curative treatment is the early and complete surgical removal of all neoplastic tissue. In this study, the antiproliferative and pro-apoptotic effects of fractions obtained from Uncaria tomentosa (Willd.) DC, commonly known as uña de gato or cat's claw were investigated. Cell growth of MTC cells as well as enzymatic activity of mitochondrial dehydrogenase was markedly inhibited after treatment with different fractions of the plant. Furthermore, there was an increase in the expressions of caspase-3 and -7 and poly(ADP-ribose) polymerase (PARP) fraction, while bcl-2 overexpression remained constant. In particular, the alkaloids isopterpodine and pteropodine of U. tomentosa exhibited a significant pro-apoptotic effect on MTC cells, whereas the alkaloid-poor fraction inhibited cell proliferation but did not show any pro-apoptotic effects. These promising results indicate the growth-restraining and apoptotic potential of plant extracts against neuroendocrine tumors, which may add to existing therapies for cancer.

  8. Synthesis of New Quinoxalines Containing an Oxirane Ring by the TDAE Strategy and in Vitro Evaluation in Neuroblastoma Cell Lines

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    Marc Montana

    2014-09-01

    Full Text Available Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. In order to obtain new compounds active on neuroblastoma cell lines, we investigated the reactivity of carbanion formed via TDAE in quinoxaline series. The new synthesized compounds were tested for their anti-proliferative activity on two neuroblastoma cell lines, and seven oxirane derivatives obtained interesting activities.

  9. Evaluation of the Anti-proliferative Effects of Ophiocoma erinaceus Methanol Extract Against Human Cervical Cancer Cells

    OpenAIRE

    Baharara, Javad; Amini, Elaheh; Namvar, Farideh

    2016-01-01

    Background: Marine organisms provide appreciable source of novel bioactive compounds with pharmacological potential. There is little information in correlation with anti-cancer activities of brittle star. In the present study, anti-neoplastic efficacy of Ophiocoma erinaceus methanol extract against human cervical cancer cells was investigated. Methods: The HeLa cells were cultured and exposed to brittle star methanol extract for 24 and 48 hr. The anti-proliferative properties were examined by...

  10. Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

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    Ramaswamy Nagarajan

    2008-11-01

    Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

  11. Anti-proliferative effect of leaf extracts of Eucalyptus citriodora against human cancer cells in vitro and in vivo.

    Science.gov (United States)

    Bhagat, Madhulika; Sharma, Vikas; Saxena, Ajit Kumar

    2012-12-01

    Six different extracts from Eucalyptus citriodora leaves were investigated for their anticancer effect. Extracts were prepared using a range of polar and non-polar solvents to leach out maximum active components. Phytochemical analysis of the extracts revealed the presence of anthraquinones, cardiac glycosides, flavonoids, saponins and tannins. Cytotoxic activity of different extracts was tested in vitro against seven human cancer cell lines from seven different tissues, such as SW-620 (colon), HOP-62 (lung), PC-3 (prostate), OVCAR-5 (ovary), HeLa (cervix), IMR-32 (neuroblastoma) and HEP-2 (liver). The ethyl acetate, chloroform and 50% methanolic extract displayed highest anti-proliferative effect in a dose-dependent manner. In vivo anti-tumor activity was evaluated against murine tumor (solid) model of Ehrlich ascites carcinoma and Sarcoma 180. The results showed that ethyl acetate and aqueous extracts suppressed the growth of Ehrlich ascites carcinoma (29.79% and 18.48%, respectively), but showed little growth inhibition in case of Sarcoma 180 (13. 86% and 8.57%, respectively). The activity might be due to the flavonoids, tannins and saponins that are present in all the extracts of the plant. Further investigation is required for the isolation of active principle(s) from the ethyl acetate extract, which has shown significant in vitro and in vivo anticancer potential. PMID:23350280

  12. Antiproliferative and cell apoptosis-inducing activities of compounds from Buddleja davidii in Mgc-803 cells

    Directory of Open Access Journals (Sweden)

    Wu Jian

    2012-08-01

    Full Text Available Abstract Background Buddleja davidii is widely distributed in the southwestern region of China. We have undertaken a systematic analysis of B. davidii as a Chinese traditional medicine with anticancer activity by isolating natural products for their activity against the human gastric cancer cell line Mgc-803 and the human breast cancer cell line Bcap-37. Results Ten compounds were extracted and isolated from B. davidii, among which colchicine was identified in B. davidii for the first time. The inhibitory activities of these compounds were investigated in Mgc-803, Bcap-37 cells in vitro by MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] assay, and the results showed that luteolin and colchicine had potent inhibitory activities against the growth of Mgc-803 cells. Subsequent fluorescence staining and flow cytometry analysis indicated that these two compounds could induce apoptosis in Mgc-803 cells. The results also showed that the percentages of early apoptotic cells (Annexin V+/PI-, where PI is propidium iodide and late apoptotic cells (Annexin V+/PI+ increased in a dose- and time-dependent manner. After 36 h of incubation with luteolin at 20 μM, the percentages of cells were approximately 15.4% in early apoptosis and 43.7% in late apoptosis; after 36 h of incubation with colchicine at 20 μM, the corresponding values were 7.7% and 35.2%, respectively. Conclusions Colchicine and luteolin from B. davidii have potential applications as adjuvant therapies for treating human carcinoma cells. These compounds could also induce apoptosis in tumor cells.

  13. The antiproliferative effect of indomethacin-loaded lipid-core nanocapsules in glioma cells is mediated by cell cycle regulation, differentiation, and the inhibition of survival pathways

    Directory of Open Access Journals (Sweden)

    Bernardi A

    2013-02-01

    Full Text Available Andressa Bernardi,1,* Rudimar L Frozza,2,* Juliana B Hoppe,2 Christianne Salbego,2 Adriana R Pohlmann,1,3 Ana Maria O Battastini,2 Sílvia S Guterres11Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS, Porto Alegre, RS, Brasil; 2Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brasil; 3Departamento de Química Orgânica, Instituto de Química, UFRGS, Porto Alegre, RS, Brasil *Both authors contributed equally to this workAbstract: Despite recent advances in radiotherapy, chemotherapy, and surgical techniques, glioblastoma multiforme (GBM prognosis remains dismal. There is an urgent need for new therapeutic strategies. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intense interest in recent years because they can provide sustained, controlled, and targeted delivery. Here, we investigate the mechanisms involved in the antiproliferative effect of indomethacin-loaded lipid-core nanocapsules (IndOH-LNC in glioma cells. IndOH-LNC were able to reduce cell viability by inducing apoptotic cell death in C6 and U138-MG glioma cell lines. Interestingly, IndOH-LNC did not affect the viability of primary astrocytes, suggesting that this formulation selectively targeted transformed cells. Mechanistically, IndOH-LNC induced inhibition of cell growth and cell-cycle arrest to be correlated with the inactivation of AKT and ß-catenin and the activation of GSK-3ß. IndOH-LNC also induced G0/G1 and/or G2/M phase arrest, which was accompanied by a decrease in the levels of cyclin D1, cyclin B1, pRb, and pcdc2 and an increase in the levels of Wee1 CDK inhibitor p21WAF1. Additionally, IndOH-LNC promoted GBM cell differentiation, observed as upregulation of glial fibrillary acidic protein (GFAP protein and downregulation of nestin and CD133. Taken together, the crosstalk among antiproliferative effects

  14. Antiproliferative and proapoptotic effects of somatostatin on activated hepatic stellate cells

    Institute of Scientific and Technical Information of China (English)

    Qin Pan; Ding-Guo Li; Han-Ming Lu; Liang-Yong Lu; Yu-Qin Wang; Qin-Fang Xu

    2004-01-01

    AIM: To assess the effects of somatostatin on proliferation and apoptosis of activated rat hepatic stellate cells (HSCs).METHODS: HSCs isolated from the livers of adult SpragueDawley rats (weighing 400-500 g) by in situ perfusion and purified by single-step density gradient centrifugation with Nycodenz, became activated after 10 days' cultivation. Then the apoptotic rate of HSCs treated with different doses of somatostatin for 72 h, was assayed by acridine orange/ethidium bromide fluorescent staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, transmission electron microscopy and flow cytometry, while the proliferation of HSCs was measured by MTT assay. Furthermore, the mechanisms of somatostatin were investigated by cytodynamic analysis.RESULTS: Somatostatin at the concentration of 10-6-10-9 mol/L could decrease the proliferative rate, and promote the apoptosis of activated rat HSCs in a dose-dependent way.Its action was most significant when the concentration reached 10-6 mol/L or 10-7 mol/L (P<0.05-0.01). An obvious cell-cycle arrest (G0/G1 arrest) was the important way for somatostatin to exert its action.CONCLUSION: Antiproliferative and proapoptotic effects of low-dose somatostatin on activated rat HSCs can be obtained.These findings reveal its potential antifibrotic action.

  15. Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells.

    Science.gov (United States)

    Sung, Nak Yoon; Kim, Seung Cheol; Kim, Yun Hwan; Kim, Gihyeon; Lee, Yunmi; Sung, Gi-Ho; Kim, Ji Hye; Yang, Woo Seok; Kim, Mi Seon; Baek, Kwang-Soo; Kim, Jong-Hoon; Cho, Jae Youl

    2016-07-01

    It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells. PMID:27068261

  16. Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells

    Science.gov (United States)

    Sung, Nak Yoon; Kim, Seung Cheol; Kim, Yun Hwan; Kim, Gihyeon; Lee, Yunmi; Sung, Gi-Ho; Kim, Ji Hye; Yang, Woo Seok; Kim, Mi Seon; Baek, Kwang-Soo; Kim, Jong-Hoon; Cho, Jae Youl

    2016-01-01

    It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells. PMID:27068261

  17. IMTA-cultivated Osmundea pinnatifida inhibited cell proliferation in MCF-7 cell line

    Directory of Open Access Journals (Sweden)

    Paulo Jorge Silva

    2014-06-01

    The antitumor potential of methanolic and dichloromethane extracts, obtained from wild and IMTA-cultivated seaweed, were evaluated on the MCF-7 cells (human breast adenocarcinoma cell line. The cell viability and the cell proliferation assays were performed according to MTT method. The viability of MCF-7 cells was not significantly reduced by the tested extracts (1 mg/ml; 24 h, remaining below 20%. However, MCF-7 cell proliferation was reduced 61% and 75% by the dichloromethane extracts (1 mg/ml; 24 h obtained from wild and IMTA-cultivated algae, respectively. The data suggests that O. pinnatifida is a promising source of new bioactive molecules with high antiproliferative properties.

  18. Antiproliferative activity of methanolic extracts from two green algae, Enteromorpha intestinalis and Rizoclonium riparium on HeLa cells

    OpenAIRE

    Paul, Subhabrata; Kundu, Rita

    2013-01-01

    Background Natural compounds can be alternative sources for finding new lead anti-cancer molecules. Marine algae have been a traditional source for bioactive compounds. Enteromorpha intestinalis and Rhizoclonium riparium are two well distributed saline/brackish water algae from Sundarbans. There’s no previous report of these two for their anti-proliferative activities. Methods Cytotoxicity of the algal methanolic extracts (AMEs) on HeLa cells were assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5...

  19. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Tao; Meng, Lingjun [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States); Tsai, Robert Y.L., E-mail: rtsai@ibt.tamhsc.edu [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States)

    2011-10-22

    Highlights: {yields} Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. {yields} Cell type-dependent synergy between MPA and anti-proliferative agents. {yields} The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. {yields} The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  20. Antiproliferative activity and apoptotic effects of Filipendula ulmaria pollen against C26 mice colon tumour cells

    Directory of Open Access Journals (Sweden)

    Mărgăoan Rodica

    2016-06-01

    Full Text Available Honeybee collected pollen exhibits high nutritional and pharmaceutical benefits for the human diet and medicine. Pollen’s antioxidant, anti-ageing, anti-inflammatory, anti-atherosclerosis, and cardioprotective activity, depending on the floral origin, are well known. Recent studies proposed that pollen may also be an excellent cancer-fighting candidate, as pollen harbours high amounts of phenolic substances. In our study, Filipendula ulmaria pollen (bee collected was methanol-water extracted and used to verify its in vitro pharmacological activities on C26 mice cancer tumour cells. Three different concentrations of the extract were tested in antitumour assays. Monitoring was done after 6, 12, 24, and 48 hours. Promising results were obtained for antiproliferative and apoptotic activity of the pollen extracts, with high efficiency for the highest concentration (1 mg/mL. For both activities, time and concentration-dependent effects were observed. Pollen extracts or bee collected pollen has a high potential as an antitumour agent for use in human medicine, because they are both rich in bioactive compounds.

  1. Potent Antiproliferative Effect on Liver Cancer of Medicinal Plants Selected from the Thai/Lanna Medicinal Plant Recipe Database “MANOSROI III”

    OpenAIRE

    Aranya Manosroi; Hiroyuki Akazawa; Worapong Kitdamrongtham; Toshihiro Akihisa; Worapaka Manosroi; Jiradej Manosroi

    2015-01-01

    Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including liver cancer. In this study, methanolic extracts (MEs) of 23 plants were tested for antiproliferative activity on human hepatoma cell line (Hep G2) by the sulforhodamine B (SRB) assay. Nine MEs with potent antiproliferative activity (IC50 < 100 µg/mL) were obtained and further semipurified by liquid/liquid partition extraction. The semipurified fractions were tested for the antiproliferative and ...

  2. Radiosensitivity of mesothelioma cell lines

    International Nuclear Information System (INIS)

    The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters α and β of the linear quadratic model (LQ-model) and mean inactivation dose (DMID) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean α value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The α/β ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.)

  3. Design, synthesis and antiproliferative activities of diaryl urea derivatives bearing N-acylhydrazone moiety

    Institute of Scientific and Technical Information of China (English)

    Bei Zhang; Yan Fang Zhao; Xin Zhai; Wei Jie Fan; Jun Ling Ren; Chun Fu Wu; Ping Gong

    2012-01-01

    A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized.All the target compounds were evaluated for their antiproliferative activities against human leukemia cell line (HL-60),human lung adenocarcinoma epithelial cell hne (A549) and human breast cancer cell line (MDA-MB-231) in vitro by standard MTT assay.The pharmacological results indicated that some compounds exhibited promising antitumor activities.Compound lj showed the most potent antiproliferative activity against the tested three cell lines with IC50 values of 0.13 μmol/L,0.7 μ mol/L and 0.5 μmol/L,respectively.

  4. CLO : The cell line ontology

    NARCIS (Netherlands)

    Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Meehan, Terrence F.; Diehl, Alexander D.; Vempati, Uma D.; Schuerer, Stephan C.; Pang, Chao; Malone, James; Parkinson, Helen; Liu, Yue; Takatsuki, Terue; Saijo, Kaoru; Masuya, Hiroshi; Nakamura, Yukio; Brush, Matthew H.; Haendel, Melissa A.; Zheng, Jie; Stoeckert, Christian J.; Peters, Bjoern; Mungall, Christopher J.; Carey, Thomas E.; States, David J.; Athey, Brian D.; He, Yongqun

    2014-01-01

    Background: Cell lines have been widely used in biomedical research. The community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library that covers the domain of cell lines. Since its publication two years ago, significant updates have been made, including new groups joining the CLO

  5. Flowers of Camellia nitidissima cause growth inhibition, cell-cycle dysregulation and apoptosis in a human esophageal squamous cell carcinoma cell line

    Science.gov (United States)

    Dai, Lu; Li, Ji-Lin; Liang, Xin-Qiang; Li, Lin; Feng, Yan; Liu, Hai-Zhou; Wei, Wen-Er; Ning, Shu-Fang; Zhang, Li-Tu

    2016-01-01

    The present study aimed to investigate the chemo-preventive effect of Camellia nitidissima flowers water extract (CNFE) on the Eca109 human esophageal squamous cell carcinoma (ESCC) cell line. The antiproliferative effect on Eca109 cells was determined using the trypan blue exclusion assay. The effects of CNFE on apoptosis and cell cycle arrest were investigated by flow cytometry. CNFE inhibited cell growth in both a dose- and time-dependent manner in Eca109 cells. CNFE also caused dose- and time-dependent apoptosis of these cells. Treatment of cells with CNFE resulted in dose-dependent G0/G1 phase arrest of the cell cycle. The data demonstrated that CNFE serves antiproliferative effects against human ESCC Eca109 cells by inducing apoptosis and interrupting the cell cycle. These results suggested that CNFE has the potential to be a chemoprotective agent for ESCC. PMID:27314447

  6. Cytotoxic activity of new racemic and optically active N-phosphonoalkyl bicyclic β-amino acids against human malignant cell lines.

    Science.gov (United States)

    Todorov, Petar T; Wesselinova, Diana W; Pavlov, Nikola D; Martinez, Jean; Calmes, Monique; Naydenova, Emilia D

    2012-10-01

    The cytotoxic effects of novel racemic and optically active constrained N-phosphonoalkyl bicyclic β-amino acids were tested against a panel of human tumor cell lines. All of the compounds investigated exhibited different concentration-dependent antiproliferative effects against the HT-29, MDA-MB-231, HepG2 and HeLa cell lines after 24 h treatment. The most sensitive cells were the HeLa cells at various concentrations of the four compounds tested. The aminophosphonate 3 exerted the most pronounced antiproliferative effect against the HeLa cells (inhibition of the cell vitality up to 70% at 0.5 mg/ml) and was not toxic to the normal Lep3 cells at lower concentration. Furthermore, the N-phosphonophenyl derivatives 1 and 2 displayed antiproliferative effect against mainly the MDA-MB-231 tumour cells at higher concentration.

  7. Platycodin D from Platycodonis Radix enhances the anti-proliferative effects of doxorubicin on breast cancer MCF-7 and MDA-MB-231 cells

    OpenAIRE

    Tang, Zheng-Hai; Li, Ting; Gao, Hong-wei; Sun, Wen; Chen, Xiu-Ping; Wang, Yi-Tao; Lu, Jin-jian

    2014-01-01

    Background It has been demonstrated that platycodin D (PD) exhibits anti-cancer activities. This study aims to investigate the anti-proliferative effects of the combination of PD and doxorubicin (DOX) on human breast cancer cells (MCF-7 and MDA-MB-231 cells). Methods The anti-proliferative effects of different dosages of PD, DOX, and PD + DOX on MCF-7 and MDA-MB-231 cells were determined by the MTT assay. The 10 μM PD, 5 μM DOX, and 10 μM PD + 5 μM DOX induced-protein expression of apoptosis-...

  8. Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line

    OpenAIRE

    Serafim, Teresa; Oliveira, Paulo; Sardao, Vilma; Perkins, Ed; Parke, Donna; Holy, Jon

    2008-01-01

    Abstract Purpose Natural products represent a rich reservoir of potential small molecule inhibitors exhibiting antiproliferative and tumoricidal properties. An example is the isoquinoline alkaloid berberine, which is found in plants such as goldenseal (Hydrastis canadensis). Studies have shown that berberine is able to trigger apoptosis in different malignant cell lines, and can also lead to cell cycle arrest at sub-apoptotic doses. A particularly interesting feature of berberine is the fact...

  9. Alterations in Red Blood Cell Functionality Induced by an Indole Scaffold Containing a Y-Iminodiketo Moiety: Potential Antiproliferative Conditions

    Science.gov (United States)

    Scala, Angela; Ficarra, Silvana; Russo, Annamaria; Giunta, Elena; Galtieri, Antonio; Tellone, Ester

    2016-01-01

    We have recently proposed a new erythrocyte-based model of study to predict the antiproliferative effects of selected heterocyclic scaffolds. Starting from the metabolic similarity between erythrocytes and cancer cells, we have demonstrated how the metabolic derangement induced by an indolone-based compound (DPIT) could be related to its antiproliferative effects. In order to prove the validity of our biochemical approach, in the present study the effects on erythrocyte functionality of its chemical precursor (PID), whose synthesis we reported, were investigated. The influence of the tested compound on band 3 protein (B3), oxidative state, ATP efflux, caspase 3, metabolism, intracellular pH, and Ca2+ homeostasis has been evaluated. PID crosses the membrane localizing into the cytosol, increases anion exchange, induces direct caspase activation, shifts the erythrocytes towards an oxidative state, and releases less ATP than in normal conditions. Analysis of phosphatidylserine externalization shows that PID slightly induces apoptosis. Our findings indicate that, due to its unique features, erythrocyte responses to exogenous molecular stimuli can be fruitfully correlated at structurally more complex cells, such as cancer cells. Overall, our work indicates that erythrocyte is a powerful study tool to elucidate the biochemical/biological effects of selected heterocycles opening considerable perspectives in the field of drug discovery. PMID:27651854

  10. Alterations in Red Blood Cell Functionality Induced by an Indole Scaffold Containing a Y-Iminodiketo Moiety: Potential Antiproliferative Conditions

    Directory of Open Access Journals (Sweden)

    Angela Scala

    2016-01-01

    Full Text Available We have recently proposed a new erythrocyte-based model of study to predict the antiproliferative effects of selected heterocyclic scaffolds. Starting from the metabolic similarity between erythrocytes and cancer cells, we have demonstrated how the metabolic derangement induced by an indolone-based compound (DPIT could be related to its antiproliferative effects. In order to prove the validity of our biochemical approach, in the present study the effects on erythrocyte functionality of its chemical precursor (PID, whose synthesis we reported, were investigated. The influence of the tested compound on band 3 protein (B3, oxidative state, ATP efflux, caspase 3, metabolism, intracellular pH, and Ca2+ homeostasis has been evaluated. PID crosses the membrane localizing into the cytosol, increases anion exchange, induces direct caspase activation, shifts the erythrocytes towards an oxidative state, and releases less ATP than in normal conditions. Analysis of phosphatidylserine externalization shows that PID slightly induces apoptosis. Our findings indicate that, due to its unique features, erythrocyte responses to exogenous molecular stimuli can be fruitfully correlated at structurally more complex cells, such as cancer cells. Overall, our work indicates that erythrocyte is a powerful study tool to elucidate the biochemical/biological effects of selected heterocycles opening considerable perspectives in the field of drug discovery.

  11. Evaluation of antioxidant activity and antiproliferative effect of fruit juices enriched with Pycnogenol® in colon carcinoma cells. The effect of in vitro gastrointestinal digestion.

    Science.gov (United States)

    Frontela-Saseta, Carmen; López-Nicolás, Rubén; González-Bermúdez, Carlos A; Peso-Echarri, Patricia; Ros-Berruezo, Gaspar; Martínez-Graciá, Carmen; Canali, Raffaella; Virgili, Fabio

    2011-12-01

    The aim of this study was to examine the effect of in vitro gastrointestinal digestion on the antioxidant and antiproliferative effect of fruit juices enriched with Pycnogenol® (0.5 g/L) on a colon carcinoma cell line (Caco-2). The total phenolic concentration (TPC), antioxidant activity and inhibition cell growth were studied in fresh and digested pineapple juice and red fruits juice (both enriched with pine bark extract and not). After in vitro digestion the level of detectable phenolic compounds (expressed as gallic acid equivalent) was higher in both pineapple and red fruits juices enriched with Pycnogenol® than in non-enriched commercial juices (155.6 mg/100 mL vs 94.6 mg/100 mL and 478.5 mg/100 mL vs 406.9 mg/100 mL, respectively). Increased antioxidant activity (measured by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and oxygen radical absorbance capacity assay (ORAC) methods) was observed in digested enriched juices with respect to the same samples before digestion. Pycnogenol® enrichment led to a high antiproliferative effect between 24 and 72 h of incubation with undigested pineapple juice compared with the non-enriched juice. It can be concluded that enrichment of fruit juices with Pycnogenol® provides a source of phenolic compounds with high stability to in vitro gastrointestinal conditions; however, the antioxidant properties of fruit juices were affected to a different extent. PMID:21887808

  12. Evaluation of antioxidant activity and antiproliferative effect of fruit juices enriched with Pycnogenol® in colon carcinoma cells. The effect of in vitro gastrointestinal digestion.

    Science.gov (United States)

    Frontela-Saseta, Carmen; López-Nicolás, Rubén; González-Bermúdez, Carlos A; Peso-Echarri, Patricia; Ros-Berruezo, Gaspar; Martínez-Graciá, Carmen; Canali, Raffaella; Virgili, Fabio

    2011-12-01

    The aim of this study was to examine the effect of in vitro gastrointestinal digestion on the antioxidant and antiproliferative effect of fruit juices enriched with Pycnogenol® (0.5 g/L) on a colon carcinoma cell line (Caco-2). The total phenolic concentration (TPC), antioxidant activity and inhibition cell growth were studied in fresh and digested pineapple juice and red fruits juice (both enriched with pine bark extract and not). After in vitro digestion the level of detectable phenolic compounds (expressed as gallic acid equivalent) was higher in both pineapple and red fruits juices enriched with Pycnogenol® than in non-enriched commercial juices (155.6 mg/100 mL vs 94.6 mg/100 mL and 478.5 mg/100 mL vs 406.9 mg/100 mL, respectively). Increased antioxidant activity (measured by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and oxygen radical absorbance capacity assay (ORAC) methods) was observed in digested enriched juices with respect to the same samples before digestion. Pycnogenol® enrichment led to a high antiproliferative effect between 24 and 72 h of incubation with undigested pineapple juice compared with the non-enriched juice. It can be concluded that enrichment of fruit juices with Pycnogenol® provides a source of phenolic compounds with high stability to in vitro gastrointestinal conditions; however, the antioxidant properties of fruit juices were affected to a different extent.

  13. Pluripotent stem cell lines

    OpenAIRE

    Yu, Junying; Thomson, James A.

    2008-01-01

    The derivation of human embryonic stem cells 10 years ago ignited an explosion of public interest in stem cells, yet this achievement depended on prior decades of research on mouse embryonic carcinoma cells and embryonic stem cells. In turn, the recent derivation of mouse and human induced pluripotent stem cells depended on the prior studies on mouse and human embryonic stem cells. Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in vitro while ma...

  14. Antiproliferative effect of T/Tn specific Artocarpus lakoocha agglutinin (ALA) on human leukemic cells (Jurkat, U937, K562) and their imaging by QD-ALA nanoconjugate.

    Science.gov (United States)

    Chatterjee, Urmimala; Bose, Partha Pratim; Dey, Sharmistha; Singh, Tej P; Chatterjee, Bishnu P

    2008-11-01

    T/Tn specificity of Artocarpus lakoocha agglutinin (ALA), isolated from the seeds of A. lakoocha (Moraceae) fruit and a heterodimer (16 kD and 12 kD) of molecular mass 28 kD, was further confirmed by SPR analysis using T/Tn glycan containing mammalian glycoproteins. N-terminal amino acid sequence analysis of ALA showed homology at 15, 19-21, 24-27, and 29 residues with other lectin members of Moraceae family viz., Artocarpus integrifolia (jacalin) lectin, Artocarpus hirsuta lectin, and Maclura pomifera agglutinin. It is mitogenic to human PBMC and the maximum proliferation was observed at 1 ng/ml. It showed an antiproliferative effect on leukemic cells, with the highest effect toward Jurkat cells (IC(50) 13.15 ng/ml). Synthesized CdS quantum dot-ALA nanoconjugate was employed to detect the expression of T/Tn glycans on Jurkat, U937, and K562 leukemic cells surfaces as well as normal lymphocytes by fluorescence microscopy. No green fluorescence was observed with normal lymphocytes indicating that T/Tn determinants, which are recognized as human tumor associated structures were cryptic on normal lymphocyte surfaces, whereas intense green fluorescent dots appeared during imaging of leukemic cells, where such determinants were present in unmasked form. The above results indicated that QD-ALA nanoconjugate is an efficient fluorescent marker for identification of leukemic cell lines that gives rise to high quality images.

  15. The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines

    OpenAIRE

    Bajbouj Khuloud; Schulze-Luehrmann Jan; Diermeier Stefanie; Amin Amr; Schneider-Stock Regine

    2012-01-01

    Abstract Background Saffron extract, a natural product, has been shown to induce apoptosis in several tumor cell lines. Nevertheless, the p53-dependency of saffron’s mechanism of action in colon cancer remains unexplored. Material and methods In order to examine saffron’s anti-proliferative and pro-apoptotic effects in colorectal cancer cells, we treated two p53 isogenic HCT116 cell lines (HCT wildtype and HCT p53−/−) with different doses of the drug and analyzed cell proliferation and apopto...

  16. Preparation of Prunella vulgaris polysaccharide-zinc complex and its antiproliferative activity in HepG2 cells.

    Science.gov (United States)

    Li, Chao; Huang, Qiang; Xiao, Jie; Fu, Xiong; You, Lijun; Liu, Rui Hai

    2016-10-01

    Prunella vulgaris polysaccharides have been reported to have antioxidant, antitumor and immunomodulatory activities. In this study, P. vulgaris polysaccharide (P1)-zinc complex (P1-Zn) was first prepared by a facile method and its antiproliferative effect on HepG2 human hepatocellular carcinoma cells was also investigated. Results showed that P1-Zn could effectively inhibit the proliferation (98.4% inhibition rate at 500μg/mL) of HepG2 cells through induction of apoptosis, evidenced by morphological changes, chromatin condensation and G0/G1 phase cell cycle arrest. The intracellular mechanism of P1-Zn induced apoptosis was found to be the involvement of the activation of caspase-3 and -9, reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Our findings suggest that P1-Zn may be a potent candidate for human hepatocellular carcinoma treatment and prevention in functional foods and pharmacological fields. PMID:27283235

  17. Antiproliferative Activity of Fucan Nanogel

    Directory of Open Access Journals (Sweden)

    Francisco Miguel Gama

    2012-09-01

    Full Text Available Sulfated fucans comprise families of polydisperse natural polysaccharides based on sulfated l-fucose. Our aim was to investigate whether fucan nanogel induces cell-specific responses. To that end, a non toxic fucan extracted from Spatoglossum schröederi was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc formed nanosized particles. The degree of substitution with hydrophobic chains was close to 100%, as estimated by elemental analysis. SNFfuc in aqueous media had a mean diameter of 123 nm and zeta potential of −38.3 ± 0.74 mV, as measured by dynamic light scattering. Nanoparticles conserved their size for up to 70 days. SNFuc cytotoxicity was determined using the MTT assay after culturing different cell lines for 24 h. Tumor-cell (HepG2, 786, H-S5 proliferation was inhibited by 2.0%–43.7% at nanogel concentrations of 0.05–0.5 mg/mL and rabbit aorta endothelial cells (RAEC non-tumor cell line proliferation displayed inhibition of 8.0%–22.0%. On the other hand, nanogel improved Chinese hamster ovary (CHO and monocyte macrophage cell (RAW non-tumor cell line proliferation in the same concentration range. The antiproliferative effect against tumor cells was also confirmed using the BrdU test. Flow cytometric analysis revealed that the fucan nanogel inhibited 786 cell proliferation through caspase and caspase-independent mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases of the cell cycle.

  18. Foodomics study on the effects of extracellular production of hydrogen peroxide by rosemary polyphenols on the anti-proliferative activity of rosemary polyphenols against HT-29 cells.

    Science.gov (United States)

    Valdés, Alberto; García-Cañas, Virginia; Koçak, Engin; Simó, Carolina; Cifuentes, Alejandro

    2016-07-01

    A number of studies have demonstrated a strong association between the antioxidant properties of rosemary polyphenols and their chemoprotective activity. However, the prooxidant effects of rosemary polyphenols have been rarely reported. In this work, a foodomics study is performed to investigate the in vitro autooxidation of carnosic acid (CA), carnosol (CS) and a polyphenol-enriched rosemary extract (SC-RE) in cell culture conditions. The results revealed that rosemary polyphenols autooxidation in culture medium generated H2 O2 at different rates. Generated H2 O2 levels by SC-RE and CA, but not CS, were correlated with intracellular reactive oxygen species (ROS) generation in HT-29 cells, and were partially involved in their anti-proliferative effect in this cell line. These compounds also induced different effects on glutathione metabolism. Results also indicated that high extracellular H2 O2 concentrations, resulting of using high (45 μg/mL) SC-RE concentration in culture media, exerted some artifactual effects related with cell cycle, but they did not influence the expression of relevant molecular biomarkers of stress. PMID:26842614

  19. BPR1K653, a novel Aurora kinase inhibitor, exhibits potent anti-proliferative activity in MDR1 (P-gp170-mediated multidrug-resistant cancer cells.

    Directory of Open Access Journals (Sweden)

    Chun Hei Antonio Cheung

    Full Text Available BACKGROUND: Over-expression of Aurora kinases promotes the tumorigenesis of cells. The aim of this study was to determine the preclinical profile of a novel pan-Aurora kinase inhibitor, BPR1K653, as a candidate for anti-cancer therapy. Since expression of the drug efflux pump, MDR1, reduces the effectiveness of various chemotherapeutic compounds in human cancers, this study also aimed to determine whether the potency of BPR1K653 could be affected by the expression of MDR1 in cancer cells. PRINCIPAL FINDINGS: BPR1K653 specifically inhibited the activity of Aurora-A and Aurora-B kinase at low nano-molar concentrations in vitro. Anti-proliferative activity of BPR1K653 was evaluated in various human cancer cell lines. Results of the clonogenic assay showed that BPR1K653 was potent in targeting a variety of cancer cell lines regardless of the tissue origin, p53 status, or expression of MDR1. At the cellular level, BPR1K653 induced endo-replication and subsequent apoptosis in both MDR1-negative and MDR1-positive cancer cells. Importantly, it showed potent activity against the growth of xenograft tumors of the human cervical carcinoma KB and KB-derived MDR1-positive KB-VIN10 cells in nude mice. Finally, BPR1K653 also exhibited favorable pharmacokinetic properties in rats. CONCLUSIONS AND SIGNIFICANCE: BPR1K653 is a novel potent anti-cancer compound, and its potency is not affected by the expression of the multiple drug resistant protein, MDR1, in cancer cells. Therefore, BPR1K653 is a promising anti-cancer compound that has potential for the management of various malignancies, particularly for patients with MDR1-related drug resistance after prolonged chemotherapeutic treatments.

  20. Synthesis and antiproliferative evaluation of novel 2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells.

    Science.gov (United States)

    Kulabaş, Necla; Tatar, Esra; Bingöl Özakpınar, Özlem; Özsavcı, Derya; Pannecouque, Christophe; De Clercq, Erik; Küçükgüzel, İlkay

    2016-10-01

    In this study, a series of thiosemicarbazide derivatives 12-14, 1,2,4-triazol-3-thione derivatives 15-17 and compounds bearing 2-(4H-1,2,4-triazole-3-ylthio)acetamide structure 18-32 have been synthesized starting from phenolic compounds such as 2-naphthol, paracetamol and thymol. Structures and purity of the target compounds were confirmed by the use of their chromatographic and spectral data besides microanalysis. All of the synthesized new compounds 12-32 were evaluated for their anti-HIV activity. Among these compounds, three representatives 18, 19 and 25 were selected and evaluated by the National Cancer Institute (NCI) against the full panel of 60 human cancer cell lines derived from nine different cancer types. Antiproliferative effects of the selected compounds were demonstrated in human tumor cell lines K-562, A549 and PC-3. These compounds inhibited cell growth assessed by MTT assay. Compound 18, 19 and 25 exhibited anti-cancer activity with IC50 values of 5.96 μM (PC-3 cells), 7.90 μM (A549/ATCC cells) and 7.71 μM (K-562 cells), respectively. After the cell viability assay, caspase activation and Bcl-2 activity of the selected compounds were measured and the loss of mitochondrial membrane potential (MMP) was detected. Compounds 18, 19 and 25 showed a significant increase in caspase-3 activity in a dose-dependent manner. This was not observed for caspase-8 activity with compound 18 and 25, while compound 19 was significantly elevated only at the dose of 50 μM. In addition, all three compounds significantly decreased the mitochondrial membrane potential and expression of Bcl-2. PMID:27214512

  1. Enhanced antiproliferative effects of combination hexokinase II shRNA and NIS gene therapy on vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Introduction: This study was designed to determine the antiproliferative effects of combination gene therapy using sodium iodide symporter (NIS)-based radioiodine and lentivirus-mediated short hairpin RNA (shRNA) against hexokinase II (HKII) on vascular smooth muscle cells (VSMCs). Methods: A7r5 rat VSMCs were stably transfected with a dual-expression vector of NIS and Fluc (A7r5-NL cells). Functional assessment was performed by radioiodine uptake assay, luciferase assay and confocal microscopy. After exposure to lentivirus-HKII-shRNA, the 18F-FDG uptake test and HK activity assay were performed. The effects of combination therapy with 131I and lentivirus-HKII-shRNA on VSMCs were assessed with an in vitro clonogenic assay. In vivo bioluminescence and nuclear imaging were undertaken using a xenografted mouse model. Results: In vitro functional assessment confirmed expression of NIS and Fluc genes in A7r5-NL, but not in parent A7r5 cells. Transfection of lentivirus-HKII-shRNA resulted in a significant decrease in messenger RNA expression of the HKII gene, 18F-FDG uptake and HK activity. The cell survival rate of A7r5-NL decreased to 61.9% and 90.5% by single therapy with 7.4 MBq of 131I or lentivirus-HKII-shRNA, respectively, and further decreased to 42.9% by combined therapy (P99mTc pertechnetate uptake at the site of A7r5-NL cell inoculation in nude mice. Conclusion: The enhanced antiproliferative effect on VSMCs was achieved by a combination of NIS-based radioiodine and lentivirus-mediated HKII shRNA gene therapy. Successful demonstration of in vivo dual reporter gene imaging assures the potential for further application in an animal model.

  2. Antiproliferative factor decreases Akt phosphorylation and alters gene expression via CKAP4 in T24 bladder carcinoma cells

    Directory of Open Access Journals (Sweden)

    Zhang Chen-Ou

    2010-12-01

    Full Text Available Abstract Background Urinary bladder cancer is a common malignancy worldwide, and outcomes for patients with advanced bladder cancer remain poor. Antiproliferative factor (APF is a potent glycopeptide inhibitor of epithelial cell proliferation that was discovered in the urine of patients with interstitial cystitis, a disorder with bladder epithelial thinning and ulceration. APF mediates its antiproliferative activity in primary normal bladder epithelial cells via cytoskeletal associated protein 4 (CKAP4. Because synthetic asialo-APF (as-APF has also been shown to inhibit T24 bladder cancer cell proliferation at nanomolar concentrations in vitro, and because the peptide segment of APF is 100% homologous to part of frizzled 8, we determined whether CKAP4 mediates as-APF inhibition of proliferation and/or downstream Wnt/frizzled signaling events in T24 cells. Methods T24 cells were transfected with double-stranded siRNAs against CKAP4 and treated with synthetic as-APF or inactive control peptide; cells that did not undergo electroporation and cells transfected with non-target (scrambled double-stranded siRNA served as negative controls. Cell proliferation was determined by 3H-thymidine incorporation. Expression of Akt, glycogen synthase kinase 3β (GSK3β, β-catenin, p53, and matrix metalloproteinase 2 (MMP2 mRNA was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Akt, GSK-3β, MMP2, β-catenin, and p53 protein expression, plus Akt, GSK-3β, and β-catenin phosphorylation, were determined by Western blot. Results T24 cell proliferation, MMP2 expression, Akt ser473 and thr308 phosphorylation, GSK3β tyr216 phosphorylation, and β-catenin ser45/thr41 phosphorylation were all decreased by APF, whereas p53 expression, and β-catenin ser33,37/thr41 phosphorylation, were increased by APF treatment in non-electroporated and non-target siRNA-transfected cells. Neither mRNA nor total protein expression of Akt, GSK3β, or

  3. Effect of sirolimus on urinary bladder cancer T24 cell line

    Directory of Open Access Journals (Sweden)

    Oliveira Paula A

    2009-01-01

    Full Text Available Abstract Background Sirolimus is recently reported to have antitumour effects on a large variety of cancers. The present study was performed to investigate sirolimus's ability to inhibit growth in T24 bladder cancer cells. Methods T24 bladder cancer cells were treated with various concentrations of sirolimus. MTT assay was used to evaluate the proliferation inhibitory effect on T24 cell line. The viability of T24 cell line was determined by Trypan blue exclusion analysis. Results Sirolimus inhibits the growth of bladder carcinoma cells and decreases their viability. Significant correlations were found between cell proliferation and sirolimus concentration (r = 0.830; p Conclusion Sirolimus has an anti-proliferation effect on the T24 bladder carcinoma cell line. The information from our results is useful for a better understanding sirolimus's anti-proliferative activity in the T24 bladder cancer cell line.

  4. Screening antimutagenic and antiproliferative properties of extracts isolated from Jackfruit pulp (Artocarpus heterophyllus Lam).

    Science.gov (United States)

    Ruiz-Montañez, G; Burgos-Hernández, A; Calderón-Santoyo, M; López-Saiz, C M; Velázquez-Contreras, C A; Navarro-Ocaña, A; Ragazzo-Sánchez, J A

    2015-05-15

    The present focused on the study of the antimutagenic and antiproliferative potential of pulp Jackfruit (Artocarpus heterophyllus Lam) extract, using Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line M12.C3.F6 (murine B-cell lymphoma), respectively. Jackfruit pulp extract was sequentially fractionated by chromatography (RP-HPLC) and each fraction was tested for antimutagenic and antiproliferative activities. The organic extracts obtained from Jackfruit pulp reduced the number of revertants caused by aflatoxin B1 (AFB1) and proliferation of cells M12.C3.F6; a dose-response relationship was showed. Sequential RP-HPLC fractionation of the active extracts produced both antimutagenic and/or antiproliferative fractions. These results suggested that the Jackfruit contained compounds with chemoprotective properties to reduce the mutagenicity of AFB1, also proliferation of a cancer cell line. PMID:25577099

  5. Combination therapy with vemurafenib (PLX4032/RG7204 and metformin in melanoma cell lines with distinct driver mutations

    Directory of Open Access Journals (Sweden)

    Recio Juan A

    2011-05-01

    Full Text Available Abstract Background A molecular linkage between the MAPK and the LKB1-AMPK energy sensor pathways suggests that combined MAPK oncogene inhibition and metabolic modulation of AMPK would be more effective than either manipulation alone in melanoma cell lines. Materials and methods The combination of the BRAF inhibitor vemurafenib (formerly PLX4032 and metformin were tested against a panel of human melanoma cell lines with defined BRAF and NRAS mutations for effects on viability, cell cycle and apoptosis. Signaling molecules in the MAPK, PI3K-AKT and LKB1-AMPK pathways were studied by Western blot. Results Single agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status, but in one NRASQ61K mutant cell line it powerfully stimulated cell growth. Synergistic anti-proliferative effects of the combination of metformin with vemurafenib were observed in 6 out of 11 BRAFV600E mutants, including highly synergistic effects in two BRAFV600E mutant melanoma cell lines. Antagonistic effects were noted in some cell lines, in particular in BRAFV600E mutant cell lines resistant to single agent vemurafenib. Seven out of 8 BRAF wild type cell lines showed marginally synergistic anti-proliferative effects with the combination, and one cell line had highly antagonistic effects with the combination. The differential effects were not dependent on the sensitivity to each drug alone, effects on cell cycle or signaling pathways. Conclusions The combination of vemurafenib and metformin tended to have stronger anti-proliferative effects on BRAFV600E mutant cell lines. However, determinants of vemurafenib and metformin synergism or antagonism need to be understood with greater detail before any potential clinical utility of this combination.

  6. Anti-Proliferative Effects of Siegesbeckia orientalis Ethanol Extract on Human Endometrial RL-95 Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chi-Chang Chang

    2014-12-01

    Full Text Available Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer, Hep G2 (hepatoma, FaDu (pharynx squamous cancer, MDA-MB-231 (breast cancer, and especially on LNCaP (prostate cancer cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  7. Partially Purified Extracts of Sea Anemone Anemonia viridis Affect the Growth and Viability of Selected Tumour Cell Lines

    Science.gov (United States)

    Bulati, Matteo; Longo, Alessandra; Vlah, Sara; Bennici, Carmelo; Bonura, Angela; Tagliavia, Marcello; Mazzola, Salvatore

    2016-01-01

    In the last few years, marine species have been investigated for the presence of natural products with anticancer activity. Using reversed phase chromatography, low molecular weight proteins were fractionated from the sea anemone Anemonia viridis. Four different fractions were evaluated for their cytotoxic activity by means of erythrocyte haemolysis test, MTS, and LDH assays. Finally, the antiproliferative activities of three of these fractions were studied on PC3, PLC/PRF/5, and A375 human cancer cell lines. Our analysis revealed that the four fractions showed different protein contents and diverse patterns of activity towards human PBMC and cancer cell lines. Interestingly, fractions III and IV exerted cytotoxic effects on human cells. Conversely, fractions I and II displayed very low toxic effects associated with antiproliferative activities on cancer cell lines. PMID:27725939

  8. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

    Directory of Open Access Journals (Sweden)

    De Maria Ruggero

    2008-07-01

    Full Text Available Abstract Background PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. Methods In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. Results NS loaded with 3% PTX (w/w had a mean size Conclusion These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.

  9. Syntheses and Cell-Based Phenotypic Screen of Novel 7-Amino pyrido[2,3-d]pyrimidine-6-carbonitrile Derivatives as Potential Antiproliferative Agents

    Directory of Open Access Journals (Sweden)

    Yan-Ni Lin

    2012-02-01

    Full Text Available A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile derivatives was readily synthesized and their anti-proliferative activities on five types of tumor cells were evaluated through a cell-based phenotypic screening approach. Compound 3k was found to be potent on human colon cancer SW620 cells with an IC50 value of 12.5 mM. Structural optimization of compound 3k led to compound 4a with improved anti-proliferative potency on SW620 cells with an IC50 value of 6.9 mM. Further cell-cycle analyses suggested that compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.

  10. Design, synthesis and antiproliferative activity of novel 2,7-disubstituted triazolo[1,5-a]pyrimidines

    Institute of Scientific and Technical Information of China (English)

    Xin Zhai; Nan Jiang; Ke Liang Zhang; Feng Bao; Ping Gong

    2009-01-01

    In our efforts to identify novel potent anticancer agents, we synthesized a series of 2,7-disubstituted triazolo[1,5-a]pyrimidines (6-16). Their antiproliferative activity against Bel-7402, HT- 1080 and WI-38 cell lines was tested by MTT assay in vitro. Four of the compounds (9-11 and 16) displayed promising antiproliferative activity superior to gefitinib, especially compound 9. A preliminary SAR study of these derivatives was performed.

  11. Bioactive Lipidic Extracts from Octopus (Paraoctopus limaculatus: Antimutagenicity and Antiproliferative Studies

    Directory of Open Access Journals (Sweden)

    Carolina Moreno-Félix

    2013-01-01

    Full Text Available Fractions from an organic extract from fresh octopus (Paraoctopus limaculatus were studied for biological activities such as antimutagenic and antiproliferative properties using Salmonella tester strains TA98 and TA100 with metabolic activation (S9 and a cancer cell line (B-cell lymphoma, respectively. A chloroform extract obtained from octopus tentacles was sequentially fractionated using thin layer chromatography (TLC, and each fraction was tested for antimutagenic and antiproliferative activities. Organic extract reduced the number of revertants caused by aflatoxin B1 showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. Based on the results obtained, the isolated fractions obtained from octopus contain compounds with chemoprotective properties that reduce the mutagenicity of AFB1 and proliferation of cancer cell lines.

  12. Antimutagenicity and Antiproliferative Studies of Lipidic Extracts from White Shrimp (Litopenaeus vannamei

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    Carolina Moreno-Félix

    2010-11-01

    Full Text Available An organic extract from fresh shrimp (Litopenaeus vannamei was studied for antimutagenic and antiproliferative properties using Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation (S9 and a cancer cell line (B-cell lymphoma, respectively. Shrimp extract was sequentially fractionated by thin layer chromatography (TLC and each fraction was tested for antimutagenic and antiproliferative activities. Crude organic extracts obtained from shrimp reduced the number of revertants caused by aflatoxina B1, showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. These results suggested that the lipid fraction of the tested species contained compounds with chemoprotective properties that reduce the mutagenicity of AFB1 and proliferation of a cancer cell line.

  13. Antimutagenicity and Antiproliferative Studies of Lipidic Extracts from White Shrimp (Litopenaeus vannamei)

    Science.gov (United States)

    Wilson-Sanchez, Griselda; Moreno-Félix, Carolina; Velazquez, Carlos; Plascencia-Jatomea, Maribel; Acosta, Anita; Machi-Lara, Lorena; Aldana-Madrid, María-Lourdes; Ezquerra-Brauer, Josafat-Marina; Robles-Zepeda, Ramón; Burgos-Hernandez, Armando

    2010-01-01

    An organic extract from fresh shrimp (Litopenaeus vannamei) was studied for antimutagenic and antiproliferative properties using Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line (B-cell lymphoma), respectively. Shrimp extract was sequentially fractionated by thin layer chromatography (TLC) and each fraction was tested for antimutagenic and antiproliferative activities. Crude organic extracts obtained from shrimp reduced the number of revertants caused by aflatoxina B1, showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. These results suggested that the lipid fraction of the tested species contained compounds with chemoprotective properties that reduce the mutagenicity of AFB1 and proliferation of a cancer cell line. PMID:21139845

  14. Role of VDR in anti-proliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo

    OpenAIRE

    Chung, Ivy; Han, Guangzhou; Seshadri, Mukund; Gillard, Bryan M.; Yu, Wei-Dong; Barbara A Foster; Trump, Donald L.; Johnson, Candace S.

    2009-01-01

    Calcitriol (1, 25-dihydroxycholecalciferol), the major active form of vitamin D, is anti-proliferative in tumor cells and tumor-derived endothelial cells (TDEC). These actions of calcitriol are mediated at least in part by vitamin D receptor (VDR), which is expressed in many tissues including endothelial cells. To investigate the role of VDR in calcitriol effects on tumor vasculature, we established TRAMP-2 tumors subcutaneously into either VDR wild type (WT) or knockout (KO) mice. Within 30 ...

  15. Cell lines and Salmonella

    NARCIS (Netherlands)

    Jonge R de; Hendriks H; Garssen J; Universteit Utrecht, afdeling; MGB; LPI

    2001-01-01

    In human gastrointestinal disease caused by Salmonella, transepithelial migration of neutrophils follows the attachment of bacteria to epithelial tissue. This migration of neutrophils is stimulated by the release of chemokines, including interleukin-8 (Il -8), from the epithelial cells. We have dev

  16. Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells

    Directory of Open Access Journals (Sweden)

    Lean-Teik Ng

    2011-01-01

    Full Text Available Cinnamaldehyde (Cin, cinnamic acid (Ca and cinnamyl alcohol (Cal, major constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti-inflammatory, anticancer and other activities. In this study, our aim was to evaluate the antiproliferative activity of these compounds in human hepatoma Hep G2 cells and examine the effects of pifithrin-alpha (PFTα; a specific p53 inhibitor on their apoptotic signaling transduction mechanism. The antiproliferative activity was measured by XTT assay. Expression of apoptosis-related proteins was detected by western blotting. Results showed that at a concentration of 30 μM, the order of antiproliferative activity in Hep G2 cells was Cin > Ca > Cal. Cin (IC50 9.76 ± 0.67 μM demonstrated an antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC50 9.57 ± 0.61 μM. Further studies on apoptotic mechanisms of Cin showed that it downregulated the expression of Bcl-XL, upregulated CD95 (APO-1, p53 and Bax proteins, as well as cleaving the poly (ADP-ribose polymerase (PARP in a time-dependent pattern. PFTα pre-incubation significantly diminished the effect of Cin-induced apoptosis. It markedly upregulated the anti-apoptotic (Bcl-XL expression and downregulated the pro-apoptotic (Bax expression, as well as effectively blocking the CD95 (APO-1 and p53 expression, and PARP cleavage in Cin-treated cells. This study indicates that Cin was the most potent antiproliferative constituent of C. cassia, and its apoptotic mechanism in Hep G2 cells could be mediated through the p53 induction and CD95 (APO-1 signaling pathways.

  17. Antiproliferative effects of copper(II)-polypyridyl complexes in breast cancer cells through inducing apoptosis.

    Science.gov (United States)

    Salimi, Mona; Abdi, Khatereh; Kandelous, Hirsa Mostafapour; Hadadzadeh, Hassan; Azadmanesh, Kayhan; Amanzadeh, Amir; Sanati, Hassan

    2015-04-01

    Although cisplatin has been used for decades to treat human cancer, some toxic side effects and resistance are observed. Previous investigations have suggested copper complexes as a novel class of tumor-cell apoptosis inducers. The present study aimed to evaluate the anti-breast cancer activities of two polypyridyl-based copper(II) complexes, [Cu(tpy)(dppz)](NO3)2 (1) and [Cu(tptz)2](NO3)2 (2) (tpy = 2,2':6',2″-terpyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine, tptz = 2,4,6-tris(2-pyridyl)-1,3,5-triazine), using human breast adenocarcinoma cell line (MCF-7). The ability of the complexes to cleave supercoiled DNA in the presence and absence of external agents was also examined. The apoptotic activities of the complexes were assessed using flow cytometry, fluorescence microscope and western blotting analysis. Our results indicated the high DNA affinity and nuclease activity of complexes 1 and 2. The cleavage mechanisms between the complexes and plasmid DNA are likely to involve a singlet oxygen or singlet oxygen-like entity as the reactive oxygen species. Complexes 1 and 2 also significantly inhibited the proliferation of MCF-7 cells in a dose-dependent manner (IC50 values = 4.57 and 1.98 μM at 24 h, respectively). Complex 2 remarkably induced MCF-7 cells to undergo apoptosis, which was demonstrated by cell morphology, annexin-V and propidium iodide staining. The caspase cascade was activated as shown by the proteolytic cleavage of caspase-3 after treatment of MCF-7 cells with complex 2. Additionally, complex 2 significantly increased the expression of the Bax-to-Bcl-2 ratio to induce apoptosis. In conclusion, these results revealed that complex 2 may be a potential and promising chemotherapeutic agent to treat breast cancer.

  18. Thyroid cell lines in research on goitrogenesis.

    Science.gov (United States)

    Gerber, H; Peter, H J; Asmis, L; Studer, H

    1991-12-01

    Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes. PMID:1726925

  19. Synergistic Effect of Garcinol and Curcumin on Antiproliferative and Apoptotic Activity in Pancreatic Cancer Cells

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    Mansi A. Parasramka

    2012-01-01

    Full Text Available Pancreatic cancer (PaCa is a major health concern due to its aggressiveness and early metastasis. Current treatments for PaCa are limited by development of resistance against therapy. As an alternative strategy, we assessed the combinatorial effect of dietary compounds, garcinol and curcumin, on human PaCa cells (BxPC-3 and Panc-1. A significant (<0.05 dose-dependent reduction in cell viability and increase in apoptosis were observed in both cell lines as compared to untreated controls. A combination index (CI value < 1, for a two-way comparison of curcumin and garcinol, suggests synergism. The potency (Dm of the combination of garcinol and curcumin was 2 to 10 fold that of the individual agents. This indicates that curcumin and garcinol in combination exhibit a high level of synergism, with enhanced bioactivity, thereby reducing the required effective dose required for each individually. This combinatorial strategy may hold promise in future development of therapies against PaCa.

  20. Antiproliferative Effect of Rottlerin on Sk-Mel-28 Melanoma Cells.

    Science.gov (United States)

    Daveri, Elena; Valacchi, Giuseppe; Romagnoli, Roberta; Maellaro, Emilia; Maioli, Emanuela

    2015-01-01

    Melanoma is the most aggressive and chemoresistant form of skin cancer. Mutated, constitutively active B-RAF is believed to play a crucial role, although the selective B-RAF inhibition has shown poor clinical success, since phenomena of resistance usually occur, likely arising from additional genetic aberrations, such as loss of function of p53 and PTEN, overexpression of cyclin D1, hyperactivation of NF-κB, and downregulation of p21/Cip1. Since all of them are present in the Sk-Mel-28 melanoma cells, this cell line could be an ideal, albeit hard to study, model to develop new therapeutic strategies. In the current study, we tested the cytostatic action of Rottlerin on Sk-Mel-28 melanoma cells, on the basis of the known Rottlerin effects on the main proliferative signaling pathways. We presented evidence that the drug inhibits cell growth by an Akt- and p21/Cip1-independent mechanism, involving the dual inhibition of ERK and NF-κB and downregulation of cyclin D1. In addition, we found that Rottlerin increases ERK phosphorylation, but, surprisingly, this resulted in decreased ERK activity. Pull-down experiments, using Rottlerin-CNBr-conjugated Sepharose beads, revealed that Rottlerin binds to ERK, independently from its phosphorylation status. This direct interaction could in part explain the paradoxical blockage of ERK downstream signaling and growth arrest. We would like to dedicate this paper to the memory of our friend and colleague, prematurely deceased, Claudia Torricelli, who actively contributed to this project. PMID:26161122

  1. In Vitro Antiproliferative Effect of Arthrocnemum indicum Extracts on Caco-2 Cancer Cells through Cell Cycle Control and Related Phenol LC-TOF-MS Identification

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    Mondher Boulaaba

    2013-01-01

    Full Text Available This study aimed to determinate phenolic contents and antioxidant activities of the halophyte Arthrocnemum indicum shoot extracts. Moreover, the anticancer effect of this plant on human colon cancer cells and the likely underlying mechanisms were also investigated, and the major phenols were identified by LC-ESI-TOF-MS. Results showed that shoot extracts had an antiproliferative effect of about 55% as compared to the control and were characterised by substantial total polyphenol content (19 mg GAE/g DW and high antioxidant activity (IC50=40 μg/mL for DPPH test. DAPI staining revealed that these extracts decrease DNA synthesis and reduce the proliferation of Caco-2 cells which were stopped at the G2/M phase. The changes in the cell-cycle-associated proteins (cyclin B1, p38, Erk1/2, Chk1, and Chk2 correlate with the changes in cell cycle distribution. Eight phenolic compounds were also identified. In conclusion, A. indicum showed interesting antioxidant capacities associated with a significant antiproliferative effect explained by a cell cycle blocking at the G2/M phase. Taken together, these data suggest that A. indicum could be a promising candidate species as a source of anticancer molecules.

  2. Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.

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    Michelle Visagie

    Full Text Available 2-Methoxyestradiol (2ME2 is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25 μM was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.

  3. Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells.

    Science.gov (United States)

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer.

  4. LNO3 AND L3 Are Associated With Antiproliferative And Pro-Apoptotic Action In Hepatoma Cells

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    Leonardo Campos Zanelatto

    2016-06-01

    Full Text Available Abstract The identification of antitumoral substances is the focus of intense biomedical research. Two structural analogues of thalidomide, LNO3 and L3, are two synthetic compounds that might possess such antitumor properties. We evaluated the toxicological effects of these substances, including cytotoxicity, genotoxicity and induction of apoptosis in HTC cells. Additionally, the production of free radicals (nitric oxide and superoxide was investigated, and the expression of caspases genes 3, 8, and 9 were determined by RT-qPCR. The compounds exhibited cytotoxic effects that resulted in inhibited cell proliferation. LNO3 showed to be more effective and toxic than L3 in all assays. LNO3 stimulated the release of NO and superoxide, which was accompanied by the formation of peroxynitrite. Apoptosis was induced in a dose-dependent manner by both compounds; however, the expression of caspases 3, 8 and 9 was unchanged. These results suggested that L3 and LNO3 possess antiproliferative and pro-apoptotic effects in HTC cells. Additionally, although they exhibited cytotoxicity, L3 and LNO3 might be useful coadjuvants in tumor treatment studies.

  5. Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells

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    Neo Soek-Ying

    2011-01-01

    Full Text Available Abstract Background Panax notoginseng is a potential source of anticancer compounds. This study aims to investigate the effects of steaming on the chemical profile of P. notoginseng and the anti-proliferative effects of P. notoginseng on liver cancer cells. Methods Samples of powdered raw P. notoginseng roots were steamed for various durations. Extracts of the raw and steamed samples were subjected to ultra-high pressure liquid chromatography/mass spectrometry (UHPLC-MS analysis for chemical profiling. The anti-proliferative effects on three human liver cancer cells, namely SNU449, SNU182 and HepG2, were evaluated using colorimetric WST-1 assay. Results Steaming changed chromatographic and pharmacological profiles of P. notoginseng, causing differences in activities such as inhibition of cancer growth. Steamed P. notoginseng exhibited greater anti-proliferative effects against liver cancer cells (SNU449, SNU182 and HepG2 than its raw form; steaming up to 24 hours increased bioactivities. Steaming increased the concentrations of ginsenoside Rh2, Rk1, Rk3 and 20S-Rg3 and enhanced growth inhibition of liver cancer cells. Conclusion Steaming changes the chemical profile as well as anti-cancer biological activities of P. notoginseng. Steamed P. notoginseng contains potential compounds for the treatment of liver cancer.

  6. Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts

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    Carvalho João E

    2011-03-01

    Full Text Available Abstract Background Arctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts. Methods Hot and room temperature dichloromethanic, ethanolic and aqueous extracts; hydroethanolic and total aqueous extract of A. lappa roots were investigated regarding radical scavenging activity by DPPH, total phenolic content by Folin-Ciocalteau method and antiproliferative in vitro activity was evaluated in human cancer cell lines. The hydroethanolic extract analyzed by high-resolution electrospray ionization mass spectroscopy. Results Higher radical scavenging activity was found for the hydroethanolic extract. The higher phenolic contents were found for the dichloromethane, obtained both by Soxhlet and maceration extraction and hydroethanolic extracts. The HRESI-MS demonstrated the presence of arctigenin, quercetin, chlorogenic acid and caffeic acid compounds, which were identified by comparison with previous data. The dichloromethane extracts were the only extracts that exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines. Conclusions The hydroethanolic extracts exhibited the strongest free radical scavenging activity, while the highest phenolic content was observed in Soxhlet extraction. Moreover, the dichloromethanic extracts showed selective antiproliferative activity against K562, MCF-7 and 786-0 human cancer cell lines.

  7. Bioactivity-guided study of antiproliferative activities of Salvia extracts.

    Science.gov (United States)

    Janicsák, Gábor; Zupkó, István; Nikolovac, Milena T; Forgo, Peter; Vasas, Andrea; Mathé, Imre; Blunden, Gerald; Hohmann, Judit

    2011-05-01

    The cytotoxic activities of the n-hexane, chloroform and aqueous methanolic fractions prepared from the methanolic extract of the leaves of 23 Salvia taxa were studied for their cell growth-inhibitory activity against human cervix adenocarcinoma (HeLa), skin carcinoma (A431) and breast adenocarcinoma (MCF7) cells using the MTT assay. The n-hexane fractions of six Salvia taxa (S. hispanica, S. nemorosa, S. nemorosa 1. albiflora, S. pratensis, S. recognita and S. ringens) and the chloroform fraction ofS. officinalis 1. albiflora produced over 50% growth inhibition of the skin carcinoma cell line. None of the tested extracts showed substantial (above 50%) antiproliferative effects against HeLa and MCF7 cells. S. ringens was the most powerful among the studied Salvia species with a 61.8% cell growth inhibitory activity on A431 cells. In the case of S. ringens, other plant parts were also tested for antiproliferative effect, and the highest activities were recorded for the root extract. This was subjected to bioactivity-guided fractionation, which yielded four abietane diterpenes (royleanone, horminone, 7-O-methyl-horminone and 7-acetyl-horminone), one triterpene (erythrodiol-3-acetate) and beta-sitosterol. Horminone, 7-acetyl-horminone and erythrodiol-3-acetate displayed marked concentration-dependent antiproliferative effects, while royleanone and 7-O-methyl-horminone produced weaker activities.

  8. Experimental and theoretical study of possible correlation between the electrochemistry of canthin-6-one and the anti-proliferative activity against human cancer stem cells

    Science.gov (United States)

    Cebrián-Torrejón, G.; Doménech-Carbó, A.; Scotti, M. T.; Fournet, A.; Figadère, B.; Poupon, E.

    2015-12-01

    This work presents an approach to study the performance of novel targets able to overcome cancer stem cell chemoresistance, based on the voltammetric data for microparticulate films of natural or synthetic alkaloids from the canthin-6-one series. A comparison of this voltammetric technique with conventional solution phase electrochemistry suggests the differences in the anti-proliferative activity of canthin-6-ones could be tentatively correlated to their different capacity to generate semiquinone radical anions. These data also match theoretical calculations.

  9. New geranylated flavanones from the fruits of Paulownia catalpifolia Gong Tong with their anti-proliferative activity on lung cancer cells A549.

    Science.gov (United States)

    Gao, Tian-yang; Jin, Xing; Tang, Wen-zhao; Wang, Xiao-jing; Zhao, Yun-xue

    2015-09-01

    Three new geranylated flavanones, named as paucatalinone A (1), B (2), and isopaucatalinone B (3), were isolated from the fruits of Paulownia catalpifolia Gong Tong (Scrophulariaceae). Their structures were well determined by means of IR, MS, 1D and 2D NMR, and CD techniques. Paucatalinone A (1) is the first sample as a dimeric geranylated flavanone derivative isolated from natural products. Paucatalinone A (1) displayed good antiproliferative effects on human lung cancer cells A549 and resulted in a clear increase of the percentage of cells in G1 phase and a decrease in the percentage of cells in S and G2/M phases in comparison with control cells. PMID:26115572

  10. Antimicrobial and antiproliferative prospective of kosinostatin – a secondary metabolite isolated from Streptomyces sp.

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    Vinayagam Rambabu

    2015-12-01

    Full Text Available Cancer is a communal health hazard worldwide. The present investigation attempts to evaluate antimicrobial and anticancer potential of kosinostatin on mammary carcinoma cell line (MCF-7. The anticancer and antiproliferative activities of kosinostatin were analyzed on MCF cell line by MTT assay and cytotoxicity assays like lactate dehydrogenase (LDH and glutathione (GSH. The secondary metabolite kosinostatin exhibited its apoptotic nature by expressing p53 protein. Collectively, the results acquired from this study promise that kosinostatin shows the potent anticancer activity.

  11. Antiproliferative and pro-apoptotic effects afforded by novel Src-kinase inhibitors in human neuroblastoma cells

    International Nuclear Information System (INIS)

    Neuroblastoma (NB) is the second most common solid malignancy of childhood that usually undergoes rapid progression with a poor prognosis upon metastasis. The Src-family tyrosine kinases (SFKs) are a group of proteins involved in cancer development and invasiveness that seem to play an important role in the NB carcinogenesis. To determine cell proliferation, the growth rate was evaluated by both MTT test and cells counted. Analysis of DNA content was performed for the evaluation of the cell cycle and apoptosis. To characterize the mechanisms underlying the antiproliferative effects induced by SI 34, a novel pyrazolo-pyrimidine derivative provided with Src inhibitory activity, the involvement of some cellular pathways that are important for cell proliferation and survival was investigated by western blot assays. In particular, the contribution of cyclins, Src and ERK were examined. Finally, experiments of cell adhesion and invasiveness were performed. Treatment of SH-SY5Y human NB cells and CHP100 human neuroepithelioma (NE) cultures with three novel pyrazolo[3,4-d]pyrimidine derivatives, namely SI 34, SI 35 and SI 83, inhibits the cell proliferation in a time and concentration-dependent manner. The maximal effect was obtained after 72 hours incubation with SI 34 10 μM. Fluorescence microscopy experiments, flow cytometry analysis and determination of caspase-3 activity by fluorimetric assays showed that SI 34 induced SH-SY5Y apoptosis. Moreover, SI 34 determined cell cycle arrest at the G0/G1 phase, paralleled by a decreased expression of cyclin D1. Furthermore, our data indicate that SI 34 reduces the SH-SY5Y cells adhesion and invasiveness. Evidence that SI 34 inhibits the Src and the ERK-phosphorylation, suggests the mechanism through which it exerts its effects in SH-SY5Y cells. Our study shows the ability of this pyrazolo-pyrimidine Src inhibitor in reducing the growth and the invasiveness of human NB cells, suggesting a promising role as novel drug in the

  12. Aroylhydrazone iron chelators: Tuning antioxidant and antiproliferative properties by hydrazide modifications.

    Science.gov (United States)

    Hrušková, Kateřina; Potůčková, Eliška; Hergeselová, Tereza; Liptáková, Lucie; Hašková, Pavlína; Mingas, Panagiotis; Kovaříková, Petra; Šimůnek, Tomáš; Vávrová, Kateřina

    2016-09-14

    Aroylhydrazones such as salicylaldehyde isonicotinoyl hydrazone (SIH) are tridentate iron chelators that may possess antioxidant and/or antineoplastic activities. Their main drawback, their low stability in plasma, has recently been partially overcome by exchanging the aldimine hydrogen for an unbranched alkyl group. In this study, ten analogs of methyl- and ethyl-substituted SIH derivatives with modified hydrazide scaffolds were synthesized to further explore their structure-activity relationships. Their iron-chelation efficiencies, anti- or pro-oxidant potentials, abilities to induce protection against model oxidative injury on the H9c2 cell line derived from rat embryonic cardiac tissue, cytotoxicities on the same H9c2 cells and antiproliferative activities on MCF-7 human breast adenocarcinoma and HL-60 human promyelotic leukemia cell lines were evaluated. Compounds derived from lipophilic naphthyl and biphenyl hydrazides displayed highly selective antiproliferative activities against both MCF-7 and HL-60 cell lines, and they showed markedly improved stabilities in plasma compared to SIH. Of particular interest is a hydrazone prepared from 2-hydroxypropiophenone and pyridazin-4-carbohydrazide that showed a considerable antiproliferative effect and protected cardiomyoblasts against oxidative stress with a five-fold higher selectivity compared to the parent compound SIH. Thus, this work highlighted new structure-activity relationships among antiproliferative and antioxidant aroylhydrazones and identified new lead compounds for further development. PMID:27187862

  13. In Vitro Antimicrobial and Antiproliferative Activity of Amphipterygium adstringens

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    A. Rodriguez-Garcia

    2015-01-01

    Full Text Available Amphipterygium adstringens is a plant widely used in Mexican traditional medicine for its known anti-inflammatory and antiulcer properties. In this work, we evaluated the in vitro antimicrobial and antiproliferative activities of the methanolic extract of A. adstringens against oral pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Candida albicans, and Candida dubliniensis, using microdilution (MIC and agar diffusion methods (MBC, and the antiproliferative activity evaluating total growth inhibition (TGI by staining the protein content with sulforhodamine B (SRB, using nine human cancer cell lines. Crude extract (CE of A. adstringens showed some degree of activity against one or more of the strains with a MIC from 0.125 mg/mL to 63 mg/mL and MBC from 1.6 to 6.3 mg/mL and cytotoxic activity, particularly against NCI-ADR/RES, an ovarian cell line expressing multiple resistance drugs phenotype. The CE is a complex mixture of possible multitarget metabolites that could be responsible for both antimicrobial and antiproliferative activities, and further investigation is required to elucidate the identity of active compounds. Nevertheless the CE itself is useful in the development of new antimicrobial treatment based on natural products to prevent oral diseases and as alternative natural source for cancer treatment and prevention.

  14. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.

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    Maruša Rajh

    Full Text Available Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with

  15. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Rajh, Maruša; Dolinar, Klemen; Miš, Katarina; Pavlin, Mojca; Pirkmajer, Sergej

    2016-01-01

    Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L) medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG) reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with 2-DG and

  16. New sesquiterpene lactones, vernonilides A and B, from the seeds of Vernonia anthelmintica in Uyghur and their antiproliferative activities.

    Science.gov (United States)

    Ito, Takuya; Aimaiti, Simayijiang; Win, Nwet Nwet; Kodama, Takeshi; Morita, Hiroyuki

    2016-08-01

    A new guaianolide sesquiterpene lactone, vernonilide A (1), and a new elemanolide sesquiterpene lactone, vernonilide B (2), were isolated from the seeds of Vernonia anthelmintica, together with three known elemanolide sesquiterpene lactones (3-5). The structures of the isolated compounds were elucidated on the basis of physicochemical evidences. Compounds 1, 3, and 4 showed strong antiproliferative activities against three human cancer cell lines (A549, HeLa, and MDA-MB-231), with IC50 values ranging from 0.10 to 1.00μM. In addition, 5 exhibited significant antiproliferative activities against HeLa and MDA-MB-231 cells, with IC50 values ranging from 1.90 to 2.20μM. The antiproliferative activities of the acetyl derivatives 6 and 7 prepared from 4 and 3, respectively, against the three cell lines were 4-10-fold weaker than the original activities. PMID:27311895

  17. Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Judit Molnár

    2016-02-01

    Full Text Available Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1, 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13-en-12,6α-olide (2, iso-seco-tanapartholide 3-O-methyl ether (3 and 4β,15-dihydro-3-dehydrozaluzanin C (4, were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica. When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC50 values in the range 3.6–13.5 μM. Treatment with the tested compounds resulted in a cell cycle disturbance characterized by increases in the G1 and G2/M populations, while there was a decrease in the S phase. Additionally, 1–3 elicited increases in the hypodiploid (subG1 population. The compounds elicited concentration-dependent chromatin condensation and disruption of the membrane integrity, as revealed by Hoechst 33258–propidium staining. Treatment for 24 h resulted in significant increases in activity of caspases-3 and -9, indicating that the tested sesquiterpenes induced the mitochondrial pathway of apoptosis. The proapoptotic properties of the sesquiterpene lactones were additionally demonstrated withannexin V staining. Compounds 1 and 2 increased the Bax/Bcl-2 expression and decreased the expressions of CDK1 and cyclin B2, as determined at the mRNA level by means of RT-PCR. These experimental results indicate that sesquiterpene lactones may be regarded as potential starting structures for the development of novel anticancer agents.

  18. Antioxidant capacity of food mixtures is not correlated with their antiproliferative activity against MCF-7 breast cancer cells.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan; Meckling, Kelly A; Marcone, Massimo F

    2013-12-01

    Combining different foods may produce additive, synergistic, or antagonistic interactions that may modify certain physiological effects (i.e., anticancer properties). For investigating these interactions and potential synergetic combinations, thirteen foods from three categories, including fruits (raspberries, blackberries, apples, grapes), vegetables (broccoli, tomatoes, mushrooms, purple cauliflowers, onions), and legumes (soy beans, adzuki beans, red kidney beans, black beans), were evaluated for their inhibitory activity against MCF-7 breast cancer cells. Grape, onion, and adzuki bean showed maximal growth inhibition of MCF-7 from the fruit, vegetable, and legume groups, respectively. When these three foods were combined in pairs, unique interactions were observed that were not seen when individual extracts were used. Combining onion and grape resulted in a synergistic antiproliferative effect (APE) against MCF-7 compared with either onion or grape treatment alone. In contrast, combining grape and adzuki bean resulted in an antagonistic interaction. Additionally, four antioxidant assays (total phenolic contents, ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl, and oxygen radical absorbance capacity) were further used to evaluate the antioxidant capacities (AC) of individual foods and their combinations. Combining raspberry and adzuki bean extracts demonstrated synergistic AC in all four assays, but they did not show synergistic APE against the MCF-7 cells. Combining broccoli and soy produced antioxidant antagonism, but did not have an antagonistic APE against MCF-7. The synergistic or antagonistic AC of food mixtures did not correlate with the synergistic or antagonistic APE against MCF-7. Further investigation is to determine the mechanisms of these interactions and to predict and enhance the therapeutic benefits of foods and food components through strategic food combinations.

  19. Antiproliferative and proapoptotic actions of okra pectin on B16F10 melanoma cells

    NARCIS (Netherlands)

    Vayssade, M.; Sengkhamparn, N.; Verhoef, R.P.; Delaigue, C.; Goundiam, O.; Vigneron, P.; Voragen, A.G.J.; Schols, H.A.; Nagel, M.D.

    2010-01-01

    The proliferation and apoptosis of metastatic melanoma cells are often abnormal. We have evaluated the action of a pectic rhamnogalacturonan obtained by hot buffer extraction of okra pods (okra RG-I) on melanoma cell growth and survival in vitro. We added okra RG-I containing an almost pure RG-I car

  20. Cytotoxic and antiproliferative activity of Securidaca longepedunculata aqueous extract on Ehrlich ascites carcinoma cells in Swiss albino mice.

    Directory of Open Access Journals (Sweden)

    R A Lawal

    2012-12-01

    Full Text Available Summary: Securidaca longepedunculata is a savannah shrub found growing in tropical Africa. It is reputed to have more than a hundred medicinal uses and is a major component of anticancer decoctions in Nigeria. An attempt was made in this study to determine the in vitro and in vivo cytotoxic activity and possible pro-apoptotic effect of Securidaca longepedunculata aqueous root bark extract on Ehrlich ascites carcinoma cells. In vitro cytotoxic activity was determined using the Trypan blue assay by incubating Ehrlich ascites carcinoma cells with various concentrations of Securidaca longepedunculata aqueous extract. In vivo study was carried out by intraperitoneal administration of varied doses of Securidaca longepedunculata to tumour-bearing mice. Isolated DNA from Ehrlich ascites carcinoma cells in treated and untreated animals was used for DNA fragmentation assay on agarose gel. Securidaca longepedunculata Aqueous extract, Securidaca longepedunculata was cytotoxic to Ehrlich ascites both in vivo and in vitro. The IC50 of Securidaca longepedunculata was 67 µg/ml. Securidaca longepedunculata caused a decrease in angiogenesis as observed in the reduction in weight of treated animals and a reduction in volume of ascitic fluid in treated mice.  DNA fragmentation assay of Ehrlich ascites carcinoma cells from treated animals depicted a possible pro-apoptotic effect of the Securidaca longepedunculata extract due to the ladder forming pattern which was comparable to that of the standard drug (fluorouracil. Securidaca longepedunculata aqueous extract had a cytotoxic and pro-apoptotic effect on Ehrlich ascites carcinoma cells. Industrial relevance: The use of Securidaca longepedunculata in traditional medicine in the treatment and management of cancer has been brought to the fore. Development of herbal drugs from the crude extracts could be achieved due to findings suggesting the plant could increase life span in patients with advanced stages of cancer

  1. Effects of berberine on proliferation, cell cycle distribution and apoptosis of human breast cancer T47D and MCF7 cell lines

    OpenAIRE

    Elmira Barzegar; Shamileh Fouladdel; Tahereh Komeili Movahhed; Shekoufeh Atashpour; Mohammad Hossein Ghahremani; Seyed Nasser Ostad; Ebrahim Azizi

    2015-01-01

    Objective(s): Berberine, a naturally occurring isoquinoline alkaloid, has shown antitumor properties in some in vitro systems. But the effect of berberine on breast cancer has not yet been completely studied. In this study, we evaluated anticancer properties of berberine in comparison to doxorubicin. Materials and Methods: The antiproliferative effects of berberine and doxorubicin alone and in combination were evaluated in T47D and MCF7 cell lines using MTT cytotoxicity assay. In addition, fl...

  2. Interlab Cell Line Collection: Bioresource of Established Human and Animal Cell Lines

    OpenAIRE

    Parodi, Barbara; Aresu, Ottavia; Visconti, Paola; Manniello, Maria Assunta; Strada, Paolo

    2015-01-01

    The Interlab Cell Line Collection (ICLC) was established in 1994 as a core facility of the National Institute of Cancer Research. It supplies: human and animal cell lines; Short Tandem Repeat (STR) profiling of human cell lines; quality control service; mycoplasma detection and eradication service; safe deposit service and patent deposit service of cell lines and hybridomas. The catalogue of services is on-line, and the cell lines are distributed all over the world. 

  3. Anti-Proliferative Effect of Copper Oxide Nanorods Against Human Cervical Carcinoma Cells.

    Science.gov (United States)

    Pandurangan, Muthuraman; Nagajyothi, P C; Shim, Jaesool; Kim, Doo Hwan

    2016-09-01

    Metal oxide nanoparticles have been widely investigated for its use in the pharmacological field. The present study was aimed to investigate the cytotoxicity of copper oxide nanorods in human cervical carcinoma cells. The effect of copper oxide nanorods on cell viability was determined by sulforhodamine-B (SRB) assay. The fluorescence and confocal microscopy analyzes showed the cell rounding and nuclear fragmentation following exposure of copper oxide nanorods. Reactive oxygen species (ROS) was increased and could initiate membrane lipid peroxidation, which in turn regulate cytokinetic movements of cells. The messenger RNA (mRNA) expression of p53 and caspase 3 was increased, which further confirms the occurrence of apoptosis at the transcriptional level. Furthermore, caspase-3 enzyme activity was increased, which also confirms the occurrence of apoptosis in tumor cells at the translational level. Taking all our experimental results together, it may suggest that the copper oxide nanorods could be a potential anti-tumor agent to inhibit cancer cell proliferation. PMID:26811107

  4. Mitochondria-Targeted Analogues of Metformin Exhibit Enhanced Antiproliferative and Radiosensitizing Effects in Pancreatic Cancer Cells.

    Science.gov (United States)

    Cheng, Gang; Zielonka, Jacek; Ouari, Olivier; Lopez, Marcos; McAllister, Donna; Boyle, Kathleen; Barrios, Christy S; Weber, James J; Johnson, Bryon D; Hardy, Micael; Dwinell, Michael B; Kalyanaraman, Balaraman

    2016-07-01

    Metformin (Met) is an approved antidiabetic drug currently being explored for repurposing in cancer treatment based on recent evidence of its apparent chemopreventive properties. Met is weakly cationic and targets the mitochondria to induce cytotoxic effects in tumor cells, albeit not very effectively. We hypothesized that increasing its mitochondria-targeting potential by attaching a positively charged lipophilic substituent would enhance the antitumor activity of Met. In pursuit of this question, we synthesized a set of mitochondria-targeted Met analogues (Mito-Mets) with varying alkyl chain lengths containing a triphenylphosphonium cation (TPP(+)). In particular, the analogue Mito-Met10, synthesized by attaching TPP(+) to Met via a 10-carbon aliphatic side chain, was nearly 1,000 times more efficacious than Met at inhibiting cell proliferation in pancreatic ductal adenocarcinoma (PDAC). Notably, in PDAC cells, Mito-Met10 potently inhibited mitochondrial complex I, stimulating superoxide and AMPK activation, but had no effect in nontransformed control cells. Moreover, Mito-Met10 potently triggered G1 cell-cycle phase arrest in PDAC cells, enhanced their radiosensitivity, and more potently abrogated PDAC growth in preclinical mouse models, compared with Met. Collectively, our findings show how improving the mitochondrial targeting of Met enhances its anticancer activities, including aggressive cancers like PDAC in great need of more effective therapeutic options. Cancer Res; 76(13); 3904-15. ©2016 AACR. PMID:27216187

  5. Enhanced Antiproliferative Effect of Carboplatin in Cervical Cancer Cells Utilizing Folate-Grafted Polymeric Nanoparticles

    Science.gov (United States)

    Ji, Jing; Zuo, Ping; Wang, Yue-Ling

    2015-11-01

    Carboplatin (CRB) possesses superior anticancer effect in cervical cancer cells with lower incidence of side effects compared to that of cisplatin. However, CRB suffers from severe side effects due to undesirable tissue distributions which contribute to the low therapeutic efficacy. Here, we report a unique folic acid-conjugated chitosan-coated poly( d- l-lactideco-glycolide) (PLGA) nanoparticles (FPCC) prepared for the selective delivery of carboplatin to the cervical cancer cells. The particles were nanosized and spherical shaped with size less than cancerous, HeLa cells owing to ligand-receptor (FA-FR-α) recognition. Consistently, FPCC showed superior cytotoxic effect than any other formulations. The IC50 (concentration of the drug required to kill 50 % of the cells) value of FPCC was 0.65 μg/ml while it was 1.08, 1.56, and 2.35 μg/ml for PCC, PLGA NP, and free CRB, respectively. Consistent with the cytotoxicity assay, FPCC induced higher fraction of early as well as late apoptosis cells. Especially, FPCC induced nearly 45 % of early apoptosis cells and more than 35 % in late apoptosis. Therefore, we propose that folate-conjugated nanoparticles might have potential applications in cervical cancer therapy.

  6. Anticancer activity of ethanolic extract of propolis on AGS cell line

    Directory of Open Access Journals (Sweden)

    Amini-Sarteshnizi Nematallah

    2015-01-01

    Full Text Available Introduction: Propolis is a natural product derived from various plant resins collected by honeybees, and has been used as a folk medicine for centuries. Propolis has been reported to exhibit a broad spectrum of activities including antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, hepatoprotective, and anticancer properties. The aim of this study was to investigate the effect of ethanolic extract of propolis (EEP obtained from Dinaran area (Iran on AGS human gastric cancer cell line. Methods: The ethanolic extract of samples was obtained by ethanol 96% and pure extract was dissolved in dimethyl sulfoxide (DMSO and used for experiments. The cytotoxic effects of various concentrations of EEP on AGS cells were investigated by MTT assay test after 24, 48, and 72 hours and compared with control cells. Results: The EEP inhibited the growth and proliferation of AGS human gastric cancer cell line. The antiproliferative effects were revealed in a dose and time-dependent manner. The IC50 values were recorded as 60, 30, and 15 (μg/ml in treatment times of 24, 48 and 72 hours, respectively. Conclusion: These findings indicated that the native EEP has strong antiproliferative effects against cancerous AGS cells. Thus, propolis and related products may provide a novel approach to the chemoprevention and treatment of human gastric cancer.

  7. Solubilization of poorly soluble lichen metabolites for biological testing on cell lines.

    Science.gov (United States)

    Kristmundsdóttir, Thórdís; Jónsdóttir, Elsa; Ogmundsdóttir, Helga M; Ingólfsdóttir, Kristín

    2005-04-01

    The depside atranorin and depsidone fumarprotocetraric acid, isolated from the lichens Stereocaulon alpinum and Cetraria islandica, respectively, were chosen as prototypes for poorly soluble natural compounds in an effort to facilitate testing in pharmacological models. Solubilizing agents previously identified as being non-toxic towards a malignant leukemic (K-562) cell line and suitable for testing of anti-proliferative activity of the dibenzofuran lichen metabolite (+)-usnic acid were used in solubilization studies of the depside and depsidone. Cyclodextrin derivatives were found to be most suitable for solubilizing the lichen compounds, the greatest rise in solubility being witnessed for fumarprotocetraric acid, increasing almost 300-fold from 0.03 mg/ml in water to 8.98 mg/ml in 10% 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). Subsequently, the lichen compounds, including (+)-usnic acid, were solubilized in 10% HPbetaCD and tested for effects on three malignant human cell lines; T-47D (breast), Panc-1 (pancreas) and PC-3 (prostate) in a standard proliferation assay. Atranorin and fumarprotocetraric acid did not exhibit anti-proliferative effects but usnic acid was active against all test cell lines with EC50 values of 4.3-8.2 microg/ml. The non-toxic solubilizing agents used in this study could prove useful for pharmacological testing of other poorly soluble natural products. PMID:15784343

  8. Antiproliferative effects of anastrozole on MCF-7 human breast cancer cells in vitro are significantly enhanced by combined treatment with testosterone undecanoate.

    Science.gov (United States)

    Chen, Rong; Cui, Junwei; Wang, Qinqin; Li, Peng; Liu, Xiaoling; Hu, Hui; Wei, Wei

    2015-07-01

    The present study aimed to assess the effects of aromatase inhibitor anastrozole and testosterone undecanoate, separately and in combination, on proliferation and apoptosis in MCF-7 human breast cancer cells cultured in vitro. The effects of various concentrations of these drugs on the proliferation of MCF-7 cells were evaluated by CCK8 assay, the levels of cell apoptosis were evaluated by flow cytometry with Annexin-V/propidium iodide staining and androgen receptor (AR) protein expression was determined by western blot analysis. The results of the CCK8 assay indicated that greater antiproliferative activity was detected in the MCF-7 cells in the combined treatment groups, compared with those treated with anastrozole or testosterone undecanoate alone. Flow cytometric analysis of apoptosis revealed that treatment with a combination of the two drugs generated a higher percentage of apoptotic cells, particularly when the two drugs were applied for 48 h, compared with single drug treatment. Western blot analysis revealed a significant decrease in AR protein expression in the combined treatment groups compared with MCF7 cells treated with single drugs. The results of the present study provided evidence supporting the potential of a combination of anastrozole and testosterone undecanoate as a novel therapeutic strategy for the treatment of breast cancer. Furthermore, it was demonstrated that the antiproliferative effects of anastrozole were significantly enhanced by combined treatment with testosterone undecanoate via the AR signaling pathway. PMID:25738971

  9. Antiproliferative activity and apoptosis induction of Eucalyptus Citriodora resin and its major bioactive compound in melanoma B16F10 cells.

    Science.gov (United States)

    Duh, Pin-Der; Chen, Zong-Tsi; Lee, Shwu-Woan; Lin, Tsuey-Pin; Wang, Ya-Ting; Yen, Wen-Jye; Kuo, Ling-Feng; Chu, Heuy-Ling

    2012-08-15

    Antiproliferative activity and apoptosis induction of ethyl acetate of Eucalyptus citriodora resin (EAEER), and its major bioactive compound in melanoma B16F10 cells were investigated. 6-[1-(p-Hydroxy-phenyl)ethyl]-7-O-methyl aromadendrin (HEMA), a flavanol derivative, was isolated from EAEER and identified on the basis of its mass and NMR spectra. The results from MTT assay showed high antiproliferative effects of EAEER and HEMA on B16F10 cells. Moreover, EAEER- and HEMA-induced cell apoptosis was association with the decrease in the mitochondrial transmembrane potentials (Δψ(m)), increase in Bax/Bcl-2 ratio, and activation of caspase-3. Cells treated with EAEER and HEMA generated intracellular reactive oxygen species (ROS) and nitric oxide (NO), indicating that ROS and RNS play important roles in the induction of apoptosis in B16F10 cells. Taken together, EAEER and its major bioactive compound, HEMA, inhibited the proliferation of B16F10 cells via apoptosis and may be a potential antimelanoma agent. PMID:22838509

  10. Isolation and Identification of an Antiproliferative Compound from Fructose-Tryptophan Maillard Reaction Products.

    Science.gov (United States)

    Lee, Sang Hoon; Jeong, Su Jeong; Jang, Gwi Yeong; Kim, Min Young; Hwang, In Guk; Kim, Hyun Young; Woo, Koan Sik; Hwang, Bang Yeon; Song, Jin; Lee, Junsoo; Jeong, Heon Sang

    2016-04-20

    This study was performed to isolate and identify a compound with antiproliferative activity against human stomach cancer cell lines, from fructose-tryptophan Maillard reaction products (MRPs). The MRPs, prepared from a fructose-tryptophan solution heated at 130 °C for 2 h, were fractionated into five solvent fractions: n-hexane, chloroform, ethyl acetate, butanol, and water. The highest antiproliferative activity was found in the chloroform fraction (85.93% at 200 μg/mL), and the active compound from this chloroform fraction was purified by silica gel column chromatography, TLC, and preparative HPLC. The antiproliferative activity (IC50) of the active compound was 42.24 μg/mL, and the active compound was identified as perlolyrine (C16H10N2O2) by (1)H/(13)C NMR, DEPT, HMBC, and LC-ESI-MS. Therefore, this research may be useful in developing perlolyrine as a functional therapeutic agent. PMID:27041128

  11. Cooperative antiproliferative and differentiation-enhancing activity of medicinal plant extracts in acute myeloid leukemia cells.

    Science.gov (United States)

    Zhamanbayeva, Gulzhan T; Aralbayeva, Araylim N; Murzakhmetova, Maira K; Tuleukhanov, Sultan T; Danilenko, Michael

    2016-08-01

    Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with poor prognosis and limited treatment options. Sea buckthorn (Hippophae rhamnoides) berries, dog rose (Rosa canina) rosehips, and garden sage (Salvia officinalis) and oregano (Origanum vulgare) aerial parts are widely used in traditional medicine and exhibit antitumor effects in preclinical models. However, these plants remain scarcely tested for antileukemic activity. Here, we show that their water-ethanol leaf extracts reduced the growth and viability of AML cells and, at non-cytotoxic doses, potentiated cell differentiation induced by a low concentration of 1α,25-dihydroxyvitamin D3, the hormonal form of vitamin D, in a cell type-dependent manner. The latter effect was accompanied by upregulation of the vitamin D receptor protein components and its transcriptional activity. Furthermore, at minimally effective doses the extracts cooperated with one another to produce marked cytostatic effects associated with a partial S-phase arrest and a modest induction of apoptosis. In contrast, these combinations only slightly affected the growth and viability of proliferating normal human peripheral blood mononuclear cells. In addition, the extracts strongly inhibited microsomal lipid peroxidation and protected normal erythrocytes against hypoosmotic shock. Our results suggest that further exploration of the enhanced antileukemic effects of the combinations tested here may lead to the development of alternative therapeutic and preventive approaches against AML. PMID:27470342

  12. Cell cycle analysis and cytotoxic potential of Ruta graveolens against human tumor cell lines.

    Science.gov (United States)

    Varamini, P; Soltani, M; Ghaderi, A

    2009-01-01

    There are reports on the presence of various compounds exerting different biological activities in Ruta graveolens, a plant of Rutaceae family. The aim of the present study was to evaluate in vitro cytotoxicity of the total extract of R. graveolens against tumor cell lines of different origin. Aerial parts of the plant was extracted with 70% ethanol by sonication method and cytotoxic activity was examined on RAJI, RAMOS, RPMI8866, U937, Jurkat, MDA-MB-453, MCF-7, LNCap-FGC-10, 5637, HeLa, SK-OV-3, A549, Mehr-80 and also peripheral blood mononuclear cells (PBMC) by the use of WST-1 assay. Results were expressed as IC(50) values. R. graveolens extract showed high cytotoxic activity against RAJI and RAMOS, two Burkitt's lymphoma cell lines, with an IC(50) equal to 24.3 microg/ml and 35.2 microg/ml respectively and LNCap-FGC-10, a prostate adenocarcinoma cell line with an IC(50) equal to 27.6 microg/ml as well as Mehr-80, a newly established Large Cell Lung Carcinoma (IC(50)=46.2 microg/ml). No significant anti-proliferative activity was observed on other cell lines including MCF-7, MDA-MB-453, SK-OV-3, HeLa, 5637, JURKAT and RPMI8866. Adverse cytotoxic effect of R. graveolens was investigated against PBMCs and a significantly lower effect of this extract (IC(50)=104 microg/ml) was seen on normal cells compared with RAJI and RAMOS, two haematopoietic cell lines.

  13. Naphthoflavones as Antiproliferative Agents: Design, Synthesis and Biological Evaluation.

    Science.gov (United States)

    Kumar, Dinesh; Singh, Onkar; Nepali, Kunal; Bedi, Pms; Qayum, Arem; Singh, Shashank; Jain, Subheet K

    2016-01-01

    The present study involves the design and synthesis of naphthoflavones as antiproliferative agents. The strategy presents naphthoflavones as hybrids of naphthyl based chalcones and flavones. A panel of human cancer cell lines were employed for the cytotoxicity studies. DK-13 exhibited significant cytoxicity against MiaPaCa-2 cell lines with IC50 value of 1.93 μM and 5.63 μM against MCF-7 cell lines. The compound DK-13 was found to induce apoptosis evidenced through phase contrast microscopy, DAPI staining, and mitochondrial membrane potential loss. The cell phase distribution studies indicated an increase from 11.26 % (control sample) to 55.19 % (sample treated with 20 μM compound DK-13) in the apoptotic population. PMID:26845133

  14. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    Science.gov (United States)

    Iovine, Barbara; Oliviero, Giorgia; Garofalo, Mariangela; Orefice, Maria; Nocella, Francesca; Borbone, Nicola; Piccialli, Vincenzo; Centore, Roberto; Mazzone, Massimiliano; Piccialli, Gennaro; Bevilacqua, Maria Assunta

    2014-01-01

    In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS) production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α) as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively). Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia-related diseases. PMID

  15. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Barbara Iovine

    Full Text Available In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively. Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia

  16. Anti-Proliferative Effect of an Aqueous Extract of Prunella vulgaris in Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Sun Mi Hwang

    2013-01-01

    Full Text Available The abnormal proliferation of vascular smooth muscle cells (VSMCs in arterial walls is an important pathogenic factor of vascular disorders such as diabetic atherosclerosis. We have reported the anti-inflammatory effect of an aqueous extract from Prunella vulgaris (APV in vascular endothelial cell. In the present study, APV exhibited inhibitory effects on high glucose-stimulated VSMC proliferation, migration, and invasion activities, inducing G1 cell cycle arrest with downregulation of cyclins and CDKs and upregulation of the CKIs, p21waf1/cip1 and p27kip1. Furthermore, APV dose dependently suppressed the high glucose-induced matrix metalloproteinase activity. High glucose-induced phosphorylation of ERK, p38 MAPK, was decreased by the pretreatment of APV. NF-κB activation by high glucose was attenuated by APV, as an antioxidant. APV attenuated the high glucose-induced decrease of nuclear factor E2-related factor-2 (Nrf2 translocation and heme oxygenase-1 (HO-1 expression. Intracellular cGMP level was also increased by APV treatment. These results demonstrate that APV may inhibit VSMC proliferation via downregulating ROS/NF-κB /ERK/p38 MAPK pathways. In addition, APV has a beneficial effect by the interaction of Nrf2-mediated NO/cGMP with HO-1, suggesting that Prunella vulgaris may be useful in preventing diabetic atherosclerosis.

  17. Evaluating Antiproliferative and Antioxidant Activity of Marrubium crassidens

    Directory of Open Access Journals (Sweden)

    Sanaz Hamedeyazdan

    2014-10-01

    Full Text Available Purpose: Naturally occurring substances as novel drugs in cancer therapy, at all times, represent a challenge to science since medicinal plants are proving to be brilliant sources of new chemopreventive agents. Methods: In the present study, methanol extract from aerial parts of Marrubium crassidens was assessed for its antiproliferative activity in the breast cancer cell line MCF-7 through MTT bioassay using cell viability and cytotoxicity indices. The antioxidant property of M. crassidens extract together with its phenolic and flavonoids content were evaluated, as well. Results: According to data obtained in the study, M. crassidens exhibited antiproliferative activity with a gradual rise in cytotoxicty effect setting out on 240μg/mL concentration of the extract. Moreover, the RC50 value for antioxidant activity of the extract was determined as 40μg/mL and values for the total phenolic and flavonoids were calculated as 512.64mg gallic acid equivalent and 212.73mg quercetin equivalent per 100g of dry plant material. Conclusion: Generally, the observed antiproliferative and antioxidant properties of M. crassidens could be certified to the high amounts of phenolic and flavonoid content detected in the extract.

  18. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents

    OpenAIRE

    Sai-Yang Zhang; Dong-Jun Fu; Xiao-Xin Yue; Ying-Chao Liu; Jian Song; Hui-Hui Sun; Hong-Min Liu; Yan-Bing Zhang

    2016-01-01

    A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed t...

  19. Antiproliferative and apoptosis induction of α-mangostin in T47D breast cancer cells.

    Science.gov (United States)

    Kritsanawong, Somchai; Innajak, Sukanda; Imoto, Masaya; Watanapokasin, Ramida

    2016-05-01

    α-Mangostin extracted from mangosteen, Garcinia mangostana Linn. is known as 'queen of fruits'. The anticancer activity of α-mangostin through apoptosis induction and related signaling pathways in human breast cancer T47D cells was investigated. Human epidermal growth factor receptor 2 (HER2) and mitogen-activated protein kinase (MAPK) signaling have been shown to play important roles in apoptosis. The results showed that α-mangostin induced cell proliferation inhibition, DNA fragmentation, nuclear condensation, increased cleaved caspase-3 and cleaved caspase-9, but decreased Bcl-2 and Mcl-1 expression. Mitochondrial dysfunction and cytochrome c release were also detected. In addition, phosphorylation of ERα, HER2, PI3K, Akt and ERK1/2 were downregulated whereas p-JNK1/2 and p-p38 were upregulated. These results indicated that α-mangostin induced apoptosis associated with HER2/PI3K/Akt and MAPK signaling pathways suggesting that α-mangostin may be used as food supplement or a potential therapeutic compound for breast cancer. PMID:26892433

  20. In vivo assessment of the antiproliferative properties of interferon-alpha during immunotherapy: Ki-67 (MIB-1) in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Donskov, F; Marcussen, N; Hokland, M;

    2004-01-01

    The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-alpha) in patients with metastatic renal cell carcinoma (mRCC). Core needle biopsies of metastatic and/or the primary kidney cancer were obtained before interleukin-2 (IL-2)- and IFN.......016). Baseline or change in Ki-67 LI did not correlate to survival. These data suggest that IFN-alpha in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after 1 month of immunotherapy appears to be a significant predictor of patient survival....

  1. Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus products towards K562 erythroleukemia cells.

    Science.gov (United States)

    Kilani-Jaziri, Soumaya; Neffati, Aicha; Limem, Ilef; Boubaker, Jihed; Skandrani, Ines; Sghair, Mohamed Ben; Bouhlel, Ines; Bhouri, Wissem; Mariotte, Anne Marie; Ghedira, Kamel; Dijoux Franca, Marie-Genviève; Chekir-Ghedira, Leila

    2009-09-14

    A Total Oligomers Flavonoids (TOFs) and ethyl acetate extracts of Cyperus rotundus were analyzed, in vitro, for their antioxidant activity using several biochemical assays: the xanthine (X)/xanthine oxidase (XO), the lipid peroxidation induced by H(2)O(2) in K562 human chronic myelogenous leukemia cells and the DNA damage in pKS plasmid DNA assay induced by H(2)O(2)/UV-photolysis and for their apoptotic effect. TOF and ethyl acetate extracts were found to be efficient in inhibiting xanthine oxidase with IC(50) values of 240 and 185 microg/ml and superoxide anion with IC(50) values of 150 and 215 microg/ml, respectively. Also, all the extracts tested were effective in reducing the production of thiobarbituric acid reactive substances (TBARS) and were able to protect against H(2)O(2)/UV-photolysis induced DNA damage. The highest activity, measured as equivalents of MDA concentration, was observed in the ethyl acetate extract (MDA=2.04 nM). In addition, the data suggest that only TOF enriched extract exerts growth inhibition on K562 cells through apoptosis induction. Therefore, these extracts were subjected to further separation by chromatographic methods. Thus, three major compounds (catechin, afzelechin and galloyl quinic acid) were isolated from the TOF enriched extract and five major compounds (luteolin, ferulic acid, quercetin, 3-hydroxy, 4-methoxy-benzoic acid and 6,7-dimethoxycoumarin) from ethyl acetate extract. Their structures were determined by spectroscopic data analysis and comparison with the literature. In addition, we evaluate the biological activities of the catechin, ferulic acid and luteolin. This investigation has revealed that the luteolin was the most active in reducing the production of TBARS (MDA=1.5 nM), inhibiting significantly the proliferation of K562 cells (IC(50)=25 microg/ml) and protecting against H(2)O(2)/UV-photolysis induced DNA damage. In conclusion, the study reveals that the ability of C. rotundus to inhibit the enzyme xanthine

  2. Akacid medical formulation induces apoptosis in myeloid and lymphatic leukemic cell lines in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Hannes Neuwirt

    Full Text Available Akacid medical formulation (AMF is an oligoguanidine that exerts biocidal activity against airborne and surface microorganisms including bacteria, viruses, fungi, and molds, while showing relatively low toxicity to humans. We have previously shown that AMF exerts antiproliferative effects on a variety of solid tumor cell lines. In this study we raised the question whether AMF could also substantially inhibit cell growth or induce apoptosis in cell lines derived from hematologic malignancies such as leukemia or lymphoma. We found that AMF has antiproliferative effects on various hematologic cell lines derived from human leukemia and lymphoma. Additionally, we show that AMF induces apoptosis in leukemia cell lines not only via the extrinsic and intrinsic pathway, but also in a caspase-independent manner. This effect was found also in G0-arrested cells. Finally, in our animal experiments utilizing male nu/nu Balb/c mice we found a significant growth retardation, which was immunohistochemically associated with a significantly lower number of KI67-positive cells and caspase-3 induction in AMF-treated mice.

  3. Escin reduces cell proliferation and induces apoptosis on glioma and lung adenocarcinoma cell lines.

    Science.gov (United States)

    Çiftçi, Gülşen Akalin; Işcan, Arzu; Kutlu, Mehtap

    2015-10-01

    Aesculus hippocastanum (the horse chestnut) seed extract has a wide variety of biochemical and pharmacological effects including anti-inflammatory, antianalgesic, and antipyretic activities. The main active compound of this plant is escin. It is known that several medicinal herbs with anti-inflammatory properties have been found to have a role in the prevention and treatment of cancer. In the present study, the cytotoxic effects of escin in the C6 glioma and A549 cell lines were analyzed by MTT. Apoptotic effects of escin on both cell lines were evaluated by Annexin V binding capacity with flow cytometric analysis. Structural and ultrastructural changes were also evaluated using transmission electron microscopy. The results indicated that escin has potent antiproliferative effects against C6 glioma and A549 cells. These effects are both dose and time dependent. Taken together, escin possesses cell cycle arrest on G0/G1 phase and selective apoptotic activity on A549 cells as indicated by increased Annexin V-binding capacity, bax protein expression, caspase-3 activity and morphological changes obtained from micrographs by transmission electron microscopy. PMID:25906387

  4. Characterisation and Manipulation of Docetaxel Resistant Prostate Cancer Cell Lines

    LENUS (Irish Health Repository)

    O'Neill, Amanda J

    2011-10-07

    Abstract Background There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel. Three Docetaxel resistant sub-lines were generated and confirmed to be resistant to the apoptotic and anti-proliferative effects of increasing concentrations of Docetaxel. Results The resistant DU-145 R and 22RV1 R had expression of P-glycoprotein and its inhibition with Elacridar partially and totally reversed the resistant phenotype in the two cell lines respectively, which was not seen in the PC-3 resistant sublines. Resistance was also not mediated in the PC-3 cells by cellular senescence or autophagy but multiple changes in pro- and anti-apoptotic genes and proteins were demonstrated. Even though there were lower basal levels of NF-κB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-κB activity and IκB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells. Inhibition of NF-κB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel. Conclusion This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target.

  5. Rosmarinus officinalis essential oil: antiproliferative, antioxidant and antibacterial activities

    Directory of Open Access Journals (Sweden)

    Abdullah Ijaz Hussain

    2010-12-01

    Full Text Available The aim of this work was to investigate and compare the antiproliferative, antioxidant and antibacterial activities of Rosmarinus officinalis essential oil, native to Pakistan. The essential oil content from the leaves of R. officinalis was 0.93 g 100g-1. The GC and GC-MS analysis revealed that the major components determined in R. officinalis essential oil were 1,8-cineol (38.5%, camphor (17.1%, α-pinene (12.3%, limonene (6.23%, camphene (6.00% and linalool (5.70%. The antiproliferative activity was tested against two cancer (MCF-7 and LNCaP and one fibroblast cell line (NIH-3T3 using the MTT assay, while, the antioxidant activity was evaluated by the reduction of 2, 2-diphenyl-1-picryl hydrazyl (DPPH and measuring percent inhibition of peroxidation in linoleic acid system. The disc diffusion and modified resazurin microtitre-plate assays were used to evaluate the inhibition zones (IZ and minimum inhibitory concentration (MIC of R. officinalis essential oil, respectively. It is concluded from the results that Rosmarinus officinalis essential oil exhibited antiproliferative, antioxidant and antibacterial activities.

  6. Antioxidant and antiproliferative activity of Granny Smith apple pomace

    Directory of Open Access Journals (Sweden)

    Savatović Slađana M.

    2008-01-01

    Full Text Available Granny Smith apple pomace was subjected to evaluation as valuable source of antioxidant and anticancer phytochemicals on the basis of its content in phenolic compounds, antioxidant and antiproliferative activity. The total cotent of phenolics, flavonoids and flavan-3-ols in apple pomace determined spectrophotometrically, was 7.02 mg/g, 0.51 mg/g and 8.80 mg/g. Major phenolics (phenolic acids, flavan-3-ols, flavonoids and dihydrochalcons in apple pomace were identified and quantified by HPLC. The antioxidant activity of apple pomace on stable 1,1-diphenyl-2-picrylhydrazyl (DPPH and reactive hydroxyl radicals, was investigated by electron spin resonance (ESR spectroscopy. The IC50 DPPH and IC50 OH values of Granny Smith apple pomace were 9.51 mg/ml and 29.17 mg/ml, respectively. The antiproliferative activities of apple pomace on cervix epitheloid carcinoma (HeLa, colon adenocarcinoma (HT-29 and breast adenocarcinoma (MCF7 cell lines were determined according to the MTT (3-(4,5-dimethylthiazol-2-yl- 2,5-diphenyltetrazolium bromide colorimetric assay. The IC50 HeLa , IC50 HT-29 and IC50 MCF7 values of Granny Smith apple pomace were 26.40 mg/ml, 22.47 mg/ml and 21.26 mg/ml, respectively. The significant correlations between antioxidant activities and antiproliferative activities were established (p<0.05.

  7. New derivative of 2-(2,4-dihydroxyphenyl)thieno-1,3-thiazin-4-one (BChTT) elicits antiproliferative effect via p38-mediated cell cycle arrest in cancer cells.

    Science.gov (United States)

    Juszczak, Małgorzata; Walczak, Katarzyna; Matysiak, Joanna; Lemieszek, Marta K; Langner, Ewa; Karpińska, Monika M; Pożarowski, Piotr; Niewiadomy, Andrzej; Rzeski, Wojciech

    2016-03-15

    2-(2,4-Dihydroxyphenyl)thieno-1,3-thiazin-4-ones are a group of new compounds with potential anticancer activity. This type of derivatives was poorly investigated in the area of synthesis and biological activities. In the present study the antiproliferative action of the most active derivative BChTT was described. The aim of biological evaluation was to investigate the ability of the compound to inhibit cancer cell proliferation and identify mechanism involved in its action on the molecular level. BChTT inhibited the proliferation of lung cancer A549, colon cancer HT-29 and glioma C6 cells in the concentration-dependent manner. It was not toxic to normal cells including skin fibroblasts, hepatocytes and oligodendrocytes in the antiproliferative concentrations. BChTT decreased the DNA synthesis in the treated cancer cells and induced cell cycle arrest in the G0/G1 phase. Moreover, the ability of the compound to activate p38 kinase and decrease cyclin D1 expression was estimated. Participation of p38 kinase in the antiproliferative action of the compound was confirmed by the analysis of BChTT activity in the cells with the p38 silenced gene. The obtained results may suggest the ability of the tested derivative to inhibit cancer cells proliferation by induction of p38-mediated cyclin D1 downregulation.

  8. Quinazolinones-Phenylquinoxaline hybrids with unsaturation/saturation linkers as novel anti-proliferative agents.

    Science.gov (United States)

    Palem, Jyothsna Devi; Alugubelli, Gopi Reddy; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, S Nishanth; Bathini, Raju; Manga, Vijjulatha

    2016-07-01

    A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates. PMID:27209232

  9. Quinazolinones-Phenylquinoxaline hybrids with unsaturation/saturation linkers as novel anti-proliferative agents.

    Science.gov (United States)

    Palem, Jyothsna Devi; Alugubelli, Gopi Reddy; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, S Nishanth; Bathini, Raju; Manga, Vijjulatha

    2016-07-01

    A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates.

  10. Human Cell Line and Tissue Sample Authentication

    OpenAIRE

    Ewing, Margaret M.; McLaren, Robert S.; Hebble, Kathryn D.; Ready, Kim; Storts, Douglas R.; Hooper, Kyle

    2013-01-01

    Background: Short Tandem Repeat (STR) genotyping analysis is a proven technology for uniquely identifying virtually all human samples. STR genotyping was adopted as the preferred technology for identification of human tissue culture cell lines by the ATCC Standards Development Organization (ASN-0002: Authentication of Human Cell Lines: Standardization of STR Profiling). We developed new automation-compatible protocols/systems for generating STR profiles from human cell lines or tissue samples...

  11. Crataegus monogyna buds and fruits phenolic extracts: growth inhibitory activity on human tumor cell lines and chemical characterization by HPLC–DAD–ESI/MS

    OpenAIRE

    Rodrigues, Sandra; Ricardo C. Calhelha; Barreira, João C.M.; Dueñas, Montserrat; Carvalho, Ana Maria; Abreu, Rui M.V.; Santos-Buelga, Celestino; Ferreira, Isabel C.F.R.

    2012-01-01

    Crataegus monogyna has been extensively studied due to its various alleged health benefits. This study aimed to determine the human tumor cells growth inhibitory activity of phenolic extracts of its flower buds and fruits in three phenological stages, and further characterize the extracts by HPLC–DAD–ESI/MS. Flower bud extract showed the highest antiproliferative activity as indicated by the lowest GI50 values obtained in all the tested cell lines: MCF-7, breast adenocarcinoma; NC...

  12. Synthesis, antiproliferative activity and molecular docking of Colchicine derivatives.

    Science.gov (United States)

    Huczyński, Adam; Majcher, Urszula; Maj, Ewa; Wietrzyk, Joanna; Janczak, Jan; Moshari, Mahshad; Tuszynski, Jack A; Bartl, Franz

    2016-02-01

    In order to create more potent anticancer agents, a series of five structurally different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to β-tubulin. The experimental and computational results are in very good agreement indicating that the antimitotic activity of Colchicine derivatives can be readily predicted using computational modeling methods.

  13. Molecular Characterization of Putative Chordoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Silke Brüderlein

    2010-01-01

    Full Text Available Immortal tumor cell lines are an important model system for cancer research, however, misidentification and cross-contamination of cell lines are a common problem. Seven chordoma cell lines are reported in the literature, but none has been characterized in detail. We analyzed gene expression patterns and genomic copy number variations in five putative chordoma cell lines (U-CH1, CCL3, CCL4, GB60, and CM319. We also created a new chordoma cell line, U-CH2, and provided genotypes for cell lines for identity confirmation. Our analyses revealed that CCL3, CCL4, and GB60 are not chordoma cell lines, and that CM319 is a cancer cell line possibly derived from chordoma, but lacking expression of key chordoma biomarkers. U-CH1 and U-CH2 both have gene expression profiles, copy number aberrations, and morphology consistent with chordoma tumors. These cell lines also harbor genetic changes, such as loss of p16, MTAP, or PTEN, that make them potentially useful models for studying mechanisms of chordoma pathogenesis and for evaluating targeted therapies.

  14. HLA expression in hepatocellular carcinoma cell lines.

    Science.gov (United States)

    Wadee, A A; Paterson, A; Coplan, K A; Reddy, S G

    1994-08-01

    The present study undertook to investigate the biological significance of human leucocyte antigen expression in hepatocellular carcinoma and to elucidate the role of potential modulating agents on human leucocyte antigen expression. These studies used several hepatic tumour-derived cell lines as in vitro model systems. The cell lines included PLC/PRF/5 (Alexander cell line), Hep3B, HepG2, TONG PHC, HA22T/VGH, HA59T/VGH and Mahlavu. The cell lines K562 and Raji were used as negative and positive controls, respectively. K562, a B lymphoid-derived cell line, was shown to express negligible amounts of human leucocyte antigens, while Raji, an erythromyeloid-derived cell line, expressed both class I and class II human leucocyte antigens as well as their respective invariant chains, beta 2-microglobulin and Ii. Using an ELISA, experiments performed on these cell lines confirmed the natural expression of class I and class II antigens by the HA22T/VGH and HA59T/VGH cell lines, whereas PLC/PRF/5 displayed class II surface antigens only. The effects of modulating agents such as interferon-gamma sodium butyrate and clofazimine on human leucocyte antigen expression were investigated using the HA22T/VGH, HA59T/VGH and TONG PHC cell lines. These agents increased class II and class II human leucocyte antigen expression on HA22T/VGH and TONG PHC cells, but had no effect on the HA59T/VGH cell line. The results suggest a potential use for these agents as modulators of human leucocyte antigen expression by human heptocellular cell lines.

  15. ANTIPROLIFERATIVE ACTIVITY OF HUMAN IFN-γ-EGF3 FUSION PROTEIN ARE RELATED TO ITS EGF RECEPTOR COMPETITION

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The relationship between antiproliferative effect of human IFN-γ-EGF3 fusion protein and the influence of EGF receptor binding activity has been studied on A431 cell line. Antiproliferative activity of human IFN-γ-EGF3 was higher than that of its parent IFN-γ. In the 125 I-EGF receptor competition experiment, the inhibition of EGF receptor binding capacity on the target cells was observed in the treatments of human IFN-γ or IFN-γ-EGF3, but the later was more significant. Our data suggests that the antiproliferative effects by IFN-γ and its fusion protein are closely related to their EGF receptor competitions.

  16. Antiproliferative and Anti-Invasive Effect of Piceatannol, a Polyphenol Present in Grapes and Wine, against Hepatoma AH109A Cells

    Directory of Open Access Journals (Sweden)

    Yuichiro Kita

    2012-01-01

    Full Text Available Piceatannol is a stilbenoid, a metabolite of resveratrol found in red wine. Piceatannol and sera from rats orally given piceatannol were found to dose-dependently suppress both the proliferation and invasion of AH109A hepatoma cells in culture. Its antiproliferative effect was based on cell cycle arrest at lower concentration (25~50 μM and on apoptosis induction at higher concentration (100 μM. Piceatannol suppressed reactive oxygen species-potentiated invasive capacity by scavenging the intracellular reactive oxygen species. These results suggest that piceatannol, unlike resveratrol, has a potential to suppress the hepatoma proliferation by inducing cell cycle arrest and apoptosis induction. They also suggest that the antioxidative property of piceatannol, like resveratrol, may be involved in its anti-invasive action. Subsequently, piceatannol was found to suppress the growth of solid tumor and metastasis in hepatoma-bearing rats. Thus, piceatannol may be a useful anticancer natural product.

  17. Cytotoxic activity of kenaf (Hibiscus cannabinus L.) seed extract and oil against human cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Yu Hua Wong; Wai Yan Tan; Chin Ping Tan; Kamariah Long; Kar Lin Nyam

    2014-01-01

    Objective: To examine the cytotoxic properties of both the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cervical cancer, human breast cancer, human colon cancer and human lung cancer cell lines.Methods:kenaf seed oil on human cancer cell lines was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamine B assays. Cell morphological changes were observed by using an inverted light microscope.Results:The in vitro cytotoxic activity of the kenaf (Hibiscus cannabinus L.) seed extract and cancer cell lines. Morphological alterations in the cell lines after KSE and KSO treatment were observed. KSE and KSO possessed effective cytotoxic activities against all the cell lines been selected.Conclusions:KSE and KSO could be potential sources of natural anti-cancer agents. Further The kenaf seed extract (KSE) exhibited a lower IC50 than kenaf seed oil (KSO) in all of the investigations on using kenaf seeds for anti-proliferative properties are warranted.

  18. Cytotoxic Compounds from Juglans sinensis Dode Display Anti-Proliferative Activity by Inducing Apoptosis in Human Cancer Cells.

    Science.gov (United States)

    Lee, Yoo Jin; Cui, Jun; Lee, Jun; Han, Ah-Reum; Lee, Eun Byul; Jang, Ho Hee; Seo, Eun Kyoung

    2016-01-01

    Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3-17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1-17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer.

  19. Mycosynthesis: antibacterial, antioxidant and antiproliferative activities of silver nanoparticles synthesized from Inonotus obliquus (Chaga mushroom) extract.

    Science.gov (United States)

    Nagajyothi, P C; Sreekanth, T V M; Lee, Jae-il; Lee, Kap Duk

    2014-01-01

    In the present study, silver nanoparticles (AgNPs) were rapidly synthesized from silver nitrate solution at room temperature using Inonotus obliquus extract. The mycogenic synthesized AgNPs were characterized by UV-Visible absorption spectroscopy, Fourier transform infrared (FTIR), scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM) and atomic force microscopy (AFM). SEM revealed mostly spherical nanoparticles ranging from 14.7 to 35.2nm in size. All AgNPs concentrations showed good ABT radical scavenging activity. Further, AgNPs showed effective antibacterial activity against both gram negative and gram positive bacteria and antiproliferative activity toward A549 human lung cancer (CCL-185) and MCF-7 human breast cancer (HTB-22) cell lines. The samples demonstrated considerably high antibacterial, and antiproliferative activities against bacterial strains and cell lines. PMID:24380885

  20. Antiulcer and antiproliferative properties of spent brewer's yeast peptide extracts for incorporation into foods.

    Science.gov (United States)

    Amorim, Maria M; Pereira, Joana O; Monteiro, Karin M; Ruiz, Ana L; Carvalho, João E; Pinheiro, Hélder; Pintado, Manuela

    2016-05-18

    The main objective was to study the antiulcer and antiproliferative potential of yeast peptide extract for further incorporation into functional foods. Peptide concentrates were obtained by hydrolysis of spent brewer's yeast proteins followed by a filtration process. In order to prove the possible protection of gastric mucosa, an animal model with ulcerative lesions caused by oral administration of absolute ethanol was used. The peptide fraction extract in nine different human tumoral cell lines was tested. The results exhibited a promising antiproliferative activity against the cell line K-562 (leukemia). The results suggest that a new peptide extract can be used to develop new value-added functional food products, although further studies are required. PMID:27125503

  1. Synthesis and Antiproliferative Activity of Silybin Conjugates with Salinomycin and Monensin.

    Science.gov (United States)

    Antoszczak, Michał; Klejborowska, Greta; Kruszyk, Monika; Maj, Ewa; Wietrzyk, Joanna; Huczyński, Adam

    2015-12-01

    Aiming at development of multitarget drugs for the anticancer treatment, new silybin (SIL) conjugates with salinomycin (SAL) and monensin (MON) were synthesized, in mild esterification conditions, and their antiproliferative activity was studied. The conjugates obtained exhibit anticancer activity against HepG2, LoVo and LoVo/DX cancer cell lines. Moreover, MON-SIL conjugate exhibits higher anticancer potential and better selectivity than the corresponding SAL-SIL conjugate.

  2. In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Paula M Kustiawan; Songchan Puthong; Enos T Arung; Chanpen Chanchao

    2014-01-01

    Objective: To screen crude extracts of propolis, bee pollen and honey from four stingless bee species [Trigona incisa (T. incisa)], Timia apicalis, Trigona fusco-balteata and Trigona fuscibasis) native to East Kalimantan, Indonesia for cytotoxic activity against five human cancer cell lines (HepG2, SW620, ChaGo-I, KATO-III and BT474).Methods:All samples were extracted with methanol, and then subpartitioned with n-hexane and ethyl acetate. Each crude extract was screened at 20 µg/mL for in vitro cytotoxicity against the cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, four previously shown bioactive components from propolis (apigenin, caffeic acid phenyl ester, kaempferol and naringenin) and two chemotherapeutic drugs (doxorubicin and 5-fluorouracil) were used to evaluate the sensitivity of the cell lines.Results:Overall, crude extracts from propolis and honey had higher cytotoxic activities than bee pollen, but the activity was dependent upon the extraction solvent, bee species and cell line. Propolis extracts from T. incisa and Timia apicalis showed the highest and lowest cytotoxic activity, respectively. Only the HepG2 cell line was broadly sensitive to the honey extracts. For pure compounds, doxorubicin was the most cytotoxic, the four propolis compounds the least, but the ChaGo-I cell line was sensitive to kaempferol at 10 µg/mL and KATO-III was sensitive to kaempferol and apigenin at 10 µg/mL. All pure compounds were effective against the BT474 cell line.Conclusions:Propolis from T. incisa and Trigona fusco-balteata contain an in vitro cytotoxic activity against human cancer cell lines. Further study is required, including the isolation and characterization of the active antiproliferative agent(s).

  3. Preselection of A- and B- modified d-homo lactone and d-seco androstane derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells - QSAR approach and molecular docking analysis.

    Science.gov (United States)

    Kovačević, Strahinja Z; Podunavac-Kuzmanović, Sanja O; Jevrić, Lidija R; Vukić, Vladimir R; Savić, Marina P; Djurendić, Evgenija A

    2016-10-10

    The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d-homo lactone and d-seco androstane derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d-homo lactone and/or d-seco androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not. Also, the present paper describes the molecular docking study of 3β-acetoxy-5α,6α-epoxy- (3) and 6α,7α-epoxy-1,4-dien-3-one (24) d-homo lactone androstane derivatives, as well as 4-en-3-one (15) d-seco androstane derivative, which are compounds with strong or moderate antiproliferative activity against prostate cancer cells (PC-3), and compares them with commercially available medicament for prostate cancer - abiraterone. The obtained promising results can be used as guidelines in further syntheses of novel d-homo lactone and d-seco androstane derivatives with antiproliferative activity against breast and prostate cancer cells.

  4. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Martin Weiss

    Full Text Available One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP, is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS. In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH. Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  5. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    Science.gov (United States)

    Weiss, Martin; Gümbel, Denis; Hanschmann, Eva-Maria; Mandelkow, Robert; Gelbrich, Nadine; Zimmermann, Uwe; Walther, Reinhard; Ekkernkamp, Axel; Sckell, Axel; Kramer, Axel; Burchardt, Martin; Lillig, Christopher H; Stope, Matthias B

    2015-01-01

    One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  6. In vitro antioxidant and antiproliferative activities of plants of the ethnopharmacopeia from northwest of Mexico

    Directory of Open Access Journals (Sweden)

    Jiménez-Estrada Manuel

    2013-01-01

    Full Text Available Abstract Background The aim of this study, is to investigate the in vitro antioxidant activity, the total phenols content, the flavonoids content and the antiproliferative activity of methanolic extracts of the plants: Krameria erecta, Struthanthus palmeri, Phoradendron californicum, Senna covesii and Stegnosperma halimifolium, used by different ethnic groups from northwestern Mexico in the treatment and cure of various diseases. Methods The in vitro antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH and Ferric Reducing/Antioxidant Power assay (FRAP, the total phenols content was measured by Folin–Ciocalteau assay, the flavonoids content by the AlCl3 colorimetric method and the antiproliferative activity (line cells HeLa, RAW 264.7, M12Ak.C3.F6 and L929 using MTT method. Results The K. erecta extract showed the higher radical scavenging activity (67.88%, antioxidant activity by FRAP (1.41 mg Trolox Eq, the highest total phenols content (598.51 mg Galic Acid Eq/g extract, the highest flavonoids content (3.80 mg Quercetin Eq/g extract and the greatest antiproliferative activity in a dose dependent manner against most Cell line evaluated. A positive correlation was found between the antioxidant activity and the flavonoids content. Conclusions This study is the first report on the antioxidant and antiproliferative activities of the five species evaluated. The results demostrate that there is a positive correlation between antioxidant activity and the flavonoids content, indicating that these type of polyphenols could be the major contributors to the observed antioxidant activity in the evaluated plant extracts. Of the extracts evaluated, that of Krameria erecta showed the greatest antioxidant and antiproliferative activities, a discovery that makes this species a promising candidate for future research.

  7. In vitro antioxidant and antiproliferative activities of plants of the ethnopharmacopeia from northwest of Mexico

    Science.gov (United States)

    2013-01-01

    Background The aim of this study, is to investigate the in vitro antioxidant activity, the total phenols content, the flavonoids content and the antiproliferative activity of methanolic extracts of the plants: Krameria erecta, Struthanthus palmeri, Phoradendron californicum, Senna covesii and Stegnosperma halimifolium, used by different ethnic groups from northwestern Mexico in the treatment and cure of various diseases. Methods The in vitro antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing/Antioxidant Power assay (FRAP), the total phenols content was measured by Folin–Ciocalteau assay, the flavonoids content by the AlCl3 colorimetric method and the antiproliferative activity (line cells HeLa, RAW 264.7, M12Ak.C3.F6 and L929) using MTT method. Results The K. erecta extract showed the higher radical scavenging activity (67.88%), antioxidant activity by FRAP (1.41 mg Trolox Eq), the highest total phenols content (598.51 mg Galic Acid Eq/g extract), the highest flavonoids content (3.80 mg Quercetin Eq/g extract) and the greatest antiproliferative activity in a dose dependent manner against most Cell line evaluated. A positive correlation was found between the antioxidant activity and the flavonoids content. Conclusions This study is the first report on the antioxidant and antiproliferative activities of the five species evaluated. The results demostrate that there is a positive correlation between antioxidant activity and the flavonoids content, indicating that these type of polyphenols could be the major contributors to the observed antioxidant activity in the evaluated plant extracts. Of the extracts evaluated, that of Krameria erecta showed the greatest antioxidant and antiproliferative activities, a discovery that makes this species a promising candidate for future research. PMID:23305162

  8. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines

    Science.gov (United States)

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the “kinome”. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression. PMID:27362937

  9. Role of VDR in anti-proliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo

    Science.gov (United States)

    Chung, Ivy; Han, Guangzhou; Seshadri, Mukund; Gillard, Bryan M.; Yu, Wei-dong; Foster, Barbara A.; Trump, Donald L.; Johnson, Candace S.

    2008-01-01

    Calcitriol (1, 25-dihydroxycholecalciferol), the major active form of vitamin D, is anti-proliferative in tumor cells and tumor-derived endothelial cells (TDEC). These actions of calcitriol are mediated at least in part by vitamin D receptor (VDR), which is expressed in many tissues including endothelial cells. To investigate the role of VDR in calcitriol effects on tumor vasculature, we established TRAMP-2 tumors subcutaneously into either VDR wild type (WT) or knockout (KO) mice. Within 30 days post inoculation, tumors in KO mice were larger than those in WT (P<0.001). TDEC from WT expressed VDR and were able to transactivate a reporter gene whereas TDEC from KO mice were not. Treatment with calcitriol resulted in growth inhibition in TDEC expressing VDR. However, TDEC from KO mice were relatively resistant, suggesting that calcitriol-mediated growth inhibition on TDEC is VDR-dependent. Further analysis of the TRAMP-C2 tumor sections revealed that the vessels in KO mice were enlarged and had less pericyte coverage compared to WT (P<0.001). Contrast-enhanced MRI demonstrated an increase in vascular volume of TRAMP tumors grown in VDR KO mice compared to WT mice (P<0.001) and FITC-dextran permeability assay suggested a higher extent of vascular leakage in tumors from KO mice. Using ELISA and Western blot analysis, there was an increase of HIF-1 alpha, VEGF, Ang1 and PDGF-BB levels observed in tumors from KO mice. These results indicate that calcitriol-mediated anti-proliferative effects on TDEC are VDR dependent and loss of VDR can lead to abnormal tumor angiogenesis. PMID:19141646

  10. Novel Acylguanidine Derivatives Targeting Smoothened Induce Antiproliferative and Pro-Apoptotic Effects in Chronic Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Alessandra Chiarenza

    Full Text Available The most relevant therapeutic approaches to treat CML rely on the administration of tyrosine kinase inhibitors (TKIs like Imatinib, which are able to counteract the activity of Bcr-Abl protein increasing patient's life expectancy and survival. Unfortunately, there are some issues TKIs are not able to address; first of all TKIs are not so effective in increasing survival of patients in blast crisis, second they are not able to eradicate leukemic stem cells (LSC which represent the major cause of disease relapse, and third patients often develop resistance to TKIs due to mutations in the drug binding site. For all these reasons it's of primary interest to find alternative strategies to treat CML. Literature shows that Hedgehog signaling pathway is involved in LSC maintenance, and pharmacological inhibition of Smoothened (SMO, one of the key molecules of the pathway, has been demonstrated to reduce Bcr-Abl positive bone marrow cells and LSC. Consequently, targeting SMO could be a promising way to develop a new treatment strategy for CML overcoming the limitations of current therapies. In our work we have tested some compounds able to inhibit SMO, and among them MRT92 appears to be a very potent SMO antagonist. We found that almost all our compounds were able to reduce Gli1 protein levels in K-562 and in KU-812 CML cell lines. Furthermore, they were also able to increase Gli1 and SMO RNA levels, and to reduce cell proliferation and induce apoptosis/autophagy in both the tested cell lines. Finally, we demonstrated that our compounds were able to modulate the expression of some miRNAs related to Hedgehog pathway such as miR-324-5p and miR-326. Being Hedgehog pathway deeply implicated in the mechanisms of CML we may conclude that it could be a good therapeutic target for CML and our compounds seem to be promising antagonists of such pathway.

  11. Novel Acylguanidine Derivatives Targeting Smoothened Induce Antiproliferative and Pro-Apoptotic Effects in Chronic Myeloid Leukemia Cells

    Science.gov (United States)

    Chiarenza, Alessandra; Manetti, Fabrizio; Petricci, Elena; Ruat, Martial; Naldini, Antonella; Taddei, Maurizio; Carraro, Fabio

    2016-01-01

    The most relevant therapeutic approaches to treat CML rely on the administration of tyrosine kinase inhibitors (TKIs) like Imatinib, which are able to counteract the activity of Bcr-Abl protein increasing patient’s life expectancy and survival. Unfortunately, there are some issues TKIs are not able to address; first of all TKIs are not so effective in increasing survival of patients in blast crisis, second they are not able to eradicate leukemic stem cells (LSC) which represent the major cause of disease relapse, and third patients often develop resistance to TKIs due to mutations in the drug binding site. For all these reasons it’s of primary interest to find alternative strategies to treat CML. Literature shows that Hedgehog signaling pathway is involved in LSC maintenance, and pharmacological inhibition of Smoothened (SMO), one of the key molecules of the pathway, has been demonstrated to reduce Bcr-Abl positive bone marrow cells and LSC. Consequently, targeting SMO could be a promising way to develop a new treatment strategy for CML overcoming the limitations of current therapies. In our work we have tested some compounds able to inhibit SMO, and among them MRT92 appears to be a very potent SMO antagonist. We found that almost all our compounds were able to reduce Gli1 protein levels in K-562 and in KU-812 CML cell lines. Furthermore, they were also able to increase Gli1 and SMO RNA levels, and to reduce cell proliferation and induce apoptosis/autophagy in both the tested cell lines. Finally, we demonstrated that our compounds were able to modulate the expression of some miRNAs related to Hedgehog pathway such as miR-324-5p and miR-326. Being Hedgehog pathway deeply implicated in the mechanisms of CML we may conclude that it could be a good therapeutic target for CML and our compounds seem to be promising antagonists of such pathway. PMID:26934052

  12. Radiation of different human melanoma cell lines increased expression of RHOB. Level of this tumor suppressor gene in different cell lines

    International Nuclear Information System (INIS)

    Previous results of our group show that a correlation exists between intrinsic radiosensitivity of human melanoma cells and cell death by apoptosis. RhoB is a small GTPase that regulates cytoskeletal organization. Besides, is related to the process of apoptosis in cells exposed to DNA damage as radiation. Also, RhoB levels decrease in a wide variety of tumors with the tumor stage, being considered a tumor suppressor gene due to its antiproliferative and proapoptotic effect. The aim of this study was to analyze the expression of RhoB in different human melanoma cell lines in relation to melanocytes, and evaluate the effect of gamma radiation on the expression of RhoB. We used the A375, SB2 and Meljcell lines, and the derived from melanocytes Pig1. It was found for all three tumor lines RhoB expression levels significantly lower than those of Pig1 (p <0.05), as assessed by semiquantitative RT-PCR . When tumor cells were irradiated to a dose of 2Gyinduction was observed at 3 hours RhoB irradiation. RhoB expression increased in all lines relative to non-irradiated control, showing a greater induction ( p< 0.05) for the more radiosensitive line SB2, consistent with apoptosis in response to radiation. The results allow for the first time in melanoma demonstrate that RhoB, as well as in other tumor types, has a lower expression in tumor cells than their normal counterparts. Moreover, induction in the expression of RhoB in irradiated cells may be associated with the process of radiation-induced apoptosis. The modulation of RhoB could be a new tool to sensitize radioresistant melanoma. (author)

  13. Standards for Cell Line Authentication and Beyond

    Science.gov (United States)

    Cole, Kenneth D.; Plant, Anne L.

    2016-01-01

    Different genomic technologies have been applied to cell line authentication, but only one method (short tandem repeat [STR] profiling) has been the subject of a comprehensive and definitive standard (ASN-0002). Here we discuss the power of this document and why standards such as this are so critical for establishing the consensus technical criteria and practices that can enable progress in the fields of research that use cell lines. We also examine other methods that could be used for authentication and discuss how a combination of methods could be used in a holistic fashion to assess various critical aspects of the quality of cell lines. PMID:27300367

  14. Difference in Membrane Repair Capacity Between Cancer Cell Lines and a Normal Cell Line.

    Science.gov (United States)

    Frandsen, Stine Krog; McNeil, Anna K; Novak, Ivana; McNeil, Paul L; Gehl, Julie

    2016-08-01

    Electroporation-based treatments and other therapies that permeabilize the plasma membrane have been shown to be more devastating to malignant cells than to normal cells. In this study, we asked if a difference in repair capacity could explain this observed difference in sensitivity. Membrane repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique, providing a sensitive index of repair capacity. The normal primary cell line of all tested cell lines exhibited the slowest rate of dye entry after laser disruption and lowest level of dye uptake. Significantly, more rapid dye uptake and a higher total level of dye uptake occurred in six of the seven tested cancer cell lines (p electroporation. Viability in the primary normal cell line (98 % viable cells) was higher than in the three tested cancer cell lines (81-88 % viable cells). These data suggest more effective membrane repair in normal, primary cells and supplement previous explanations why electroporation-based therapies and other therapies permeabilizing the plasma membrane are more effective on malignant cells compared to normal cells in cancer treatment. PMID:27312328

  15. Establishment of a hamster lymphoma cell line

    Directory of Open Access Journals (Sweden)

    Abe,Shinji

    1974-08-01

    Full Text Available The establishment of a hamster lymphoma cell line was attempted. Simple mincing and trypsinization of lymphoma tissue resulted in a high degree of cell degeneration. The ascitic tumor cells produced by intraperitoneal transplantation of lymphoma tissue gave a better result. These ascitic cells grew and were cultured successively in medium consisting of RPMI 1640 and 20% fetal calf serum. Cells were round and grew in suspension. Accelerated cell growth was observed one month after starting the culture. In the stained preparations, cells were lymphoblastic. Cells were transplantable into new-born hamsters and produced tumors, but not in young adult hamsters.

  16. Enhanced in vitro antiproliferative effects of EpCAM antibody-functionalized paclitaxel-loaded PLGA nanoparticles in retinoblastoma cells

    Science.gov (United States)

    Mitra, Moutushy; Misra, Ranjita; Harilal, Anju; Sahoo, Sanjeeb K

    2011-01-01

    Background To specifically deliver paclitaxel (PTX) to retinoblastoma (RB) cells, the anionic surface-charged poly(lactic-co-glycolic acid) (PLGA) NPs loaded with paclitaxel were conjugated with epithelial cell adhesion molecule (EpCAM) antibody for enhancing site-specific intracellular delivery of paclitaxel against EpCAM overexpressing RB cells. Methods PTX-loaded PLGA NPs were prepared by the oil-in-water single emulsion solvent evaporation method, and the PTX content in NPs was estimated by the reverse phase isocratic mode of high performance liquid chromatography. Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/N-hydroxysuccinimide chemistry was employed for the covalent attachment of monoclonal EpCAM antibody onto the NP surface. In vitro cytotoxicity of native PTX, unconjugated PTX-loaded NPs (PTX-NPs), and EpCAM antibody-conjugated PTX-loaded nanoparticles (PTX-NP-EpCAM) were evaluated on a Y79 RB cell line by a dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while cellular apoptosis, cysteinyl-aspartic acid protease (caspase)-3 activation, Poly (adenosine diphosphate-ribose) polymerase (PARP) cleavage, and cell-cycle arrest were quantified by flow cytometry. By employing flow cytometry and fluorescence image analyses, the extent of cellular uptake was comparatively evaluated. Results PTX-NP-EpCAM had superior antiproliferation activity, increased arrested cell population at the G2-M phase, and increased activation of caspase-3, followed by PARP cleavage in parallel with the induction of apoptosis. Increased uptake of PTX-Np-EpCAM by the cells suggests that they were mainly taken up through EpCAM mediated endocytosis. Conclusions EpCAM antibody-functionalized biodegradable NPs for tumor-selective drug delivery and overcoming drug resistance could be an efficient therapeutic strategy for retinoblastoma treatment. PMID:22065926

  17. Identification of Target Genes Involved in the Antiproliferative Effect of Enzyme-Modified Ginseng Extract in HepG2 Hepatocarcinoma Cell

    Directory of Open Access Journals (Sweden)

    Sung-Il Jang

    2013-01-01

    Full Text Available Ginsenosides are ginseng saponins, which are the major biologically active components of Panax ginseng, often metabolized by intestinal bacteria into more effective forms. In this study, we found that the antiproliferative activity of ginseng increased after enzymatic processing of ginseng saponin (50% inhibitory concentration [IC50], >30 μg/mL, which may be the result of the accumulation of minor saponins, such as Rh1, Rg3, compound K, and PPT constituents in ginseng saponin. Using the Agilent PrimeView Human Gene Expression Array, we found that the expression of several genes involved in apoptosis (caspase-4, Annexin A2, HSPA9, AIFM1, UQCRC2, and caspase-7 were increased in HepG2 human hepatocarcinoma cells after their treatment with enzyme-modified ginseng extract (EMGE. Furthermore, several genes implicated in cell cycle progression (CDCA3, CDCA8, CABLES2, CDC25B, CNNM3, and CCNK showed decreased expression in HepG2 cells treated with EMGE. Finally, from flow cytometric analysis, we found that EMGE-treated HepG2 cells showed increased apoptotic sub-G1 population (24%, compared with that observed in DMSO-treated control cells (1.6%. Taken together, our results suggest that EMGE induces anticancer activity through the induction of apoptosis-related genes and cell cycle arrest via decreased expression of cell cycle regulatory genes.

  18. Extraction of Natural Antioxidants from the Thelephora ganbajun Mushroom by an Ultrasound-Assisted Extraction Technique and Evaluation of Antiproliferative Activity of the Extract against Human Cancer Cells

    Science.gov (United States)

    Xu, Dong-Ping; Zheng, Jie; Zhou, Yue; Li, Ya; Li, Sha; Li, Hua-Bin

    2016-01-01

    The Thelephora ganbajun mushroom has been found to be a potential rich source of natural antioxidants. In this study, an ultrasound-assisted extraction (UAE) technique together with GRAS (generally recognized as safe) solvents (ethanol and water) was used to maximize the extraction of antioxidants from Thelephora ganbajun. Five extraction parameters (ethanol concentration, solvent to solid ratio, extraction time, temperature and ultrasound power) were investigated by single-factor experiments, and then a central composite rotatable design was employed to study interaction of three key extraction parameters. The optimum conditions were as follows: 57.38% ethanol, 70.15 mL/g solvent to solid ratio, 10.58 min extraction time, 40 °C extraction temperature and 500 W ultrasound power. Under the optimum conditions, the antioxidant activity obtained was 346.98 ± 12.19 µmol Trolox/g DW, in accordance with the predicted value of 344.67 µmol Trolox/g DW. Comparison of UAE with conventional maceration and Soxhlet extraction, the UAE method showed stronger extract efficiency in a shorter extraction time. These results showed that UAE was an effective technique to extract antioxidants from Thelephora ganbajun. Furthermore, the extracts obtained under the optimized conditions exhibited antiproliferative activities toward human lung (A549), breast (MCF-7), liver (HepG2) and colon (HT-29) cancer cells, especially for liver and lung cancer cells. In addition, rutin, 2-hydrocinnamic acid and epicatechin were identified in the extract, which might contribute to antioxidant and antiproliferative activities. PMID:27706082

  19. Susceptibility of cell lines to avian viruses

    Directory of Open Access Journals (Sweden)

    Simoni Isabela Cristina

    1999-01-01

    Full Text Available The susceptibility of the five cell lines - IB-RS-2, RK-13, Vero, BHK-21, CER - to reovirus S1133 and infectious bursal disease virus (IBDV vaccine GBV-8 strain was studied to better define satisfactory and sensitive cell culture systems. Cultures were compared for presence of CPE, virus titers and detection of viral RNA. CPE and viral RNA were detected in CER and BHK-21 cells after reovirus inoculation and in RK-13 cell line after IBDV inoculation and with high virus titers. Virus replication by production of low virus titers occurred in IB-RS-2 and Vero cells with reovirus and in BHK-21 cell line with IBDV.

  20. Estrogen Receptor β Agonists Differentially Affect the Growth of Human Melanoma Cell Lines.

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    Monica Marzagalli

    Full Text Available Cutaneous melanoma is an aggressive malignancy; its incidence is increasing worldwide and its prognosis remains poor. Clinical observations indicate that estrogen receptor β (ERβ is expressed in melanoma tissues and its expression decreases with tumor progression, suggesting its tumor suppressive function. These experiments were performed to investigate the effects of ERβ activation on melanoma cell growth.Protein expression was analyzed by Western blot and immunofluorescence assays. Cell proliferation was assessed by counting the cells by hemocytometer. ERβ transcriptional activity was evaluated by gene reporter assay. Global DNA methylation was analyzed by restriction enzyme assay and ERβ isoforms were identified by qRT-PCR. We demonstrated that ERβ is expressed in a panel of human melanoma cell lines (BLM, WM115, A375, WM1552. In BLM (NRAS-mutant cells, ERβ agonists significantly and specifically inhibited cell proliferation. ERβ activation triggered its cytoplasmic-to-nuclear translocation and transcriptional activity. Moreover, the antiproliferative activity of ERβ agonists was associated with an altered expression of G1-S transition-related proteins. In these cells, global DNA was found to be hypomethylated when compared to normal melanocytes; this DNA hypomethylation status was reverted by ERβ activation. ERβ agonists also decreased the proliferation of WM115 (BRAF V600D-mutant cells, while they failed to reduce the growth of A375 and WM1552 (BRAF V600E-mutant cells. Finally, we could observe that ERβ isoforms are expressed at different levels in the various cell lines. Specific oncogenic mutations or differential expression of receptor isoforms might be responsible for the different responses of cell lines to ERβ agonists.Our results demonstrate that ERβ is expressed in melanoma cell lines and that ERβ agonists differentially regulate the proliferation of these cells. These data confirm the notion that melanoma is a

  1. Antimicrobial and antiproliferative prospective of kosinostatin-a secondary metabolite isolated from Streptomyces sp.

    Institute of Scientific and Technical Information of China (English)

    Vinayagam Rambabu; Subramaniyan Suba; Suburamaniyan Vijayakumar

    2015-01-01

    Cancer is a communal health hazard worldwide. The present investigation attempts to evaluate anti-microbial and anticancer potential of kosinostatin on mammary carcinoma cell line (MCF-7). The an-ticancer and antiproliferative activities of kosinostatin were analyzed on MCF cell line by MTT assay and cytotoxicity assays like lactate dehydrogenase (LDH) and glutathione (GSH). The secondary metabolite kosinostatin exhibited its apoptotic nature by expressing p53 protein. Collectively, the results acquired from this study promise that kosinostatin shows the potent anticancer activity.

  2. Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Falko Lange

    2014-01-01

    Full Text Available Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC patients, to evaluate effects of the small molecule kinase inhibitors (SMI vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models.

  3. Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin.

    Science.gov (United States)

    Letra-Vilela, Ricardo; Sánchez-Sánchez, Ana María; Rocha, Ana Maia; Martin, Vanesa; Branco-Santos, Joana; Puente-Moncada, Noelia; Santa-Marta, Mariana; Outeiro, Tiago Fleming; Antolín, Isaac; Rodriguez, Carmen; Herrera, Federico

    2016-10-15

    Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine. PMID:27402602

  4. Antiproliferative Activity of Flavonoids from Croton sphaerogynus Baill. (Euphorbiaceae

    Directory of Open Access Journals (Sweden)

    Kátia Pereira dos Santos

    2015-01-01

    Full Text Available Croton sphaerogynus is a shrub from the Atlantic Rain Forest in southeastern Brazil. A lyophilized crude EtOH extract from leaves of C. sphaerogynus, obtained by maceration at room temperature (seven days, was suspended in methanol and partitioned with hexane. The purified MeOH phase was fractionated over Sephadex LH-20 yielding five fractions (F1–F5 containing flavonoids, as characterized by HPLC-DAD and HPLC-MS analyses. The antiproliferative activity of the crude EtOH extract, MeOH and hexane phases, and fractions F1–F5 was evaluated on in vitro cell lines NCI-H460 (nonsmall cell lung, MCF-7 (breast cancer, and U251 (glioma. The MeOH phase showed activity (mean log GI50 0.54 higher than the hexane phase and EtOH extract (mean log GI50 1.13 and 1.19, resp.. F1 exhibited activity against NCI-H460 (nonsmall cell lung (GI50 1.2 μg/mL, which could be accounted for the presence of flavonoids and/or diterpenes. F4 showed moderate activity (mean log GI50 1.05, while F5 showed weak activity (mean log GI50 1.36. It is suggested that the antiproliferative activity of the crude EtOH extract and MeOH phase is accounted for a synergistic combination of flavonoids and diterpenes.

  5. Antiproliferative activity of flavonoids from Croton sphaerogynus Baill. (Euphorbiaceae).

    Science.gov (United States)

    dos Santos, Kátia Pereira; Motta, Lucimar B; Santos, Deborah Y A C; Salatino, Maria L F; Salatino, Antonio; Ferreira, Marcelo J Pena; Lago, João Henrique G; Ruiz, Ana Lúcia T G; de Carvalho, João E; Furlan, Cláudia M

    2015-01-01

    Croton sphaerogynus is a shrub from the Atlantic Rain Forest in southeastern Brazil. A lyophilized crude EtOH extract from leaves of C. sphaerogynus, obtained by maceration at room temperature (seven days), was suspended in methanol and partitioned with hexane. The purified MeOH phase was fractionated over Sephadex LH-20 yielding five fractions (F1-F5) containing flavonoids, as characterized by HPLC-DAD and HPLC-MS analyses. The antiproliferative activity of the crude EtOH extract, MeOH and hexane phases, and fractions F1-F5 was evaluated on in vitro cell lines NCI-H460 (nonsmall cell lung), MCF-7 (breast cancer), and U251 (glioma). The MeOH phase showed activity (mean log GI50 0.54) higher than the hexane phase and EtOH extract (mean log GI50 1.13 and 1.19, resp.). F1 exhibited activity against NCI-H460 (nonsmall cell lung) (GI50 1.2 μg/mL), which could be accounted for the presence of flavonoids and/or diterpenes. F4 showed moderate activity (mean log GI50 1.05), while F5 showed weak activity (mean log GI50 1.36). It is suggested that the antiproliferative activity of the crude EtOH extract and MeOH phase is accounted for a synergistic combination of flavonoids and diterpenes.

  6. Antiproliferative activity of flavonoids from Croton sphaerogynus Baill. (Euphorbiaceae).

    Science.gov (United States)

    dos Santos, Kátia Pereira; Motta, Lucimar B; Santos, Deborah Y A C; Salatino, Maria L F; Salatino, Antonio; Ferreira, Marcelo J Pena; Lago, João Henrique G; Ruiz, Ana Lúcia T G; de Carvalho, João E; Furlan, Cláudia M

    2015-01-01

    Croton sphaerogynus is a shrub from the Atlantic Rain Forest in southeastern Brazil. A lyophilized crude EtOH extract from leaves of C. sphaerogynus, obtained by maceration at room temperature (seven days), was suspended in methanol and partitioned with hexane. The purified MeOH phase was fractionated over Sephadex LH-20 yielding five fractions (F1-F5) containing flavonoids, as characterized by HPLC-DAD and HPLC-MS analyses. The antiproliferative activity of the crude EtOH extract, MeOH and hexane phases, and fractions F1-F5 was evaluated on in vitro cell lines NCI-H460 (nonsmall cell lung), MCF-7 (breast cancer), and U251 (glioma). The MeOH phase showed activity (mean log GI50 0.54) higher than the hexane phase and EtOH extract (mean log GI50 1.13 and 1.19, resp.). F1 exhibited activity against NCI-H460 (nonsmall cell lung) (GI50 1.2 μg/mL), which could be accounted for the presence of flavonoids and/or diterpenes. F4 showed moderate activity (mean log GI50 1.05), while F5 showed weak activity (mean log GI50 1.36). It is suggested that the antiproliferative activity of the crude EtOH extract and MeOH phase is accounted for a synergistic combination of flavonoids and diterpenes. PMID:26075219

  7. Evaluation of the Antiproliferative Activity of the Leaves from Arctium lappa by a Bioassay-Guided Fractionation

    OpenAIRE

    Celso Vataru Nakamura; João Carlos Palazzo de Mello; Tânia Ueda-Nakamura; Cláudio Roberto Novello; Ivânia Teresinha Albrecht Schuquel; Cássia Mônica Sakuragui; Heinrich Luftmann; Samara Requena Nocchi; Karine Zanoli; Rafael Eidi Yamamoto; Fabio Bahls Machado

    2012-01-01

    Arctium lappa L. (Asteraceae) is used in folk medicine around the World, and shows several kinds of biological activity, particularly in vitro antitumor activity in different cell lines. This study evaluated the antiproliferative activity of the crude extract, semipurified fractions, and isolated compounds from the leaves of A. lappa, through bioassay-guided testing in Caco-2 cells. The crude extract was obtained with a 50% hydroethanolic extract and then partitioned with hexane, ethyl acetat...

  8. The CK2 inhibitor quninalizarin enhances the anti-proliferative effect of icotinib on EGFR-TKIs-resistant cell lines and its underlying mechanisms%蛋白激酶2抑制剂增强盐酸埃克替尼对表皮生长因子受体-酪氨酸激酶抑制剂耐药细胞的增殖抑制作用及机制

    Institute of Scientific and Technical Information of China (English)

    周瑜; 伍钢; 孟睿; 张盛; 李珂; 李倩雯; 周方正; 李振宇; 马虹; 董晓荣; 刘莉

    2016-01-01

    [Abstr act] Objective To explore whether quninalizarin, an specific inhibitor of protein kinase CK2, could sensitize icotinib in EGFR-TKIs (epithelial growth factor receptor-tyrosine kinase inhibitor)-resistant cell lines and uncover the underlying mechanisms.Methods MTT assay was performed to evaluate the inhibitory effect of quninalizarin, icotinib or the combination of both on cell proliferation in several lung adenocarcinoma cell lines.Western blot assay was used to assess if combined inhibition of EGFR and protein kinase CK2 by icotinib and quninalizarin, exerts effect on the expression and phosphorylation of major proteins of EGFR signaling pathways.Results The IC50 of HCC827, H1650 , H1975 and A549 cells for icotinib were (8.07±2.00) μmol/L, (66.01±6.64) μmol/L, (265.60±9.47) μmol/L and( 87.88±6.8)μmol/L, respectively, indicating that HCC827 cells are sensitive to icotinib, and the H1650, H1975 and A549 cells are relatively resistant to icotinib.When treated with both quninalizarin and icotinib in the concentration of 50 μmol/L, the viability of H1650, H1975 and A549 cells was (40.64±3.73)%, (65.74± 3.27)% and (44.96±0.48)%, respectively, significantly lower than that of H1650 , H1975 and A549 cells treated with 50 μmol/L icotinib alone (55.05±1.22)%, (71.98±1.60)% and (61.74±6.18)%, respectively (P<0.01 for all).When treated with both 100 μmol/L quninalizarin and 100 μmol/L icotinib, the viability of H1650, H1975and A 549 ells were (23.35±0.81)%, (55.70±1.03)%, (33.42±1.33)%,respectively, significantly lower than the viability of H1650, H1975 and A549 cells treated with 100 μmol/L icotinib alone (40.57±2.65)%, (62.40±2.05)% and (44.97±8.20)%, respectively, (P<0.01 for all).The two-way ANOVA analysis showed that compared with the viability of EGFR-TKIs-resistant cells ( H1650, H1975, A549) treated with 50 μmol/L and 100 μmol/L icotinib alone, the viability of cells treated with icotinib and quinalizarin were significantly

  9. Sclareol, a plant diterpene, exhibits potent antiproliferative effects via the induction of apoptosis and mitochondrial membrane potential loss in osteosarcoma cancer cells.

    Science.gov (United States)

    Wang, Lin; He, Hong-Sheng; Yu, Hua-Long; Zeng, Yun; Han, Heng; He, Ning; Liu, Zhi-Gang; Wang, Zhi-Yong; Xu, Shou-Jia; Xiong, Min

    2015-06-01

    The objective of the current study was to evaluate the antiproliferative activity of sclareol against MG63 osteosarcoma cells. A 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay was used to evaluate the cell viability of cells following treatment with sclareol. The extent of cell death induced by sclareol was evaluated using a lactate dehydrogenase (LDH) assay. The effect of sclareol on cell cycle progression and mitochondrial membrane potential (ΛΨm) was evaluated with flow cytometry using the DNA‑binding fluorescent dyes propidium iodide and rhodamine‑123, respectively. Fluorescence microscopy was used to detect the morphological changes in the MG63 osteosarcoma cancer cells and the appearance of apoptotic bodies following sclareol treatment. The results revealed that sclareol induced dose‑ and time‑dependent growth inhibition of MG63 cancer cells with an IC50 value of 65.2 µM following a 12‑h incubation. Furthermore, sclareol induced a significant increase in the release of LDH from MG63 cell cultures, which was much more pronounced at higher doses. Fluorescence microscopy revealed that sclareol induced characteristic morphological features of apoptosis and the appearance of apoptotic bodies. Flow cytometry revealed that sclareol induced G1‑phase cell cycle arrest, which showed significant dose‑dependence. Additionally, sclareol induced a progressive and dose‑dependent reduction in the ΛΨm. In summary, sclareol inhibits the growth of osteosarcoma cancer cells via the induction of apoptosis, which is accompanied by G1‑phase cell cycle arrest and loss of ΛΨm.

  10. Synthesis and anti-proliferative activity of fluoro-substituted chalcones.

    Science.gov (United States)

    Burmaoglu, Serdar; Algul, Oztekin; Anıl, Derya Aktas; Gobek, Arzu; Duran, Gulay Gulbol; Ersan, Ronak Haj; Duran, Nizami

    2016-07-01

    A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729μM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound. PMID:27217001

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

    Energy Technology Data Exchange (ETDEWEB)

    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 [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Centro Pluridisciplinar de Pesquisas Quimicas, Biologicas e Agricolas (CPQBA)]. E-mail: foglioma@cpqba.unicamp.br; Tamashiro, Jorge Y. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Biologia

    2009-07-01

    Activity guided fractionation of Pterodon pubescens Benth. methylene chloride-soluble fraction afforded novel 6{alpha}-acetoxi 7{beta}-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{sub 50} (concentration that produces 50% growth inhibition), TGI (concentration that produces total growth inhibition or cytostatic effect) and LC{sub 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{sub 50} values, causing cytostatic effect (TGI value) at a concentration fifteen times less than positive control. Moreover comparison of 50% lethal concentration (LC{sub 50} value) with positive control (doxorubicin) suggested that compound 1 was less toxic. (author)

  12. Virus Discovery Using Tick Cell Lines

    Science.gov (United States)

    Bell-Sakyi, Lesley; Attoui, Houssam

    2016-01-01

    While ticks have been known to harbor and transmit pathogenic arboviruses for over 80 years, the application of high-throughput sequencing technologies has revealed that ticks also appear to harbor a diverse range of endogenous tick-only viruses belonging to many different families. Almost nothing is known about these viruses; indeed, it is unclear in most cases whether the identified viral sequences are derived from actual replication-competent viruses or from endogenous virus elements incorporated into the ticks’ genomes. Tick cell lines play an important role in virus discovery and isolation through the identification of novel viruses chronically infecting such cell lines and by acting as host cells to aid in determining whether or not an entire replication-competent, infective virus is present in a sample. Here, we review recent progress in tick-borne virus discovery and comment on the actual and potential applications for tick cell lines in this emerging research area. PMID:27679414

  13. Two new benzylisoquinoline alkaloids from Thalictrum foliolosum and their antioxidant and in vitro antiproliferative properties.

    Science.gov (United States)

    Li, Da-Hong; Guo, Jia; Bin, Wen; Zhao, Nan; Wang, Kai-Bo; Li, Jian-Yong; Li, Zhan-Lin; Hua, Hui-Ming

    2016-07-01

    Two novel rare chloro-containing benzylisoquinoline alkaloids, thalfoliolosumines A (1) and B (2), along with eight known isoquinoline alkaloids (3-10) were isolated from the whole plant of Thalictrum foliolosum. The structures of these compounds were elucidated by spectral analyses, including 1D and 2D NMR (COSY, HSQC, HMBC and NOESY) experiments. The antiproliferative effects of all the isolated compounds were evaluated by MTT method against MCF-7, PC-3, and U937 cells, and trypan blue method against HL-60 cells. New compounds 1 and 2 exhibited moderate in vitro antiproliferative activity against MCF-7, PC-3, and HL-60 cells, and good inhibitory effects against U937 cells with IC50 values of 7.50 and 6.97 μM, respectively. Compounds 7 and 10 showed the strongest in vitro antiproliferative with IC50 values of 0.93 and 1.69 μM against HL-60 cell line. The antioxidant properties were also measured, bisbenzyltetrahydroisoquinoline alkaloids 3-6 showed the strongest antioxidant activities in ABTS assay. PMID:26928743

  14. Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

    Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods: The microculture tetrazolium (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cytometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53and c-myc. Results: As2O3 inhibited the growth of RCC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0 μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells,but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion: As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

  15. Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

    Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods. The microculture tetrazolium (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cytometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53 and c-myc. Results: As2O3 inhibited the growth of ROC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells, but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion. As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

  16. Antioxidant, Antimicrobial and Antiproliferative Activities of Five Lichen Species

    Directory of Open Access Journals (Sweden)

    Snežana Marković

    2011-08-01

    Full Text Available The antioxidative, antimicrobial and antiproliferative potentials of the methanol extracts of the lichen species Parmelia sulcata, Flavoparmelia caperata, Evernia prunastri, Hypogymnia physodes and Cladonia foliacea were evaluated. The total phenolic content of the tested extracts varied from 78.12 to 141.59 mg of gallic acid equivalent (GA/g of extract and the total flavonoid content from 20.14 to 44.43 mg of rutin equivalent (Ru/g of extract. The antioxidant capacities of the lichen extracts were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH radicals scavenging. Hypogymnia physodes with the highest phenolic content showed the strongest DPPH radical scavenging effect. Further, the antimicrobial potential of the lichen extracts was determined by a microdilution method on 29 microorganisms, including 15 strains of bacteria, 10 species of filamentous fungi and 4 yeast species. A high antimicrobial activity of all the tested extracts was observed with more potent inhibitory effects on the growth of Gram (+ bacteria. The highest antimicrobial activity among lichens was demonstrated by Hypogymnia physodes and Cladonia foliacea. Finally, the antiproliferative activity of the lichen extracts was explored on the colon cancer adenocarcinoma cell line HCT-116 by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide viability assay and acridine orange/ethidium bromide staining. The methanol extracts of Hypogymnia physodes and Cladonia foliacea showed a better cytotoxic activity than the other extracts. All lichen species showed the ability to induce apoptosis of HCT-116 cells.

  17. C-Glycosidic Genistein Conjugates and Their Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Aleksandra Rusin

    2013-01-01

    Full Text Available This paper presents our attempt to investigate scopes and the limitations of olefin cross-metathesis (CM reaction in the synthesis of complex C-glycosides of genistein and evaluation of their antiproliferative activities. Novel genistein glycoconjugates were synthesized with the utility of CM reaction initiated by first and second generation of Grubbs catalysts. The relative reactivity of utilized olefins, based on categories proposed by Grubbs, was estimated. In vitro experiments in cancer cell lines showed that the selected derivatives (3a and 3f exhibited higher antiproliferative potential than the parent compound, genistein, and were able to block the cell cycle in the G2/M phase. The observed mechanism of action of C-glycosidic derivatives was similar to the activity of their O-glycosidic counterparts. These compounds were stable in culture medium. The obtained results show that our approach to genistein modification with application of cross-metathesis reaction allowed to obtain stable glycoconjugates with improved anticancer potential, compared to the parent isoflavone.

  18. Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Markus Hecht

    Full Text Available Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo.Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50 were calculated and compared to the blood levels in our patients and published data.The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5 μmol/l (= 9944 ng/ml, Nevirapine 239 μmol/l (= 63,786 ng/ml, Etravirine 89.0 μmol/l (= 38,740 ng/ml, Lersivirine 543 μmol/l (= 168,523 ng/ml, Delavirdine 171 μmol/l (= 78,072 ng/ml, Rilpivirine 24.4 μmol/l (= 8941 ng/ml. As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587 ng/ml (range 162-15,363 ng/ml, of Rilpivirine 144 ng/ml (range 0-572 ng/ml and of Nevirapine 4955 ng/ml (range 1856-8697 ng/ml. Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients.All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic

  19. BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine.

    Science.gov (United States)

    Gu, Yuexi; Helenius, Mikko; Väänänen, Kristiina; Bulanova, Daria; Saarela, Jani; Sokolenko, Anna; Martens, John; Imyanitov, Evgeny; Kuznetsov, Sergey

    2016-01-01

    Germ-line or somatic inactivation of BRCA1 is a defining feature for a portion of human breast cancers. Here we evaluated the anti-proliferative activity of 198 FDA-approved and experimental drugs against four BRCA1-mutant (HCC1937, MDA-MB-436, SUM1315MO2, and SUM149PT) and four BRCA1-wild-type (MDA-MB-231, SUM229PE, MCF10A, and MCF7) breast cancer cell lines. We found that all BRCA1-mutant cell lines were insensitive to inhibitors of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) Selumetinib and Pimasertib in contrast to BRCA1-wildtype control cell lines. However, unexpectedly, only two BRCA1-mutant cell lines, HCC1937 and MDA-MB-436, were hypersensitive to a nucleotide analogue 6-thioguanine (6-TG). SUM149PT cells readily formed radiation-induced RAD51-positive nuclear foci indicating a functional homologous recombination, which may explain their resistance to 6-TG. However, the reason underlying 6-TG resistance of SUM1315MO2 cells remains unclear. Our data reveal a remarkable heterogeneity among BRCA1-mutant cell lines and provide a reference for future studies. PMID:27313062

  20. Investigation of the selenium metabolism in cancer cell lines

    DEFF Research Database (Denmark)

    Lunøe, Kristoffer; Gabel-Jensen, Charlotte; Stürup, Stefan;

    2011-01-01

    The aim of this work was to compare different selenium species for their ability to induce cell death in different cancer cell lines, while investigating the underlying chemistry by speciation analysis. A prostate cancer cell line (PC-3), a colon cancer cell line (HT-29) and a leukaemia cell line...

  1. In Vitro Antioxidant, Antiproliferative, and Phytochemical Study in Different Extracts of Nyctanthes arbortristis Flowers

    Directory of Open Access Journals (Sweden)

    Manjulatha Khanapur

    2014-01-01

    Full Text Available Nyctanthes arbortristis L. (Oleaceae is widely used in the Indian system of traditional medicine and is reported to have various biological activities. The present study was intended to evaluate the antioxidant and antiproliferative activities of flower extracts of Nyctanthes arbortristis. The shade dried flowers were extracted with 95% ethanol under sonication and the antioxidant activities were investigated using in vitro assays along with the determination of phytochemical constituents (total polyphenol and total flavonoid. Arborside C and β-monogentiobioside ester of α-Crocetin were identified in crude active extracts through LCMS/MS analysis. The antiproliferative activity was carried out by MTT assay by employing different human cancer cell lines. The lowest IC50 value of 24.56 ± 6.63 μg/mL was observed against Colo 205 cell line. The extract exhibited significant antioxidant and antiproliferative properties and the observed biological activities in this study provide scientific validation of ethnomedicinal use of this plant.

  2. In Vitro Antioxidant and Antiproliferative Activities of Methanolic Plant Part Extracts of Theobroma cacao

    Directory of Open Access Journals (Sweden)

    Zainal Baharum

    2014-11-01

    Full Text Available The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH, thiobarbituric acid-reactive substances (TBARS, and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50 was 358.3 ± 7.0 µg/mL and total phenolic content was 22.0 ± 1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4% ± 1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50 = 41.4 ± 3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.

  3. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    Science.gov (United States)

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.

  4. NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins

    Directory of Open Access Journals (Sweden)

    Dahong Li

    2016-09-01

    Full Text Available A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO donor hybrids (10a–i were designed and synthesized from commercially available oridonin (1. These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC50 of 0.81 μM and could also release 33.7 μmol/L NO at the time point of 60 min. Compounds 10a–i also showed cytotoxic selectivity between tumor and normal liver cells with IC50 ranging from 22.1 to 33.9 μM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations.

  5. Antiproliferative and pro-apoptotic effects of three fungal exocellular β-glucans in MCF-7 breast cancer cells is mediated by oxidative stress, AMP-activated protein kinase (AMPK) and the Forkhead transcription factor, FOXO3a.

    Science.gov (United States)

    Queiroz, Eveline A I F; Fortes, Zuleica B; da Cunha, Mário A A; Barbosa, Aneli M; Khaper, Neelam; Dekker, Robert F H

    2015-10-01

    Fungal β-d-glucans of the (1→3)-type are known to exhibit direct antitumor effects, and can also indirectly decrease tumor proliferation through immunomodulatory responses. The underlying molecular mechanisms involved in decreasing tumor formation, however, are not well understood. In this study, we examined the antiproliferative role and mechanism of action of three different fungal exocellular β-glucans in MCF-7 breast cancer cells. The β-glucans were obtained from Botryosphaeria rhodina MAMB-05 [two botryosphaerans; (1→3)(1→6)-β-d-glucan; one produced on glucose, the other on fructose] and Lasiodiplodia theobromae MMPI [lasiodiplodan; (1→6)-β-d-glucan, produced on glucose]. Using the cell proliferation-MTT assay, we showed that the β-glucans exhibited a time- and concentration-dependent antiproliferative activity (IC50, 100μg/ml). Markers of cell cycle, apoptosis, necrosis and oxidative stress were analyzed using flow cytometry, RT-PCR and Western blotting. Exposure to β-glucans increased apoptosis, necrosis, oxidative stress, mRNA expression of p53, p27 and Bax; the activity of AMP-activated protein-kinase, Forkhead transcription factor FOXO3a, Bax and caspase-3; and decreased the activity of p70S6K in MCF-7 cells. In the presence of hydrogen peroxide, the fungal β-glucans increased oxidative stress, which was associated with reduced cell viability. We showed that these β-glucans exhibited an antiproliferative effect that was associated with apoptosis, necrosis and oxidative stress. This study demonstrated for the first time that the apoptosis induced by β-glucans was mediated by AMP-activated protein-kinase and Forkhead transcription factor, FOXO3a. Our findings provide novel mechanistic insights into their antiproliferative roles, and compelling evidence that these β-glucans possess a broad range of biomodulatory properties that may prove useful in cancer treatment. PMID:26255117

  6. Forced Trefoil Factor Family Peptide 3 (TFF3) Expression Reduces Growth, Viability, and Tumorigenicity of Human Retinoblastoma Cell Lines.

    Science.gov (United States)

    Große-Kreul, Jan; Busch, Maike; Winter, Claudia; Pikos, Stefanie; Stephan, Harald; Dünker, Nicole

    2016-01-01

    Trefoil factor family (TFF) peptides have been shown to effect cell proliferation, apoptosis, migration and invasion of normal cells and various cancer cell lines. In the literature TFF peptides are controversially discussed as tumor suppressors and potential tumor progression factors. In the study presented, we investigated the effect of TFF3 overexpression on growth, viability, migration and tumorigenicity of the human retinoblastoma cell lines Y-79, WERI-Rb1, RBL-13 and RBL-15. As revealed by WST-1 and TUNEL assays as well as DAPI and BrdU cell counts, recombinant human TFF3 significantly lowers retinoblastoma cell viability and increases apoptosis levels. Transient TFF3 overexpression likewise significantly increases RB cell apoptosis. Stable, lentiviral TFF3 overexpression lowers retinoblastoma cell viability, proliferation and growth and significantly increases cell death in retinoblastoma cells. Blockage experiments using a broad-spectrum caspase inhibitor and capase-3 immunocytochemistry revealed the involvement of caspases in general and of caspase-3 in particular in TFF3 induced apoptosis in retinoblastoma cell lines. Soft agarose and in ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF3 overexpression influences anchorage independent growth and significantly decreases the size of tumors forming from retinoblastoma cells. Our study demonstrates that forced TFF3 expression exerts a significant pro-apoptotic, anti-proliferative, and tumor suppressive effect in retinoblastoma cells, setting a starting point for new additive chemotherapeutic approaches in the treatment of retinoblastoma.

  7. Forced Trefoil Factor Family Peptide 3 (TFF3) Expression Reduces Growth, Viability, and Tumorigenicity of Human Retinoblastoma Cell Lines

    Science.gov (United States)

    Winter, Claudia; Pikos, Stefanie; Stephan, Harald; Dünker, Nicole

    2016-01-01

    Trefoil factor family (TFF) peptides have been shown to effect cell proliferation, apoptosis, migration and invasion of normal cells and various cancer cell lines. In the literature TFF peptides are controversially discussed as tumor suppressors and potential tumor progression factors. In the study presented, we investigated the effect of TFF3 overexpression on growth, viability, migration and tumorigenicity of the human retinoblastoma cell lines Y-79, WERI-Rb1, RBL-13 and RBL-15. As revealed by WST-1 and TUNEL assays as well as DAPI and BrdU cell counts, recombinant human TFF3 significantly lowers retinoblastoma cell viability and increases apoptosis levels. Transient TFF3 overexpression likewise significantly increases RB cell apoptosis. Stable, lentiviral TFF3 overexpression lowers retinoblastoma cell viability, proliferation and growth and significantly increases cell death in retinoblastoma cells. Blockage experiments using a broad-spectrum caspase inhibitor and capase-3 immunocytochemistry revealed the involvement of caspases in general and of caspase-3 in particular in TFF3 induced apoptosis in retinoblastoma cell lines. Soft agarose and in ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF3 overexpression influences anchorage independent growth and significantly decreases the size of tumors forming from retinoblastoma cells. Our study demonstrates that forced TFF3 expression exerts a significant pro-apoptotic, anti-proliferative, and tumor suppressive effect in retinoblastoma cells, setting a starting point for new additive chemotherapeutic approaches in the treatment of retinoblastoma. PMID:27626280

  8. Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis By-Products

    Directory of Open Access Journals (Sweden)

    Marie-Elise Carbonneau

    2013-03-01

    Full Text Available Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides. The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated. Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction. At a protein concentration of 44 µg/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At the low protein concentration of only 11 µg/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids. The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods.

  9. Comprehensive Proteomic Study of the Antiproliferative Activity of a Polyphenol-Enriched Rosemary Extract on Colon Cancer Cells Using Nanoliquid Chromatography-Orbitrap MS/MS.

    Science.gov (United States)

    Valdés, Alberto; Artemenko, Konstantin A; Bergquist, Jonas; García-Cañas, Virginia; Cifuentes, Alejandro

    2016-06-01

    In this work, a proteomics strategy based on nanoliquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) using an Orbitrap high-resolution mass spectrometer together with stable isotope dimethyl labeling (DML) is applied to quantitatively examine relative changes in the protein fraction of HT-29 human colon cancer cells treated with different concentrations of a polyphenol-enriched rosemary extract over the time. The major objective of this study was to gain insights into the antiproliferative mechanisms induced by rosemary polyphenols. Using this methodology, 1909 and 698 proteins were identified and quantified in cell extracts. The polyphenol-enriched rosemary extract treatment changed the expression of several proteins in a time- and concentration-dependent manner. Most of the altered proteins are implicated in the activation of Nrf2 transcription factor and the unfolded protein response. In conclusion, rosemary polyphenols induced proteomic changes that were related to the attenuation of aggresome formation and activation of autophagy to alleviate cellular stress. PMID:27103343

  10. 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.

  11. Synergistic effect of combining paeonol and cisplatin on apoptotic induction of human hepatoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Shu-ping XU; Guo-ping SUN; Yu-xian SHEN; Wan-ten PENG; Hua WANG; Wei WE

    2007-01-01

    Aim: To investigate whether paeonol (Pae) has synergistic effects with cisplatin (CDDP) on the growth-inhibition and apoptosis-induction of human hepatoma cell lines HepG2 and SMMC-7721.Methods: The cytotoxic effect of drugs was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The coefficient of drug interaction was used to analyze the nature of drug interactions. Morphological changes were observed by acridine orange fluo-rescence staining. Cell cycle and the apoptosis rate were detected by flow cytometry. Bcl-2 and Bax expression were assayed by immunohistochemical staining.Results: Pae or CDDP had antiproliferative effect on the 2 cell lines in a dose-dependent manner, with different sensitivities to drugs. More interestingly, a synergistic inhibitory effect on the viability of the 2 cell lines was observed after treatment with a combination of Pae (15.63, 31.25, and 62.5 mg/L) with various concentrations of CDDP. Further study showed typical mor-phological changes of apoptosis if the cells were exposed to the two agents for 24 h. The apoptotic rate of the cells with combination treatment was signifi-candy higher than that of cells treated with Pae or CDDP alone. The expression of Bcl-2 decreased and that of Bax increased in the treated groups, especially in the combination group, with the ratio of Bcl-2/Bax decreasing correspondingly.Additionally, a combination of Pae with CDDP resulted in a stronger S phase arrest, compared with Pae or CDDP alone.Conclusion: Pae, in combination with CDDP, had a significantly synergistic growth-inhibitory and apoptosis-in-ducing effect on the 2 human hepatoma cell lines, which may be useful in hepatoma treatment.

  12. Isolation, Identification and Antiproliferative Activity of Triterpenes from the Genus Monotheca A. DC.

    Directory of Open Access Journals (Sweden)

    Shabnam Javed

    2016-05-01

    Full Text Available The Monotheca A. DC. is a monotypic genus of the family Sapotaceae, which is widely distributed in Afghanistan, Djbouti, Northern Somalia, Oman, Pakistan and Southern Ethiopia. North-west Pakistan is the main region where Monotheca buxifolia (Falc. A. DC., the only species of this genus, locally known as “Gurgura”, grows abundantly. It is an evergreen, fruit-producing medicinal tree. Bioassay-guided fractionation of the aerial parts of M. buxifolia afforded lupeol (1, lupeol acetate (2, betulin (3, oleanolic acid (4 andβ-amyrin (5 from the n-hexane and the chloroform fractions. This is the first report on the isolation, and identification of triterpenes (1-5 as the major compounds in the active fractions with antiproliferative property, and also on the antiproliferative activity of M. buxifolia extract and fractions against the human lung cancer cell line NCI-H460 in vitro.

  13. Antiproliferative Compounds from Ocotea macrocarpa from the Madagascar Dry Forest1

    Science.gov (United States)

    Liu, Yixi; Cheng, Emily; Rakotondraibe, L. Harinantenaina; Brodie, Peggy J.; Applequist, Wendy; Randrianaivo, Richard; Rakotondrafara, Andriamalala; Ratsimbason, Michel; Rasamison, Vincent E.; Kingston, David G. I.

    2015-01-01

    Bioassay-directed fractionation of an antiproliferative ethanol extract of the roots of Ocotea macrocarpa (Lauraceae) afforded the new butanolide macrocarpolide A (1), and the two new secobutanolides macrocarpolides B (2) and C (3), together with the known butanolides linderanolide B (4) and isolinderanolide (5). The structure elucidation of all compounds was carried out based on NMR and mass spectroscopic data analyses. The absolute configurations of all compounds isolated were determined by comparison of their optical rotation values with those found in literature. Compounds 1–5 showed good antiproliferative activities against the A2780 ovarian cell line, with IC50 values of 2.57 ± 0.12 (1), 1.98 ± 0.23 (2), 1.67 ± 0.05 (3), 2.43 ± 0.41 (4), and 1.65 ± 0.44 µM (5), respectively. PMID:26034338

  14. Formulation of Anti-miR-21 and 4-Hydroxytamoxifen Co-loaded Biodegradable Polymer Nanoparticles and Their Antiproliferative Effect on Breast Cancer Cells.

    Science.gov (United States)

    Devulapally, Rammohan; Sekar, Thillai V; Paulmurugan, Ramasamy

    2015-06-01

    Breast cancer is the second leading cause of cancer-related death in women. The majority of breast tumors are estrogen receptor-positive (ER+) and hormone-dependent. Neoadjuvant anti-estrogen therapy has been widely employed to reduce tumor mass prior to surgery. Tamoxifen is a broadly used anti-estrogen for early and advanced ER+ breast cancers in women and the most common hormone treatment for male breast cancer. 4-Hydroxytamoxifen (4-OHT) is an active metabolite of tamoxifen that functions as an estrogen receptor antagonist and displays higher affinity for estrogen receptors than that of tamoxifen and its other metabolites. MicroRNA-21 (miR-21) is a small noncoding RNA of 23 nucleotides that regulates several apoptotic and tumor suppressor genes and contributes to chemoresistance in numerous cancers, including breast cancer. The present study investigated the therapeutic potential of 4-OHT and anti-miR-21 coadministration in an attempt to combat tamoxifen resistance, a common problem often encountered in anti-estrogen therapy. A biodegradable poly(d,l-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG-COOH) copolymer was utilized as a carrier to codeliver 4-OHT and anti-miR-21 to ER+ breast cancer cells. 4-OHT and anti-miR-21 co-loaded PLGA-b-PEG nanoparticles (NPs) were developed using emulsion-diffusion evaporation (EDE) and water-in-oil-in-water (w/o/w) double emulsion methods. The EDE method was found to be best method for 4-OHT loading, and the w/o/w method proved to be more effective for coloading NPs with anti-miR-21 and 4-OHT. The optimal NPs, which were prepared using the double emulsion method, were evaluated for their antiproliferative and apoptotic effects against MCF7, ZR-75-1, and BT-474 human breast cancer cells as well as against 4T1 mouse mammary carcinoma cells. We demonstrated that PLGA-b-PEG NP encapsulation significantly extended 4-OHT's stability and biological activity compared to that of free 4-OHT. MTT assays indicated that

  15. Apoptotic induction by pinobanksin and some of its ester derivatives from Sonoran propolis in a B-cell lymphoma cell line.

    Science.gov (United States)

    Alday, Efrain; Valencia, Dora; Carreño, Ana Laura; Picerno, Patrizia; Piccinelli, Anna Lisa; Rastrelli, Luca; Robles-Zepeda, Ramon; Hernandez, Javier; Velazquez, Carlos

    2015-12-01

    Propolis is a resinous substance produced by honeybees (Apis mellifera) from the selective collection of exudates and bud secretions from several plants. In previous works, we reported the antiproliferative activity of Sonoran propolis (SP) on cancer cells; in addition we suggested the induction of apoptosis after treatment with SP due to the presence of morphological changes and a characteristic DNA fragmentation pattern. Herein, in this study we demonstrated that the antiproliferative effect of SP is induced through apoptosis in a B-cell lymphoma cancer cell line, M12.C3.F6, by an annexin V-FITC/Propidium iodide double labeling. This apoptotic effect of SP resulted to be mediated by modulations in the loss of mitochondrial membrane potential (ΔΨm) and through activation of caspases signaling pathway (3, 8 and 9). Afterward, in order to characterize the chemical constituents of SP that induce apoptosis in cancer cells, an HPLC-PDA-ESI-MS/MS method followed by a preparative isolation procedure and NMR spectroscopy analysis have been used. Eighteen flavonoids, commonly described in propolis from temperate regions, were characterized. Chrysin, pinocembrin, pinobanksin and its ester derivatives are the main constituents of SP and some of them have never been reported in SP. In addition, two esters of pinobanksin (8 and 13) are described by first time in propolis samples in general. The antiproliferative activity on M12.C3.F6 cells through apoptosis induction was exhibited by pinobanksin (4), pinobanksin-3-O-propanoate (14), pinobanksin-3-O-butyrate (16), pinobanksin-3-O-pentanoate (17), and the already reported galangin (11), chrysin (9) and CAPE. To our knowledge this is the first report of bioactivity of pinobanksin and some of its ester derivatives as apoptosis inducers. Further studies are needed to advance in the understanding of the molecular basis of apoptosis induction by SP and its constituents, as well as the structure-activity relationship of them.

  16. Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid

    Directory of Open Access Journals (Sweden)

    Mariano Walter Pertino

    2014-02-01

    Full Text Available Dehydroabietic acid (DHA is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid, and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol, four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells. Better antiproliferative effect was found for compound 5, with an IC50 of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC50 of etoposide, was 1.83 µM.

  17. Phytochemical screening and antioxidant, antimitotic, and antiproliferative activities of Trichodesma indicum shoot

    Directory of Open Access Journals (Sweden)

    Shweta S Saboo

    2014-01-01

    Full Text Available Background: Traditionally Trichodesma indicum has been used for its therapeutic effect in folk medicine that include anti-inflammatory, analgesic and anticancer properties. In this work, we validate the anticancer potential of the plant. Aims: To screen the shoot extracts T. indicum for their antimitotic and antiproliferative activities. Materials and Methods: The dried aerial parts of T. indicum were successively extracted with petroleum ether, successive chloroform extract (SCH, successive ethanol extract (SEE and water. The plant extracts were subjected to study of in vitro antioxidant activity using 2,2′- diphenyl-1-picrylhydrazyl, 2,2′- azino-bis(3-ethylbenzothiazoline-6-sulphonic acid radical inhibition systems. The extracts were also tested for their in vitro antimitotic activity in Allium cepa root and antiproliferative activity using the yeast model and five human cell lines (MCF-7, HOP-62, MOLT-4, HCT-15 and PRO. Result and Conclusion: The mitotic index for SCH and SEE was found to be 12.01 ± 1.34 and 12.99 ± 0.25 mg/mL, respectively. The IC 50 value in the antiproliferative assay was found to be 30.14-35.36 mg/mL for SCH and SEE respectively. Both SCH and SEE extracts showed significant antimitotic and antiproliferative activity when compared to the standard methothreaxate, vincreastine and adriamycin. Among the extracts, SEE showed strong inhibition against MCF-7 and MOLT-4 cell lines at concentration <30 μg/mL. Phytochemical analysis of extracts indicated the presence of β-sitosterol, gallic acid and catechin. Based on these results, it is concluded that T. indicum may be a good candidate for the treatment of a variety of cancer. Thus, its traditional use is validated.

  18. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Felthaus, O. [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany); Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Ettl, T.; Gosau, M.; Driemel, O. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Brockhoff, G. [Department of Gynecology and Obstetrics, University of Regensburg (Germany); Reck, A. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Zeitler, K. [Institute of Pathology, University of Regensburg (Germany); Hautmann, M. [Department of Radiotherapy, University of Regensburg (Germany); Reichert, T.E. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Schmalz, G. [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany); Morsczeck, C., E-mail: christian.morsczeck@klinik.uni-regensburg.de [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany)

    2011-04-01

    Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.

  19. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    International Nuclear Information System (INIS)

    Research highlights: → Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). → Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. → Monoclonal cell lines showed reduced sensitivity for Paclitaxel. → In situ CD133+ cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. → CD133+ and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133+ cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.

  20. Bufalin induces apoptosis in human osteosarcoma U-20S and U-20S methotrexate3OO-resistant cell lines

    Institute of Scientific and Technical Information of China (English)

    Jun-qiang YIN; Fo-bao LI; Jing-nan SHEN; Wei-wei SU; Jin WANG; Gang HUANG; Song JIN; Qian-chen GUO; Chang-ye ZOU; Hao-miao LI

    2007-01-01

    Aim: To investigate the antiproliferative activity and apoptosis-inducing effects of bufalin on human osteosarcoma cell lines. Methods: U-2OS and U-2OS meth-otrexate (MTX) 300-resistant cell lines were treated with bufalin. Cell viability was assessed using the MTT assay. Cell-cycle status, apoptosis-inducing effects,and the expression of apoptosis-related proteins were evaluated by flow cytometry,fluorescent staining, DNA fragmentation assays, and Western blotting. The ef-fect of bufalin on dihydrofolate reductase (DHFR) expression was studied by RT-PCR and Western blotting. Results: Bufalin inhibited cell growth in both U-2OS and U-2OS MTX300 cells. The induction of G2/M cell-cycle arrest was also seen in the cells treated with bufalin. The induction of apoptosis by bufalin was con-firmed by increased expression of the tumor suppressor protein p53 and the in-creased ratio of the Bax/Bcl-2 proteins. Bufalin induced apoptosis to the same extent in both cell lines without regard to DHFR levels in the cells. Conclusion:Bufalin inhibited the growth of and induced apoptosis in both MTX-sensitive and MTX-resistant human osteosarcoma U-2OS cells. The apoptosis-inducing effect of bufalin was not influenced by the presence of high levels of the DHFR protein.

  1. Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines.

    Science.gov (United States)

    Gallardo, Marcela; Calaf, Gloria M

    2016-09-01

    Curcumin (diferuloyl methane) is an antioxidant that exerts antiproliferative and apoptotic effects and has anti-invasive and anti-metastatic properties. Evidence strongly implicates that epithelial-mesenchymal transition (EMT) is involved in malignant progression affecting genes such as Slug, AXL and Twist1. These genes are abnormally expressed in many tumors and favor metastasis. The purpose of this study was to determine the potential effect of curcumin on EMT, migration and invasion. Triple-positive and triple-negative breast cancer cell lines for estrogen receptor (ER), progesterone receptor (PgR) and HER/neu were used: i) MCF-10F, a normal immortalized breast epithelial cell line (negative), ii) Tumor2, a malignant and tumorigenic cell line (positive) derived from Alpha5 cell line injected into the immunologically depressed mice and transformed by 60/60 cGy doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation and estrogen, and iii) a commercially available MDA-MB‑231 (negative). The effect of curcumin (30 µM for 48 h) was evaluated on expression of EMT-related genes by RT-qPCR. Results showed that curcumin decreased E-cadherin, N-cadherin, β-catenin, Slug, AXL, Twist1, Vimentin and Fibronectin protein expression, independently of the positivity of the markers in the cell lines. Curcumin also decreased migration and invasive capabilities in comparison to their own controls. It can be concluded that curcumin influenced biochemical changes associated with EMT-related genes that seems to promote such transition and are at the core of several signaling pathways that mediate the transition. Thus, it can be suggested that curcumin is able to prevent or delay cancer progression through the interruption of this process.

  2. Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines.

    Science.gov (United States)

    Gallardo, Marcela; Calaf, Gloria M

    2016-09-01

    Curcumin (diferuloyl methane) is an antioxidant that exerts antiproliferative and apoptotic effects and has anti-invasive and anti-metastatic properties. Evidence strongly implicates that epithelial-mesenchymal transition (EMT) is involved in malignant progression affecting genes such as Slug, AXL and Twist1. These genes are abnormally expressed in many tumors and favor metastasis. The purpose of this study was to determine the potential effect of curcumin on EMT, migration and invasion. Triple-positive and triple-negative breast cancer cell lines for estrogen receptor (ER), progesterone receptor (PgR) and HER/neu were used: i) MCF-10F, a normal immortalized breast epithelial cell line (negative), ii) Tumor2, a malignant and tumorigenic cell line (positive) derived from Alpha5 cell line injected into the immunologically depressed mice and transformed by 60/60 cGy doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation and estrogen, and iii) a commercially available MDA-MB‑231 (negative). The effect of curcumin (30 µM for 48 h) was evaluated on expression of EMT-related genes by RT-qPCR. Results showed that curcumin decreased E-cadherin, N-cadherin, β-catenin, Slug, AXL, Twist1, Vimentin and Fibronectin protein expression, independently of the positivity of the markers in the cell lines. Curcumin also decreased migration and invasive capabilities in comparison to their own controls. It can be concluded that curcumin influenced biochemical changes associated with EMT-related genes that seems to promote such transition and are at the core of several signaling pathways that mediate the transition. Thus, it can be suggested that curcumin is able to prevent or delay cancer progression through the interruption of this process. PMID:27573203

  3. Fenofibrate down-regulates the expressions of androgen receptor (AR) and AR target genes and induces oxidative stress in the prostate cancer cell line LNCaP

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hu; Zhu, Chen; Qin, Chao [State Key Laboratory of Reproductive Medicine, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Tao, Tao [Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Li, Jie; Cheng, Gong; Li, Pu; Cao, Qiang; Meng, Xiaoxin; Ju, Xiaobing; Shao, Pengfei; Hua, Lixin [State Key Laboratory of Reproductive Medicine, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Gu, Min, E-mail: medzhao1980@163.com [State Key Laboratory of Reproductive Medicine, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Yin, Changjun, E-mail: drcjyin@gmail.com [State Key Laboratory of Reproductive Medicine, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2013-03-08

    Highlights: ► Fenofibrate induces cell cycle arrest in G1 phase and apoptosis in LNCaP cells. ► Fenofibrate reduces the expressions of androgen receptor in LNCaP cells. ► Fenofibrate induces oxidative stress in the prostate cancer cell line LNCaP. -- Abstract: Fenofibrate, a peroxisome proliferator-androgen receptor-alpha agonist, is widely used in treating different forms of hyperlipidemia and hypercholesterolemia. Recent reports have indicated that fenofibrate exerts anti-proliferative and pro-apoptotic properties. This study aims to investigate the effects of fenofibrate on the prostate cancer (PCa) cell line LNCaP. The effects of fenofibrate on LNCaP cells were evaluated by flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assays, Western blot analysis, and dual-luciferase reporter assay. Fenofibrate induces cell cycle arrest in G1 phase and apoptosis in LNCaP cells, reduces the expressions of androgen receptor (AR) and AR target genes (prostate-specific antigen and TMPRSS2), and inhibits Akt phosphorylation. Fenofibrate can induce the accumulation of intracellular reactive oxygen species and malondialdehyde, and decrease the activities of total anti-oxidant and superoxide dismutase in LNCaP cells. Fenofibrate exerts an anti-proliferative property by inhibiting the expression of AR and induces apoptosis by causing oxidative stress. Therefore, our data suggest fenofibrate may have beneficial effects in fenofibrate users by preventing prostate cancer growth through inhibition of androgen activation and expression.

  4. Fenofibrate down-regulates the expressions of androgen receptor (AR) and AR target genes and induces oxidative stress in the prostate cancer cell line LNCaP

    International Nuclear Information System (INIS)

    Highlights: ► Fenofibrate induces cell cycle arrest in G1 phase and apoptosis in LNCaP cells. ► Fenofibrate reduces the expressions of androgen receptor in LNCaP cells. ► Fenofibrate induces oxidative stress in the prostate cancer cell line LNCaP. -- Abstract: Fenofibrate, a peroxisome proliferator-androgen receptor-alpha agonist, is widely used in treating different forms of hyperlipidemia and hypercholesterolemia. Recent reports have indicated that fenofibrate exerts anti-proliferative and pro-apoptotic properties. This study aims to investigate the effects of fenofibrate on the prostate cancer (PCa) cell line LNCaP. The effects of fenofibrate on LNCaP cells were evaluated by flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assays, Western blot analysis, and dual-luciferase reporter assay. Fenofibrate induces cell cycle arrest in G1 phase and apoptosis in LNCaP cells, reduces the expressions of androgen receptor (AR) and AR target genes (prostate-specific antigen and TMPRSS2), and inhibits Akt phosphorylation. Fenofibrate can induce the accumulation of intracellular reactive oxygen species and malondialdehyde, and decrease the activities of total anti-oxidant and superoxide dismutase in LNCaP cells. Fenofibrate exerts an anti-proliferative property by inhibiting the expression of AR and induces apoptosis by causing oxidative stress. Therefore, our data suggest fenofibrate may have beneficial effects in fenofibrate users by preventing prostate cancer growth through inhibition of androgen activation and expression

  5. Antioxidant and Antiproliferative Activities of Heated Sterilized Pepsin Hydrolysate Derived from Half-Fin Anchovy (Setipinna taty

    Directory of Open Access Journals (Sweden)

    Dongfeng Wang

    2011-06-01

    Full Text Available In this paper we studied the antioxidant and antiproliferative activities of the heated pepsin hydrolysate from a marine fish half-fin anchovy (HAHp-H. Furthermore, we compared the chemical profiles including the amino acid composition, the browning intensity, the IR and UV-visible spectra, and the molecular weight distribution between the half-fin anchovy pepsin hydrolysate (HAHp and HAHp-H. Results showed that heat sterilization on HAHp improved the 1,1-diphenyl-2-picryl-hydrazil (DPPH radical-scavenging activity and reducing power. In addition, the antiproliferative activities were all increased for HAHp-H on DU-145 human prostate cancer cell line, 1299 human lung cancer cell line and 109 human esophagus cancer cell line. The contents of free amino acid and reducing sugar of HAHp-H were decreased (P < 0.05. However, hydrophobic amino acid residues and the browning intensity of HAHp-H were increased. FT-IR spectroscopy indicated that amide I and amide III bands of HAHp-H were slightly modified, whereas band intensity of amide II was reduced dramatically. Thermal sterilization resulted in the increased fractions of HAHp-H with molecular weight of 3000–5000 Da and below 500 Da. The enhanced antioxidant and antiproliferative activities of HAHp-H might be attributed to the Maillard reaction.

  6. Antiproliferative Effects of New Dimeric Ellagitannin from Cornus alba in Prostate Cancer Cells Including Apoptosis-Related S-Phase Arrest.

    Science.gov (United States)

    Park, Kwan Hee; Yin, Jun; Yoon, Ki Hoon; Hwang, Yoon Jeong; Lee, Min Won

    2016-01-01

    Activity-guided isolation of 80% acetone extract of Cornus alba, which is traditionally used as an anti-inflammatory, hemostatic and diuretic in Korea, yielded one novel compound, tentatively designated cornusiin H (13), together with 12 known compounds. The known compounds included four flavonoids (catechin (1), quercetin-3-O-β-D-glucuronide (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4)) and eight hydrolysable tannins (gallic acid (5), 2,6-di-O-galloyl-hamamelofuranoside (6), 2-galloyl-4-caffeoyl-L-threonic acid (7) 2,3-di-O-galloyl-4-caffeoyl-L-threonic acid (8), 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranoside (9), cornusiin B (10), cornusiin A (11) and camptothin B (12)). All compounds exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity. Especially, the radical scavenging activities of 6 and 9-13 were higher than that of vitamin C. Compounds 9, 11, 12 and 13 inhibited the production of nitric oxide (NO) in lipopolysaccharide-stimulated RAW264.7 cells to the same degree as N(G)-Monomethyl-L-arginine (L-NMMA). When the antiproliferative effects of the isolated compounds were assessed in prostate cancer cells, the dimeric ellagitannins (11-13) selectively inhibited LNCaP hormone-dependent prostate cancer cells. Flow cytometry analysis indicated that the dimeric ellagitannins induced apoptosis and S-phase arrest. These results suggest that dimeric ellagitannins from Cornus alba can be developed as functional materials or herbal medicines for prostate tumors such as benign prostate hyperplasia and early-stage prostate cancer. PMID:26805810

  7. Antiproliferative Effects of New Dimeric Ellagitannin from Cornus alba in Prostate Cancer Cells Including Apoptosis-Related S-Phase Arrest

    Directory of Open Access Journals (Sweden)

    Kwan Hee Park

    2016-01-01

    Full Text Available Activity-guided isolation of 80% acetone extract of Cornus alba, which is traditionally used as an anti-inflammatory, hemostatic and diuretic in Korea, yielded one novel compound, tentatively designated cornusiin H (13, together with 12 known compounds. The known compounds included four flavonoids (catechin (1, quercetin-3-O-β-d-glucuronide (2, quercetin-3-O-β-d-glucopyranoside (3, kaempferol-3-O-β-d-glucopyranoside (4 and eight hydrolysable tannins (gallic acid (5, 2,6-di-O-galloyl-hamamelofuranoside (6, 2-galloyl-4-caffeoyl-l-threonic acid (7 2,3-di-O-galloyl-4-caffeoyl-l-threonic acid (8, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (9, cornusiin B (10, cornusiin A (11 and camptothin B (12. All compounds exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH-free radical scavenging activity. Especially, the radical scavenging activities of 6 and 9–13 were higher than that of vitamin C. Compounds 9, 11, 12 and 13 inhibited the production of nitric oxide (NO in lipopolysaccharide-stimulated RAW264.7 cells to the same degree as NG-Monomethyl-l-arginine (l-NMMA. When the antiproliferative effects of the isolated compounds were assessed in prostate cancer cells, the dimeric ellagitannins (11–13 selectively inhibited LNCaP hormone-dependent prostate cancer cells. Flow cytometry analysis indicated that the dimeric ellagitannins induced apoptosis and S-phase arrest. These results suggest that dimeric ellagitannins from Cornus alba can be developed as functional materials or herbal medicines for prostate tumors such as benign prostate hyperplasia and early-stage prostate cancer.

  8. Antioxidant, Cytotoxic, and Antiproliferative Activities and Total Polyphenol Contents of the Extracts of Geissospermum reticulatum Bark

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    Joanna J. Sajkowska-Kozielewicz

    2016-01-01

    Full Text Available Geissospermum species are medically important plants due to their health-promoting effects. The objective of this study was to determine the antioxidant ability and antiproliferative and cytotoxic effects of infusions, tinctures, and ethanolic extracts of Geissospermum reticulatum barks in relation to the contents of total phenolics and flavonoids. Seven samples of barks were collected in various regions of Peruvian Amazonia. We found that the amount of total phenolics in the studied products varied from 212.40 ± 0.69 to 1253.92 ± 11.20 mg GAE/kg. In our study there is a correlation (R2=0.7947 between the results of antioxidants assays: FRAP and ORAC for tinctures, infusions, and ethanolic extracts of G. reticulatum barks. We have also observed antiproliferative activities of the ethanolic extracts on normal T-cells. These extracts have caused death on malignant cell lines (THP-1 and HL-60 and this data correlates well with their antioxidant capacity measured by ORAC method. Interestingly, the highest concentration of the ethanolic extract was not toxic in the zebrafish embryo developmental assay. Our results indicate that G. reticulatum is rich in antioxidants and have cytotoxic and antiproliferative properties. The data suggests potential immunosuppressive role of the extracts. This is the first study presenting the results of chemical and biological analysis of multiple preparations from G. reticulatum.

  9. Antioxidant, Cytotoxic, and Antiproliferative Activities and Total Polyphenol Contents of the Extracts of Geissospermum reticulatum Bark

    Science.gov (United States)

    Barnes, Nicholas M.; Wawer, Iwona; Paradowska, Katarzyna

    2016-01-01

    Geissospermum species are medically important plants due to their health-promoting effects. The objective of this study was to determine the antioxidant ability and antiproliferative and cytotoxic effects of infusions, tinctures, and ethanolic extracts of Geissospermum reticulatum barks in relation to the contents of total phenolics and flavonoids. Seven samples of barks were collected in various regions of Peruvian Amazonia. We found that the amount of total phenolics in the studied products varied from 212.40 ± 0.69 to 1253.92 ± 11.20 mg GAE/kg. In our study there is a correlation (R2 = 0.7947) between the results of antioxidants assays: FRAP and ORAC for tinctures, infusions, and ethanolic extracts of G. reticulatum barks. We have also observed antiproliferative activities of the ethanolic extracts on normal T-cells. These extracts have caused death on malignant cell lines (THP-1 and HL-60) and this data correlates well with their antioxidant capacity measured by ORAC method. Interestingly, the highest concentration of the ethanolic extract was not toxic in the zebrafish embryo developmental assay. Our results indicate that G. reticulatum is rich in antioxidants and have cytotoxic and antiproliferative properties. The data suggests potential immunosuppressive role of the extracts. This is the first study presenting the results of chemical and biological analysis of multiple preparations from G. reticulatum.

  10. Low-density microarray analysis of TGFβ1-dependent cell cycle regulation in human breast adenocarcinoma MCF7 cell line

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    Dubrovska A. M.

    2014-03-01

    Full Text Available Transforming growth factor β1 (TGFβ1 is a growth regulator that has antiproliferative effects on a range of epithelial cells at the early stages and promoting tumorigenesis at the later stages of cancer progression. The molecular mechanisms of a duel role of TGFβ1 in tumor growth regulation remain poorly understood. Aim. To analyze the TGFβ1-dependent cell cycle regulation of tumorigenic breast epithelial cells. Methods. Our present study was designed to examine the regulatory effect of TGFβ1 on the expression of a panel of 96 genes which are known to be critically involved in cell cycle regulation. GEArray Q series Human Cell Cycle Gene Array was applied to profile the gene expression changes in MCF7 human breast adenocarcinoma cell line treated with TGFβ1. Results. The gene expression array data enabled us to reveal the molecular regulators that might connect TGFβ1 signaling to the promoting of the tumor growth, e. g. retinoblastoma protein (pRB1, check-point kinase 2 (Chk2, breast cancer 1, early onset (BRCA1, DNA damage checkpoint protein RAD9, cyclin-dependent kinase 2 (CDK2, cyclin D1 (CCND1. Conclusions. The uncovering of the key signaling modules involved in TGFβ1- dependent signaling might provide an insight into the mechanisms of TGFβ1-dependent tumor growth and can be beneficial for the development of novel therapeutic approaches.

  11. In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Paula; M.Kustiawan; Songchan; Puthong; Enos; T.Arung; Chanpen; Chanchao

    2014-01-01

    Objective:To screen crude extracts of propolis,bee pollen and honey from four stingless bee species[Trigona incisa(T.incisa)],Timia apicalis,Trigona fuso-baltata and Trigona filscibasis)native to East Kalimantan.Indonesia for cytotoxic activity against five human cancer cell lines(HepG2,SW620,ChaGo-1,KATO-Ⅲand BT474).Methods:All samples were extracted with methanol,and then subpartitioned with n-hexane and ethyl acetate.Each crude extract was screened at 20μg/mL for in vitro cytotoxicity against the cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Tn addition,four previously shown bioactive components from propolis(apigenin,cafieic acid phenyl ester,kaempferol and naringenin)and two chemotherapeutic drugs(doxorubicin and 5-fluorouracil)were used to evaluate the sensitivity of the cell lines.Results:Overall,crude extracts from propolis and honey had higher cytotoxic activities than bee pollen,but the activity was dependent upon the extraction solvent,bee species and cell line.Propolis extracts from T.incisa and Tarda apicalis showed the highest and lowest cytotoxic activity,respectively.Only the HepG2 cell line was broadly sensitive to the honey extracts.For pure compounds,doxorubicin was the most cytotoxic,the four propolis compounds the least,but the ChaGo-I cell line was sensitive to kaempferol at 10μg/mL and KATO-Ⅲwas sensitive to kaempferol and apigenin at 10μg/mL,.All pure compounds were effective against the BT474 cell line.Conclusions:Propolis from f,incisa and Trigona fusco-balteata contain an in vitro cytotoxic activity against human cancer cell lines.Further study is required,including the isolation and characterization of the active antiproliferative agent(s).

  12. Determination of in vitro free radical scavenging and antiproliferative effect of Pennisetum alopecuroides on cultured A549 human lung cancer cells

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    Githa Elizabeth Mathew

    2015-01-01

    Conclusions: This is the 1 st time a pharmacological exploration of P. alopecuroides grasses has been conducted. We have shown that P. alopecuroides exhibits good free radical scavenging and strong in vitro cytotoxic activities against human lung cancer cell lines.

  13. Effects of berberine on proliferation, cell cycle distribution and apoptosis of human breast cancer T47D and MCF7 cell lines

    Science.gov (United States)

    Barzegar, Elmira; Fouladdel, Shamileh; Movahhed, Tahereh Komeili; Atashpour, Shekoufeh; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Azizi, Ebrahim

    2015-01-01

    Objective(s): Berberine, a naturally occurring isoquinoline alkaloid, has shown antitumor properties in some in vitro systems. But the effect of berberine on breast cancer has not yet been completely studied. In this study, we evaluated anticancer properties of berberine in comparison to doxorubicin. Materials and Methods: The antiproliferative effects of berberine and doxorubicin alone and in combination were evaluated in T47D and MCF7 cell lines using MTT cytotoxicity assay. In addition, flow cytometry analysis was performed to evaluate the cell cycle alteration and apoptosis induction in these cell lines following exposure to berberine and doxorubicin alone and in combination. Results: The IC50 of berberine was determined to be 25 µM after 48 hr of treatment in both cell lines but for doxorubicin it was 250 nM and 500 nM in T47D and MCF-7 cell lines, respectively. Co-treatment with berberine and doxorubicin increased cytotoxicity in T47D cells more significantly than in MCF-7 cells. Flow cytometry results demonstrated that berberine alone or in combination with doxorubicin induced G2/M arrest in the T47D cells, but G0/G1 arrest in the MCF-7 cells. Doxorubicin alone induced G2/M arrest in both cell lines. Furthermore, berberine and doxorubicin alone or in combination significantly induced apoptosis in both cell lines. Conclusion: Berberine alone and in combination with doxorubicin inhibited cell proliferation, induced apoptosis and altered cell cycle distribution of breast cancer cells. Therefore, berberine showed to be a good candidate for further studies as a new anticancer drug in the treatment of human breast cancer. PMID:26019795

  14. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents.

    Science.gov (United States)

    Zhang, Sai-Yang; Fu, Dong-Jun; Yue, Xiao-Xin; Liu, Ying-Chao; Song, Jian; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-05-19

    A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma.

  15. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents.

    Science.gov (United States)

    Zhang, Sai-Yang; Fu, Dong-Jun; Yue, Xiao-Xin; Liu, Ying-Chao; Song, Jian; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-01-01

    A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma. PMID:27213317

  16. Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents

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    Sai-Yang Zhang

    2016-05-01

    Full Text Available A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803. Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma.

  17. Cytotoxicity and Antiproliferative Activity Assay of Clove Mistletoe (Dendrophthoe pentandra (L.) Miq.) Leaves Extracts.

    Science.gov (United States)

    Elsyana, Vida; Bintang, Maria; Priosoeryanto, Bambang Pontjo

    2016-01-01

    Clove mistletoe (Dendrophthoe pentandra (L.) Miq.) is a semiparasitic plant that belongs to Loranthaceae family. Clove mistletoe was traditionally used for cancer treatment in Indonesia. In the present study, we examined cytotoxicity of clove mistletoe leaves extracts against brine shrimps and conducted their antiproliferative activity on K562 (human chronic myelogenous leukemia) and MCM-B2 (canine benign mixed mammary) cancer cell lines in vitro. The tested samples were water extract, ethanol extract, ethanol fraction, ethyl acetate fraction, and n-hexane fraction. Cytotoxicity was screened using Brine Shrimp Lethality Test (BSLT). Antiproliferative activity was conducted using Trypan Blue Dye Method and cells were counted using haemocytometer. The results showed that n-hexane fraction exhibited significant cytotoxicity with LC50 value of 55.31 μg/mL. The n-hexane fraction was then considered for further examination. The n-hexane fraction of clove mistletoe could inhibit growth of K562 and MCM-B2 cancer cell lines in vitro. The inhibition activity of clove mistletoe n-hexane fraction at concentration of 125 μg/mL on K562 cancer cell lines was 38.69%, while on MCM-B2 it was 41.5%. Therefore, it was suggested that clove mistletoe had potential natural anticancer activity. PMID:27099614

  18. Synthesis, Half-Wave Potentials and Antiproliferative Activity of 1-Aryl-substituted Aminoisoquinolinequinones

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    Juana Andrea Ibacache

    2014-01-01

    Full Text Available The synthesis of a variety of 1-aryl-7-phenylaminoisoquinolinequinones from 1,4-benzoquinone and arylaldehydes via the respective 1-arylisoquinolinequinones is reported. The cyclic voltammograms of the new compounds exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasi-reversible oxidation peaks. The half-wave potential values (EI½ of the members of the series have proven sensitive to the electron-donor effect of the aryl group (phenyl, 2-thienyl, 2-furyl at the 1-position as well as to the phenylamino groups (anilino, p-anisidino at the 7-position. The antiproliferative activity of the new compounds was evaluated in vitro using the MTT colorimetric method against one normal cell line (MRC-5 lung fibroblasts and two human cancer cell lines: AGS human gastric adenocarcinoma and HL-60 human promyelocytic leukemia cells in 72-h drug exposure assays. Among the series, compounds 5a, 5b, 5g, 5h, 6a and 6d exhibited interesting antiproliferative activities against human gastric adenocarcinoma. The 1-arylisoquinolinequinone 6a was found to be the most promising active compound against the tested cancer cell lines in terms of IC50 values (1.19; 1.24 µM and selectivity index (IS: 3.08; 2.96, respect to the anti-cancer agent etoposide used as reference (IS: 0.57; 0.14.

  19. Betanin a betacyanin pigment purified from fruits of Opuntia ficus-indica induces apoptosis in human chronic myeloid leukemia Cell line-K562.

    Science.gov (United States)

    Sreekanth, Devalraju; Arunasree, M K; Roy, Karnati R; Chandramohan Reddy, T; Reddy, Gorla V; Reddanna, Pallu

    2007-11-01

    Betalains are water-soluble nitrogenous vacuolar pigments present in flowers and fruits of many caryophyllales with potent antioxidant properties. In the present study the antiproliferative effects of betanin, a principle betacyanin pigment, isolated from the fruits of Opuntia ficus-indica, was evaluated on human chronic myeloid leukemia cell line (K562). The results show dose and time dependent decrease in the proliferation of K562 cells treated with betanin with an IC(50) of 40 microM. Further studies involving scanning and transmission electron microscopy revealed the apoptotic characteristics such as chromatin condensation, cell shrinkage and membrane blebbing. Agarose electrophoresis of genomic DNA of cells treated with betanin showed fragmentation pattern typical for apoptotic cells. Flow cytometric analysis of cells treated with 40 microM betanin showed 28.4% of cells in sub G0/G1 phase. Betanin treatment to the cells also induced the release of cytochrome c into the cytosol, poly (ADP) ribose polymerase (PARP) cleavage, down regulation Bcl-2, and reduction in the membrane potentials. Confocal microscopic studies on the cells treated with betanin suggest the entry of betanin into the cells. These studies thus demonstrate that betanin induces apoptosis in K562 cells through the intrinsic pathway and is mediated by the release of cytochrome c from mitochondria into the cytosol, and PARP cleavage. The antiproliferative effects of betanin add further value to the nutritional characteristics of the fruits of O. ficus-indica.

  20. Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf Extract of Holarrhena floribunda (G. Don

    Directory of Open Access Journals (Sweden)

    J. A. Badmus

    2015-01-01

    Full Text Available Natural plant products with potent growth inhibition and apoptosis induction properties are extensively being investigated for their cancer chemopreventive potential. Holarrhena floribunda (HF is used in a wide range of traditional medicine practices. The present study investigated the antiproliferative and apoptosis induction potential of methanolic leaf extracts of HF against breast (MCF-7, colorectal (HT-29, and cervical (HeLa cancer cells relative to normal KMST-6 fibroblasts. The MTT assay in conjunction with the trypan blue dye exclusion and clonogenic assays were used to determine the effects of the extracts on the cells. Caspase activities were assayed with Caspase-Glo 3/7 and Caspase-9 kits. Apoptosis induction was monitored by flow cytometry using the APOPercentage and Annexin V-FITC kits. Reactive oxygen species (ROS was measured using the fluorogenic molecular probe 5-(and-6-chloromethyl-2′,7′-dichlorofluorescein diacetate acetyl ester and cell cycle arrest was detected with propidium iodide. Dose-response analyses of the extract showed greater sensitivity in cancer cell lines than in fibroblast controls. Induction of apoptosis, ROS, and cell cycle arrest were time- and dose-dependent for the cancer cell lines studied. These findings provide a basis for further studies on the isolation, characterization, and mechanistic evaluation of the bioactive compounds responsible for the antiproliferative activity of the plant extract.

  1. Lycium europaeum fruit extract: antiproliferative activity on A549 human lung carcinoma cells and PC12 rat adrenal medulla cancer cells and assessment of its cytotoxicity on cerebellum granule cells.

    Science.gov (United States)

    Ghali, Wafa; Vaudry, David; Jouenne, Thierry; Marzouki, Mohamed Nejib

    2015-01-01

    Cancer is a major worldwide health problem and one of the leading causes of death either in developed or developing countries. Plant extracts and derivatives have always been used for various disease treatments and many anticancer agents issued from plants and vegetables are clinically recognized and used all over the world. Lycium europaeum (Solanaceae) also called "wolfberry" was known since ancient times in the Mediterranean area as a medicinal plant and used in several traditional remedies. The Lycium species capacity of reducing the incidence of cancer and also of halting or reserving the growth of cancer was reported by traditional healers. In this study, the antiproliferative capacity, protective properties, and antioxidant activity of the hydro-alcoholic fruit extract of Lycium europaeum were investigated. Results showed that Lycium extract exhibits the ability to reduce cancer cell viability, inhibits proliferation, and induces apoptosis in A549 human lung cancer cells and PC12 rat adrenal medulla cancer cells, in a concentration- and time-dependent manner. Cytotoxic effect on normal rat cerebellum granule cells was assessed to be nonsignificant. Results also showed that Lycium fruit extract protected lipids, proteins, and DNA against oxidative stress damages induced by H2O2 via scavenging reactive oxygen species.

  2. Comparison of Cytotoxic and Antiproliferative Effects of Benzylidenecyclopentanone Analogues of Curcumin on RBL-2H3 Cells

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    Agung Endro Nugroho

    2015-11-01

    Full Text Available Curcumin is a natural yellow pigment isolated from the rhizomes of Curcuma longa L. (turmeric, and has several pharmacological effects and no toxicity in both in animal and human clinical study. However, the problem of curcumin is its stability because of its active methylene moiety. Modification of this moiety to cyclopentanone is expected to increase the stability. Previous study reported that benzylidenecyclopentanone analogues of curcumin showed inhibitory effect on histamine release from RBL-2H3 (rat basophilic leukemia cells, a tumor analog of mast cells. One of them, the hydroxy-methoxy analog (PGV-0, showed more potent effect than that of curcumin. In the present study, some benzylidenecyclopentanone analogues of curcumin were evaluated for their effects on the viability and proliferation of RBL-2H3 cells. Viable cells were counted under a light microscope with a cells-counting chamber or using the cell viability reagent WST-1. The results showed that mast cell viability and histamine content were not affected by curcumin and benzylidene cyclopentanone for 30 min incubation, however, impaired for overnight incubation. The hydroxy-dimethyl benzylidene analog (PGV-1 strongly decreased the mast cells viability for overnight incubation, and its effect was highest among the other analogues. In the proliferation study, this compound also strongly inhibited the proliferation of mast cells, whereas curcumin and hydroxy-methoxy benzylidene analog inhibited the proliferation slightly. There were no inhibitory effects on mast cells proliferation treated by dibenzylidene; dihydroxybenzylidene; and hydroxy-diethylbenzylidene cyclopentanone.Keywords : viability, proliferation, curcumin, benzylidene cyclopentanone, RBL-2H3 cells

  3. Antiproliferative and Proapoptotic Effects of Labisia pumila Ethanol Extract and Its Active Fraction in Human Melanoma HM3KO Cells.

    Science.gov (United States)

    Lope Pihie, Azimahtol Hawariah; Zakaria, Zainul Amiruddin; Othman, Fezah

    2012-01-01

    The present study was to determine the anticancer potential of Labisia pumila in in vitro models. Results from the study revealed that ethanol extract of L. pumila was more cytotoxic against HM3KO cells while having reduced effects on nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol extract was selected to be further separated by using the bioassay-guided fractionation method to give an active fraction, SF2Lp. Results obtained from the flow cytometry analysis showed that SF2Lp was able to arrest the HM3KO cell cycle at the G1 phase, while morphological findings from AO-EB nuclear staining assays along with the Apoptotic Index confirmed the induction of apoptosis by SF2Lp in HM3KO cells. Results from the mechanistic study further revealed that SF2Lp treatment was able to concurrently increase the expression level of p53 and pro-apoptotic protein Bax and also reduce the expression level of anti-apoptotic protein BCl-2 in HM3KO cells, directly contributing to the increase in Bax/Bcl-2 ratio. These findings, therefore, suggested that L. pumila was able to inhibit HM3KO cell growth possibly by arresting the cell cycle at G1 phase and inducing apoptosis in HM3KO cells via the up- and down-regulation of Bax/Bcl-2 protein, mediated through a p53-dependent pathway. PMID:22474490

  4. Antiproliferative and Proapoptotic Effects of Labisia pumila Ethanol Extract and Its Active Fraction in Human Melanoma HM3KO Cells

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    Azimahtol Hawariah Lope Pihie

    2012-01-01

    Full Text Available The present study was to determine the anticancer potential of Labisia pumila in in vitro models. Results from the study revealed that ethanol extract of L. pumila was more cytotoxic against HM3KO cells while having reduced effects on nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol extract was selected to be further separated by using the bioassay-guided fractionation method to give an active fraction, SF2Lp. Results obtained from the flow cytometry analysis showed that SF2Lp was able to arrest the HM3KO cell cycle at the G1 phase, while morphological findings from AO-EB nuclear staining assays along with the Apoptotic Index confirmed the induction of apoptosis by SF2Lp in HM3KO cells. Results from the mechanistic study further revealed that SF2Lp treatment was able to concurrently increase the expression level of p53 and pro-apoptotic protein Bax and also reduce the expression level of anti-apoptotic protein BCl-2 in HM3KO cells, directly contributing to the increase in Bax/Bcl-2 ratio. These findings, therefore, suggested that L. pumila was able to inhibit HM3KO cell growth possibly by arresting the cell cycle at G1 phase and inducing apoptosis in HM3KO cells via the up- and down-regulation of Bax/Bcl-2 protein, mediated through a p53-dependent pathway.

  5. Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction.

    Science.gov (United States)

    Yen, Ching-Yu; Chiu, Chien-Chih; Haung, Rou-Wen; Yeh, Chi-Chen; Huang, Kuang-Jing; Chang, Kuo-Feng; Hseu, You-Cheng; Chang, Fang-Rong; Chang, Hsueh-Wei; Wu, Yang-Chang

    2012-09-18

    Goniothalamin (GTN), a plant bioactive styryl-lactone, is a natural product with potent anti-tumorigenesis effects for several types of cancer. Nonetheless, the anticancer effect of GTN has not been examined in oral cancer. The present study was designed to evaluate its potential anticancer effects in an oral squamous cell carcinoma (OSCC) model and to determine the possible mechanisms with respect to apoptosis, DNA damage, reactive oxygen species (ROS) induction, and mitochondrial membrane potential. Our data demonstrated that cell proliferation was significantly inhibited by GTN in Ca9-22 OSCC cancer cells in concentration- and time-dependent manners (pGTN-treated Ca9-22 cancer cells, the sub-G1 population and annexin V-intensity significantly increased in a concentration-dependent manner (pGTN-treated Ca9-22 cancer cells in concentration-response relationship (pGTN significantly induced intracellular ROS levels in Ca9-22 cancer cells in a concentration- and time-dependent manner (pGTN-treated Ca9-22 cancer cells was significantly decreased in concentration- and time-dependent relationships (pGTN against oral cancer cells is valid and GTN-induced growth inhibition and apoptosis influence the downstream cascade including ROS induction, DNA damage, and mitochondria membrane depolarization. Therefore, GTN has potential as a chemotherapeutic agent against oral cancer.

  6. The Synthesis and Antiproliferative Activities of New Arylidene-Hydrazinyl-Thiazole Derivatives

    Directory of Open Access Journals (Sweden)

    Adriana Grozav

    2014-12-01

    Full Text Available New and known arylidene-hydrazinyl-thiazole derivatives have been synthesized by a convenient Hantzsch condensation. All compounds were evaluated for their in vitro cytotoxicity on two carcinoma cell lines, MDA-MB231 and HeLa. Significant antiproliferative activity for 2-(2-benzyliden-hydrazinyl-4-methylthiazole on both MDA-MB-231 (IC50: 3.92 µg/mL and HeLa (IC50: 11.4 µg/mL cell lines, and for 2-[2-(4-methoxybenzylidene hydrazinyl]-4-phenylthiazole on HeLa (IC50: 11.1 µg/mL cell line is reported. Electrophoresis experiments showed no plasmid DNA (pTZ57R cleavage in the presence of the investigated thiazoles.

  7. The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines

    Directory of Open Access Journals (Sweden)

    Bajbouj Khuloud

    2012-05-01

    Full Text Available Abstract Background Saffron extract, a natural product, has been shown to induce apoptosis in several tumor cell lines. Nevertheless, the p53-dependency of saffron’s mechanism of action in colon cancer remains unexplored. Material and methods In order to examine saffron’s anti-proliferative and pro-apoptotic effects in colorectal cancer cells, we treated two p53 isogenic HCT116 cell lines (HCT wildtype and HCT p53−/− with different doses of the drug and analyzed cell proliferation and apoptosis in a time-dependent manner. MTT viability and crystal violet assays were performed in order to determine the effective dose of saffron on both cell lines. The cell cycle progress was examined by Flow cytometric analysis. Apoptosis was assessed using Annexin-PI-staining and Western Blotting for caspase 3 and PARP cleavage. Autophagy was determined by Western Blotting of the light chain 3 (LC3-II and Beclin 1 proteins. The protein content of phospho-H2AX (γH2AX, a sensor of DNA double strand breaks, was also analyzed by Western Blotting. Results Saffron extract induced a p53-dependent pattern of cell cycle distribution with a full G2/M stop in HCT116 p53 wildtype cells. However, it induced a remarkable delay in S/G2 phase transit with entry into mitosis in HCT116 p53 −/− cells. The apoptotic Pre-G1 cell fraction as well as Annexin V staining and caspase 3 cleavage showed a more pronounced apoptosis induction in HCT116 p53 wildtype cells. Obviously, the significantly higher DNA-damage, reflected by ɣH2AX protein levels in cells lacking p53, was coped by up-regulation of autophagy. The saffron-induced LC3-II protein level was a remarkable indication of the accumulation of autophagosomes, a response to the cellular stress condition of drug treatment. Conclusions This is the first study showing the effect of saffron in HCT116 colorectal cancer cells with different p53 status. Saffron induced DNA-damage and apoptosis in both cell lines. However

  8. Susceptibility testing of fish cell lines for virus isolation

    DEFF Research Database (Denmark)

    Ariel, Ellen; Skall, Helle Frank; Olesen, Niels Jørgen

    2009-01-01

    compare susceptibility between cell lines and between lineages within a laboratory and between laboratories (Inter-laboratory Proficiency Test). The objective being that the most sensitive cell line and lineages are routinely selected for diagnostic purposes.In comparing cell lines, we simulated "non......-cell-culture-adapted" virus by propagating the virus in heterologous cell lines to the one tested. A stock of test virus was produced and stored at - 80 °C and tests were conducted biannually. This procedure becomes complicated when several cell lines are in use and does not account for variation among lineages. In comparing...... cell lineages, we increased the number of isolates of each virus, propagated stocks in a given cell line and tested all lineages of that line in use in the laboratory. Testing of relative cell line susceptibility between laboratories is carried out annually via the Inter-laboratory Proficiency Test...

  9. Anti-proliferative effect of rhein, an anthraquinone isolated from Cassia species, on Caco-2 human adenocarcinoma cells.

    Science.gov (United States)

    Aviello, Gabriella; Rowland, Ian; Gill, Christopher I; Acquaviva, Angela Maria; Capasso, Francesco; McCann, Mark; Capasso, Raffaele; Izzo, Angelo A; Borrelli, Francesca

    2010-07-01

    In recent years, the use of anthraquinone laxatives, in particular senna, has been associated with damage to the intestinal epithelial layer and an increased risk of developing colorectal cancer. In this study, we evaluated the cytotoxicity of rhein, the active metabolite of senna, on human colon adenocarcinoma cells (Caco-2) and its effect on cell proliferation. Cytotoxicity studies were performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and trans-epithelial electrical resistance (TEER) assays whereas (3)H-thymidine incorporation and Western blot analysis were used to evaluate the effect of rhein on cell proliferation. Moreover, for genoprotection studies Comet assay and oxidative biomarkers measurement (malondialdehyde and reactive oxygen species) were used. Rhein (0.1-10 microg/ml) had no significant cytotoxic effect on proliferating and differentiated Caco-2 cells. Rhein (0.1 and 1 microg/ml) significantly reduced cell proliferation as well as mitogen-activated protein (MAP) kinase activation; by contrast, at high concentration (10 microg/ml) rhein significantly increased cell proliferation and extracellular-signal-related kinase (ERK) phosphorylation. Moreover, rhein (0.1-10 microg/ml): (i) did not adversely affect the integrity of tight junctions and hence epithelial barrier function; (ii) did not induce DNA damage, rather it was able to reduce H(2)O(2)-induced DNA damage and (iii) significantly inhibited the increase in malondialdehyde and reactive oxygen species (ROS) levels induced by H(2)O(2)/Fe(2+). Rhein was devoid of cytotoxic and genotoxic effects in colon adenocarcinoma cells. Moreover, at concentrations present in the colon after a human therapeutic dosage of senna, rhein inhibited cell proliferation via a mechanism that seems to involve directly the MAP kinase pathway. Finally, rhein prevents the DNA damage probably via an anti-oxidant mechanism.

  10. Antiproliferative and Proapoptotic Effects of Labisia pumila Ethanol Extract and Its Active Fraction in Human Melanoma HM3KO Cells

    OpenAIRE

    Lope Pihie, Azimahtol Hawariah; Zakaria, Zainul Amiruddin; Othman, Fezah

    2012-01-01

    The present study was to determine the anticancer potential of Labisia pumila in in vitro models. Results from the study revealed that ethanol extract of L. pumila was more cytotoxic against HM3KO cells while having reduced effects on nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol extract was selected to be further separated by using the bioassay-guided fractionation method to give an active fraction, SF2Lp. Results obtained from the flow cytometry analysis showe...

  11. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells

    OpenAIRE

    Maruša Rajh; Klemen Dolinar; Katarina Miš; Mojca Pavlin; Sergej Pirkmajer

    2016-01-01

    Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct ant...

  12. Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray

    OpenAIRE

    Zi-Yin Shen; Jing-Cheng Dong; Xin-Min Zhang; Yang Chen; Qin Bian; Shi-Jin Xia; Jian-Hua Huang; You Ning

    2013-01-01

    Adult neural stem cells (NSCs) persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS) injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit of Psoralea corylifolia ...

  13. ANTIPROLIFERATIVE AND APOPTOTIC EFFECTS OF THE ESSENTIAL OIL OF ORIGANUM ONITES AND CARVACROL ON HEP-G2 CELLS

    Directory of Open Access Journals (Sweden)

    Özlem TOMSUK

    2011-08-01

    Full Text Available The essential oil Origanum onites L. and its phenolic constituent carvacrol were examined for their cytotoxic and apoptotic effects in a human hepatocellular carcinoma cells Hep-G2. WST-1 and neutral red uptake assays were performed to determine the inhibitory effects of the oil and carvacrol on the growth of the cells. Possible induction of apoptosis by Origanum oil and carvacrol was further investigated by acridine orange/ethidium bromide (AO/EB staining. Results showed that the Ori- ganum oil and carvacrol was significantly cytotoxic and induced apoptosis in Hep-G2 cells. IC₅₀ value of essential oil and carvacrol was found about 0,009% (v/v and 500 μM, respectively. After incuba- tion of the cells with Origanum oil and carvacrol, characteristics of apoptotic morphology such as chromatin condensation, shrinkage of the cells and cytoplasmic blebbing was observed. In conclusion, both essential oil and its major constituent carvacrol significantly exhibited cytotoxic and apoptotic activities in hepatocellular carcinoma cells, indicating its potential for use as an anticancer agent.

  14. Antiproliferative activity of the dietary isothiocyanate erucin, a bioactive compound from cruciferous vegetables, on human prostate cancer cells.

    Science.gov (United States)

    Melchini, Antonietta; Traka, Maria H; Catania, Stefania; Miceli, Natalizia; Taviano, Maria Fernanda; Maimone, Patrizia; Francisco, Marta; Mithen, Richard F; Costa, Chiara

    2013-01-01

    It is becoming increasingly clear that many dietary agents, such as isothiocyanates (ITCs) from cruciferous vegetables, can retard or prevent the process of prostate carcinogenesis. Erucin (ER) is a dietary ITC, which has been recently considered a promising cancer chemopreventive phytochemical. The potential protective activity of ER against prostate cancer was investigated using prostate adenocarcinoma cells (PC3), to analyze its effects on pathways involved in cell growth regulation, such as the cyclin-dependent kinase (CDKs) inhibitor p21(WAF1/CIP1) (p21), phosphatidylinositol-3 kinase/AKT, and extracellular signal-regulated kinases (ERK)1/2 signaling pathways. We have shown for the first time that ER increases significantly p21 protein expression and ERK1/2 phosphorylation in a dose-dependent manner to inhibit PC3 cell proliferation (P ≤ 0.01). Compared to the structurally related sulforaphane, a well-studied broccoli-derived ITC, ER showed lower potency in inhibiting proliferation of PC3 cells, as well as in modulating p21 and pERK1/2 protein levels. Neither of the naturally occurring ITCs was able to affect significantly pAKT protein levels in prostate cells at all concentrations tested (0-25 μM). It is clearly important for the translation of laboratory findings to clinical approaches to investigate in animal and cell studies the molecular mechanisms by which ITCs may exert health promoting effects.

  15. Lichen metabolites. 2. Antiproliferative and cytotoxic activity of gyrophoric, usnic, and diffractaic acid on human keratinocyte growth.

    Science.gov (United States)

    Kumar, K C; Müller, K

    1999-06-01

    The sensitivity of the human keratinocyte cell line HaCaT to several lichen metabolites isolated from Parmelia nepalensis and Parmelia tinctorum was evaluated. The tridepside gyrophoric acid (6), the dibenzofuran derivative (+)-usnic acid (1), and the didepside diffractaic acid (5) were potent antiproliferative agents and inhibited cell growth, with IC50 values of 1.7, 2.1, and 2.6 microM, respectively. Methyl beta-orcinolcarboxylate (2), ethyl hematommate (3), the didepside atranorin (4), and (+)-protolichesterinic acid (7) did not influence keratinocyte growth at concentrations of 5 microM. Keratinocytes were further tested for their susceptibility to the action of the potent antiproliferative agents on plasma membrane integrity. The release of lactate dehydrogenase activity into the culture medium was unchanged as compared to controls, documenting that the activity of gyrophoric acid (6), (+)-usnic acid (1), and diffractaic acid (5) was due to cytostatic rather than cytotoxic effects. PMID:10395495

  16. In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae

    Directory of Open Access Journals (Sweden)

    A.S.N. Formagio

    2015-04-01

    Full Text Available The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI50 values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI50 values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%. Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

  17. In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae.

    Science.gov (United States)

    Formagio, A S N; Vieira, M C; Volobuff, C R F; Silva, M S; Matos, A I; Cardoso, C A L; Foglio, M A; Carvalho, J E

    2015-04-01

    The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE) inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI50) values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI50 values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%). Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

  18. In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae

    Energy Technology Data Exchange (ETDEWEB)

    Formagio, A.S.N.; Vieira, M.C. [Faculdade de Ciências Agrárias, Universidade Federal da Grande Dourados, Dourados, MS (Brazil); Volobuff, C.R.F.; Silva, M.S. [Faculdade de Ciências Biológicas e Ambientais, Universidade Federal da Grande Dourados, Dourados, MS (Brazil); Matos, A.I. [Faculdade de Ciências, Universidade de Lisboa, Lisboa (Portugal); Cardoso, C.A.L. [Curso de Química, Universidade Estadual do Mato Grosso do Sul, Dourados, MS (Brazil); Foglio, M.A.; Carvalho, J.E. [Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2015-02-13

    The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE) inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI{sub 50}) values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI{sub 50} values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%). Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

  19. Regulatory networks define phenotypic classes of human stem cell lines

    OpenAIRE

    Müller, Franz-Josef; Louise C. Laurent; Kostka, Dennis; Ulitsky, Igor; Williams, Roy; Lu, Christina; Park, In-Hyun; Rao, Mahendra S.; Shamir, Ron; Philip H. Schwartz; Schmidt, Nils O.; Loring, Jeanne F.

    2008-01-01

    Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal, and adult sources have been called stem cells, even though they range from pluripotent cells, typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation, to adult stem cell lines, which can generate a far more limited repertory of differentiated cell types. The...

  20. Characteristics of nobiletin-mediated alteration of gene expression in cultured cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Nemoto, Kiyomitsu, E-mail: nemoto@u-shizuoka-ken.ac.jp [Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan); Ikeda, Ayaka; Yoshida, Chiaki; Kimura, Junko; Mori, Junki [Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan); Fujiwara, Hironori [Department of Anti-Dementia Functional Food Development, Research Center of Supercritical Fluid Technology, Graduate School of Engineering, Tohoku University, 6-6-7 Aoba, Aramaki, Aoba-ku, Sendai 980-8579 (Japan); Yokosuka, Akihito; Mimaki, Yoshihiro [Department of Medicinal Pharmacognosy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392 (Japan); Ohizumi, Yasushi [Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan); Department of Anti-Dementia Functional Food Development, Research Center of Supercritical Fluid Technology, Graduate School of Engineering, Tohoku University, 6-6-7 Aoba, Aramaki, Aoba-ku, Sendai 980-8579 (Japan); Laboratory of Kampo Medicines, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066 (Japan); Degawa, Masakuni [Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan)

    2013-02-15

    Highlights: ► Nobiletin-mediated alterations of gene expression were examined with DNA microarrays. ► Three organ-derived cell lines were treated with 100 μM nobiletin for 24 h. ► In all cell lines, 3 endoplasmic reticulum stress-responsive genes were up-regulated. ► Some cell cycle-regulating and oxidative stress-promoting genes were down-regulated. ► These alterations may contribute to nobiletin-mediated biological effects. -- Abstract: Nobiletin, a polymethoxylated flavonoid that is highly contained in the peels of citrus fruits, exerts a wide variety of beneficial effects, including anti-proliferative effects in cancer cells, repressive effects in hyperlipidemia and hyperglycemia, and ameliorative effects in dementia at in vitro and in vivo levels. In the present study, to further understand the mechanisms of these actions of nobiletin, the nobiletin-mediated alterations of gene expression in three organ-derived cell lines – 3Y1 rat fibroblasts, HuH-7 human hepatocarcinoma cells, and SK-N-SH human neuroblastoma cells – were first examined with DNA microarrays. In all three cell lines, treatments with nobiletin (100 μM) for 24 h resulted in more than 200% increases in the expression levels of five genes, including the endoplasmic reticulum stress-responsive genes Ddit3, Trib3, and Asns, and in less than 50% decreases in the expression levels of seven genes, including the cell cycle-regulating genes Ccna2, Ccne2, and E2f8 and the oxidative stress-promoting gene Txnip. It was also confirmed that in each nobiletin-treated cell line, the levels of the DDIT3 (DNA-damage-inducible transcript 3, also known as CHOP and GADD153) and ASNS (asparagine synthetase) proteins were increased, while the level of the TXNIP (thioredoxin-interacting protein, also known as VDUP1 and TBP-2) protein was decreased. All these findings suggest that nobiletin exerts a wide variety of biological effects, at least partly, through induction of endoplasmic reticulum stress and

  1. Antimicrobial Activity of Essential Oils against Streptococcus mutans and their Antiproliferative Effects

    Directory of Open Access Journals (Sweden)

    Lívia Câmara de Carvalho Galvão

    2012-01-01

    Full Text Available This study aimed to evaluate the activity of essential oils (EOs against Streptococcus mutans biofilm by chemically characterizing their fractions responsible for biological and antiproliferative activity. Twenty EO were obtained by hydrodistillation and submitted to the antimicrobial assay (minimum inhibitory (MIC and bactericidal (MBC concentrations against S. mutans UA159. Thin-layer chromatography and gas chromatography/mass spectrometry were used for phytochemical analyses. EOs were selected according to predetermined criteria and fractionated using dry column; the resulting fractions were assessed by MIC and MBC, selected as active fractions, and evaluated against S. mutans biofilm. Biofilms formed were examined using scanning electron microscopy. Selected EOs and their selected active fractions were evaluated for their antiproliferative activity against keratinocytes and seven human tumor cell lines. MIC and MBC values obtained for EO and their active fractions showed strong antimicrobial activity. Chemical analyses mainly showed the presence of terpenes. The selected active fractions inhibited S. mutans biofilm formation (P<0.05 did not affect glycolytic pH drop and were inactive against keratinocytes, normal cell line. In conclusion, EO showed activity at low concentrations, and their selected active fractions were also effective against biofilm formed by S. mutans and human tumor cell lines.

  2. Antimutagenic, antiproliferative, and antioxidant effect of extracts obtained from octopus (Paraoctopus limaculatus

    Directory of Open Access Journals (Sweden)

    Susana-Gabriela CRUZ-RAMÍREZ

    2015-12-01

    Full Text Available Abstract The search for chemopreventive/chemoprotective compounds in marine organism has been extensively reported; however, the presence of these compounds in octopus has been incipiently explored. In this research, the antimutagenic, antiproliferative, and antioxidant potential of three crude extracts (methanolic, acetonic, and hexanic from Paroctopus limaculatus was investigated. Antimutagenic activity against aflatoxin B1 (AFB1 was evaluated through the Ames test using Salmonella typhimurium tester strains TA98 and 100. Antiproliferative activity was assessed using the standard MTT (3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide assay on M12.C3.F6 murine cell line. Antioxidant activity was assessed using the DPPH (2,2-diphenyl-1-picrylhydrazyl and ABTS (2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid methods. Hexanic extract showed the highest antimutagenic and antiproliverative activities inhibiting 80 and 43% of mutagenicity induced by AFB1 for TA98 and TA100, respectively, and showing a high antiproliferative activity at 200 and 100 µg/mL. However, when the antioxidant activity was evaluated at a concentration of 50 mg/mL, the methanolic fraction exerted inhibition of 98 and 96 % ABTS and DPPH radicals, respectively. RP-HPLC and 1H-RMN analyses suggested the presence of double bonds with extended conjugation and oxygenated compounds such as alcohols, esters, ethers or ketones. These results suggested that hexanic and methanolic extract form octopus contained compounds with chemoprotective and antioxidant properties.

  3. Antiproliferative and Antioxidant Properties of Anthocyanin Rich Extracts from Blueberry and Blackcurrant Juice

    Directory of Open Access Journals (Sweden)

    Zoriţa Diaconeasa

    2015-01-01

    Full Text Available The present study was aimed at evaluating the antiproliferative potential of anthocyanin-rich fractions (ARFs obtained from two commercially available juices (blueberry and blackcurrant juices on three tumor cell lines; B16F10 (murine melanoma, A2780 (ovarian cancer and HeLa (cervical cancer. Individual anthocyanin determination, identification and quantification were done using HPLC-MS. Antioxidant activity of the juices was determined through different mechanism methods such as DPPH and ORAC. For biological testing, the juices were purified through C18 cartridges in order to obtain fractions rich in anthocyanins. The major anthocyanins identified were glycosylated cyanidin derivatives. The antiproliferative activity of the fractions was tested using the MTT assay. The antiproliferative potential of ARF was found to be associated with those bioactive molecules, anthocyanins due to their antioxidant potential. The results obtained indicated that both blueberry and blackcurrants are rich sources of antioxidants including anthocyanins and therefore these fruits are highly recommended for daily consumption to prevent numerous degenerative diseases.

  4. High prevalence of side population in human cancer cell lines

    OpenAIRE

    Boesch, Maximilian; Zeimet, Alain G; Fiegl, Heidi; Wolf, Barbara; Huber, Julia; Klocker, Helmut; Gastl, Guenther; Sopper, Sieghart; Wolf, Dominik

    2016-01-01

    Cancer cell lines are essential platforms for performing cancer research on human cells. We here demonstrate that, across tumor entities, human cancer cell lines harbor minority populations of putative stem-like cells, molecularly defined by dye extrusion resulting in the side population phenotype. These findings establish a heterogeneous nature of human cancer cell lines and argue for their stem cell origin. This should be considered when interpreting research involving these model systems.

  5. Expression of Cyclooxygenase-2 in Ovarian Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the expression of cyclooxygenase-2 (COX-2) in ovarian cancer cell lines,RT-PCR and immunocytochemistry were used to detect the expression of COX-2 in 5 ovarian cancer cell lines. The expression of COX-2 mRNA and protein was detected in all 5 cell lines. It is suggested that COX-2 is expressed in ovarian cancer cell lines, which provides a basis for the chemoprevention of ovarian cancer.

  6. Synthesis and In Vitro Antiproliferative Activity of Novel Androst-5-ene Triazolyl and Tetrazolyl Derivatives

    Directory of Open Access Journals (Sweden)

    János Wölfling

    2011-06-01

    Full Text Available A straightforward and reliable method for the regioselective synthesis of steroidal 1,4-disubstituted triazoles and 1,5-disubstituted tetrazoles via copper(I-catalyzed cycloadditions is reported. Heterocycle moieties were efficiently introduced onto the starting azide compound 3β-acetoxy-16β-azidomethylandrost-5-en-17β-ol through use of the “click” chemistry approach. The antiproliferative activities of the newly-synthesized triazoles were determined in vitro on three human gynecological cell lines (HeLa, MCF7 and A2780 using the microculture tetrazolium assay.

  7. Synthesis and in vitro antiproliferative activity of novel androst-5-ene triazolyl and tetrazolyl derivatives.

    Science.gov (United States)

    Kádár, Zalán; Kovács, Dóra; Frank, Éva; Schneider, Gyula; Huber, Judit; Zupkó, István; Bartók, Tibor; Wölfling, János

    2011-01-01

    A straightforward and reliable method for the regioselective synthesis of steroidal 1,4-disubstituted triazoles and 1,5-disubstituted tetrazoles via copper(I)-catalyzed cycloadditions is reported. Heterocycle moieties were efficiently introduced onto the starting azide compound 3β-acetoxy-16β-azidomethylandrost-5-en-17β-ol through use of the "click" chemistry approach. The antiproliferative activities of the newly-synthesized triazoles were determined in vitro on three human gynecological cell lines (HeLa, MCF7 and A2780) using the microculture tetrazolium assay. PMID:21659965

  8. Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung-Jin [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of); Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Zhang, Wei-Yun; Yi, Hyoseok; Kim, Yohan; Kim, In-Su [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of); Shen, Gui-Nan; Song, Gyu-Yong [Department of Medicinal Chemistry, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of); Myung, Chang-Seon, E-mail: cm8r@cnu.ac.kr [Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of); Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2011-07-22

    Highlights: {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner with no apparent cytotoxicity. {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced phosphorylation of Erk1/2 and PLC{gamma}1. {yields} 2-Decylamino-DMNQ arrested a G{sub 0}/G{sub 1} cell cycle progression in association with pRb phosphorylation and PCNA expression. {yields} Both U0126, an Erk inhibitor, and U73122, a PLC{gamma} inhibitor, arrested a G{sub 0}/G{sub 1} phase of the cell cycle. -- Abstract: Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-R{beta} or Akt, it did inhibit the phosphorylation of Erk1/2 and PLC{gamma}1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G{sub 0}/G{sub 1} phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLC{gamma} inhibitor, increased the proportion of cells in the G{sub 0}/G{sub 1} phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G{sub 0}/G{sub 1} phase. This may be a useful tool for studying interventions for vascular restenosis in coronary

  9. Design, synthesis and antiproliferative activity studies of novel dithiocarbamate-chalcone derivates.

    Science.gov (United States)

    Fu, Dong-Jun; Zhang, Sai-Yang; Liu, Ying-Chao; Zhang, Li; Liu, Jun-Ju; Song, Jian; Zhao, Ruo-Han; Li, Feng; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-08-15

    A series of novel dithiocarbamate-chalcone derivates were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell lines (EC-109, SK-N-SH and MGC-803). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds II2 and II5 exhibited the excellent growth inhibition against SK-N-SH with IC50 values of 2.03μM and 2.46μM, respectively. Further mechanism studies revealed that compound II2 could obviously inhibit the proliferation of SK-N-SH cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase. PMID:27423479

  10. The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds.

    Science.gov (United States)

    Sasi, Nanda Kumar; Tiwari, Kanchan; Soon, Fen-Fen; Bonte, Dorine; Wang, Tong; Melcher, Karsten; Xu, H Eric; Weinreich, Michael

    2014-01-01

    Cdc7-Dbf4 kinase or DDK (Dbf4-dependent kinase) is required to initiate DNA replication by phosphorylating and activating the replicative Mcm2-7 DNA helicase. DDK is overexpressed in many tumor cells and is an emerging chemotherapeutic target since DDK inhibition causes apoptosis of diverse cancer cell types but not of normal cells. PHA-767491 and XL413 are among a number of potent DDK inhibitors with low nanomolar IC50 values against the purified kinase. Although XL413 is highly selective for DDK, its activity has not been extensively characterized on cell lines. We measured anti-proliferative and apoptotic effects of XL413 on a panel of tumor cell lines compared to PHA-767491, whose activity is well characterized. Both compounds were effective biochemical DDK inhibitors but surprisingly, their activities in cell lines were highly divergent. Unlike PHA-767491, XL413 had significant anti-proliferative activity against only one of the ten cell lines tested. Since XL413 did not effectively inhibit DDK in multiple cell lines, this compound likely has limited bioavailability. To identify potential leads for additional DDK inhibitors, we also tested the cross-reactivity of ∼400 known kinase inhibitors against DDK using a DDK thermal stability shift assay (TSA). We identified 11 compounds that significantly stabilized DDK. Several inhibited DDK with comparable potency to PHA-767491, including Chk1 and PKR kinase inhibitors, but had divergent chemical scaffolds from known DDK inhibitors. Taken together, these data show that several well-known kinase inhibitors cross-react with DDK and also highlight the opportunity to design additional specific, biologically active DDK inhibitors for use as chemotherapeutic agents.

  11. The potent Cdc7-Dbf4 (DDK kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds.

    Directory of Open Access Journals (Sweden)

    Nanda Kumar Sasi

    Full Text Available Cdc7-Dbf4 kinase or DDK (Dbf4-dependent kinase is required to initiate DNA replication by phosphorylating and activating the replicative Mcm2-7 DNA helicase. DDK is overexpressed in many tumor cells and is an emerging chemotherapeutic target since DDK inhibition causes apoptosis of diverse cancer cell types but not of normal cells. PHA-767491 and XL413 are among a number of potent DDK inhibitors with low nanomolar IC50 values against the purified kinase. Although XL413 is highly selective for DDK, its activity has not been extensively characterized on cell lines. We measured anti-proliferative and apoptotic effects of XL413 on a panel of tumor cell lines compared to PHA-767491, whose activity is well characterized. Both compounds were effective biochemical DDK inhibitors but surprisingly, their activities in cell lines were highly divergent. Unlike PHA-767491, XL413 had significant anti-proliferative activity against only one of the ten cell lines tested. Since XL413 did not effectively inhibit DDK in multiple cell lines, this compound likely has limited bioavailability. To identify potential leads for additional DDK inhibitors, we also tested the cross-reactivity of ∼400 known kinase inhibitors against DDK using a DDK thermal stability shift assay (TSA. We identified 11 compounds that significantly stabilized DDK. Several inhibited DDK with comparable potency to PHA-767491, including Chk1 and PKR kinase inhibitors, but had divergent chemical scaffolds from known DDK inhibitors. Taken together, these data show that several well-known kinase inhibitors cross-react with DDK and also highlight the opportunity to design additional specific, biologically active DDK inhibitors for use as chemotherapeutic agents.

  12. 77 FR 5489 - Identification of Human Cell Lines Project

    Science.gov (United States)

    2012-02-03

    ... National Institute of Standards and Technology Identification of Human Cell Lines Project AGENCY: National... tandem repeat (STR) profiling up to 1500 human cell line samples as part of the Identification of Human Cell Lines Project. All data and corresponding information will be posted in a publically held...

  13. Retinoblastoma-independent antiproliferative activity of novel intracellular antibodies against the E7 oncoprotein in HPV 16-positive cells

    Directory of Open Access Journals (Sweden)

    Banks Lawrence

    2011-01-01

    Full Text Available Abstract Background "High risk" Human Papillomavirus strains are the causative agents of the vast majority of carcinomas of the uterine cervix. In these tumors, the physical integration of the HPV genome is a frequent, though not invariable occurrence, but the constitutive expression of the E6 and E7 viral genes is always observed, suggesting key roles for the E6 and E7 oncoproteins in the process of malignant transformation. The "intracellular antibody" technology using recombinant antibodies in single-chain format offers the possibility of targeting a protein in its intracellular environment even at the level of definite domains thus representing a valuable strategy to "knock out" the function of specific proteins. Methods In this study, we investigate the in vitro activity of two single-chain antibody fragments directed against the "high-risk" HPV 16 E7 oncoprotein, scFv 43M2 and scFv 51. These scFvs were expressed by retroviral system in different cell compartments of the HPV16-positive SiHa cells, and cell proliferation was analyzed by Colony Formation Assay and EZ4U assay. The binding of these scFvs to E7, and their possible interference with the interaction between E7 and its main target, the tumor suppressor pRb protein, were then investigated by immunoassays, PepSet™technology and Surface Plasmon Resonance. Results The expression of the two scFvs in the nucleus and the endoplasmic reticulum of SiHa cells resulted in the selective growth inhibition of these cells. Analysis of binding showed that both scFvs bind E7 via distinct but overlapping epitopes not corresponding to the pRb binding site. Nevertheless, the binding of scFv 43M2 to E7 was inhibited by pRb in a non-competitive manner. Conclusions Based on the overall results, the observed inhibition of HPV-positive SiHa cells proliferation could be ascribed to an interaction between scFv and E7, involving non-pRb targets. The study paves the way for the employment of specific sc

  14. Retinoblastoma-independent antiproliferative activity of novel intracellular antibodies against the E7 oncoprotein in HPV 16-positive cells

    International Nuclear Information System (INIS)

    'High risk' Human Papillomavirus strains are the causative agents of the vast majority of carcinomas of the uterine cervix. In these tumors, the physical integration of the HPV genome is a frequent, though not invariable occurrence, but the constitutive expression of the E6 and E7 viral genes is always observed, suggesting key roles for the E6 and E7 oncoproteins in the process of malignant transformation. The 'intracellular antibody' technology using recombinant antibodies in single-chain format offers the possibility of targeting a protein in its intracellular environment even at the level of definite domains thus representing a valuable strategy to 'knock out' the function of specific proteins. In this study, we investigate the in vitro activity of two single-chain antibody fragments directed against the 'high-risk' HPV 16 E7 oncoprotein, scFv 43M2 and scFv 51. These scFvs were expressed by retroviral system in different cell compartments of the HPV16-positive SiHa cells, and cell proliferation was analyzed by Colony Formation Assay and EZ4U assay. The binding of these scFvs to E7, and their possible interference with the interaction between E7 and its main target, the tumor suppressor pRb protein, were then investigated by immunoassays, PepSet™technology and Surface Plasmon Resonance. The expression of the two scFvs in the nucleus and the endoplasmic reticulum of SiHa cells resulted in the selective growth inhibition of these cells. Analysis of binding showed that both scFvs bind E7 via distinct but overlapping epitopes not corresponding to the pRb binding site. Nevertheless, the binding of scFv 43M2 to E7 was inhibited by pRb in a non-competitive manner. Based on the overall results, the observed inhibition of HPV-positive SiHa cells proliferation could be ascribed to an interaction between scFv and E7, involving non-pRb targets. The study paves the way for the employment of specific scFvs in immunotherapeutic

  15. Antiproliferative effects of γ-tocotrienol are associated with lipid raft disruption in HER2-positive human breast cancer cells.

    Science.gov (United States)

    Alawin, Osama A; Ahmed, Rayan A; Ibrahim, Baher A; Briski, Karen P; Sylvester, Paul W

    2016-01-01

    A large percentage of human breast cancers are characterized by excessive or aberrant HER2 activity. Lipid rafts are specialized microdomains within the plasma membrane that are required for HER2 activation and signal transduction. Since the anticancer activity of γ-tocotrienol is associated with suppression in HER2 signaling, studies were conducted to examine the effects of γ-tocotrienol on HER2 activation within the lipid raft microdomain in HER2-positive SKBR3 and BT474 human breast cancer cells. Treatment with 0-5μM γ-tocotrienol induced a significant dose-dependent inhibition in cancer cell growth after a 5-day culture period, and these growth inhibitory effects were associated with a reduction in HER2 dimerization and phosphorylation (activation). Phosphorylated HER2 was found to be primarily located in the lipid raft microdomain of the plasma membrane in vehicle-treated control groups, whereas γ-tocotrienol treatment significantly inhibited this effect. Assay of plasma membrane subcellular fractions showed that γ-tocotrienol also accumulates exclusively within the lipid raft microdomain. Hydroxypropyl-β-cyclodextrin (HPβCD) is an agent that disrupts lipid raft integrity. Acute exposure to 3mM HPβCD alone had no effect, whereas an acute 24-h exposure to 20μM γ-tocotrienol alone significantly decreased SKBR3 and BT474 cell viability. However, combined treatment with these agents greatly reduced γ-tocotrienol accumulation in the lipid raft microdomain and cytotoxicity. In summary, these findings demonstrate that the anticancer effects of γ-tocotrienol are associated with its accumulation in the lipid raft microdomain and subsequent interference with HER2 dimerization and activation in SKBR3 and BT474 human breast cancer cells.

  16. Cytotoxic and antiproliferative activity of Securidaca longepedunculata aqueous extract on Ehrlich ascites carcinoma cells in Swiss albino mice.

    OpenAIRE

    R A Lawal; M D Ozaslan; O S Odesanmi; I D Karagoz; I H Kilic; O AT Ebuehi

    2012-01-01

    Summary: Securidaca longepedunculata is a savannah shrub found growing in tropical Africa. It is reputed to have more than a hundred medicinal uses and is a major component of anticancer decoctions in Nigeria. An attempt was made in this study to determine the in vitro and in vivo cytotoxic activity and possible pro-apoptotic effect of Securidaca longepedunculata aqueous root bark extract on Ehrlich ascites carcinoma cells. In vitro cytotoxic activity was determined using the Trypan blue assa...

  17. Antiproliferative activity and phenotypic modification induced by selected Peruvian medicinal plants on human hepatocellular carcinoma Hep3B cells

    OpenAIRE

    Carraz, Maëlle; Lavergne, C.; Jullian, Valérie; Wright, M.; Gairin, J. E.; de la Cruz, M. G.; Bourdy, Geneviève

    2015-01-01

    Ethnopharmacological relevance: The high incidence of human hepatocellular carcinoma (HCC) in Peru and the wide use of medicinal plants in this country led us to study the activity against HCC cells in vitro of somes species used locally against liver and digestive disorders. Materials and methods: Ethnopharmacological survey: Medicinal plant species with a strong convergence of use for liver and digestive diseases were collected fresh in the wild or on markets, in two places of Peru: Chiclay...

  18. Trypsin Isoinhibitors with Antiproliferative Activity toward Leukemia Cells from Phaseolus vulgaris cv “White Cloud Bean”

    Directory of Open Access Journals (Sweden)

    Jian Sun

    2010-01-01

    Full Text Available A purification protocol that comprised ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75 was complied to isolate two trypsin inhibitors from Phaseolus vulgaris cv “White Cloud Bean”. Both trypsin inhibitors exhibited a molecular mass of 16 kDa and reduced the activity of trypsin with an IC50 value of about 0.6 M. Dithiothreitol attenuated the trypsin inhibitory activity, signifying that an intact disulfide bond is indispensable to the activity. [Methyl-3H] thymidine incorporation by leukemia L1210 cells was inhibited with an IC50 value of 28.8 M and 21.5 M, respectively. They were lacking in activity toward lymphoma MBL2 cells and inhibitory effect on HIV-1 reverse transcriptase and fungal growth when tested up to 100 M.

  19. Chloride transport in a glioma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Wolpaw, E.W.

    1984-01-01

    Maintenance of the extracellular environment is a major function of central nervous system astroglia. The transport of Cl/sup -/ across the cell membrane may be an integral part of this function, since Cl/sup -/ transport has been implicated in homeostasis of cell volume, pH, and extracellular K/sup +/ concentration. The work presented here investigated Cl/sup -/ transport in the glioma cell line LRM55. Results indicate that LRM55 cells are a good model for astroglia and that these cells contain three Cl/sup -/ transporters; a Cl/sup -//HCO/sub 3//sup -/ exchanger, a K/sup +//Cl/sup -/ cotransporter, and a Cl/sup -//SO/sub 4//sup 2 -/ exchanger. Ion transport studies measured the fluxes of Cl/sup -/ (as /sup 36/Cl/sup -/), K/sup +/ (as /sup 86/Rb/sup +/), and SO/sub 4//sup 2 -/ (as /sup 35/SO/sub 4//sup 2 -/). Cl/sup -/ flux was trans-simulated by Cl/sup -/ or HCO/sub 3//sup -/ and was inhibited by SITS or furosemide. External K/sup +/ stimulated Cl/sup -/ influx and external Cl/sup -/ stimulated Rb/sup +/ influx. Furosemide, but not SITS, inhibited the K/sup +//Cl/sup -/ cotransporter. High K/sup +/ medium increased cell volume and Cl/sup -/ content. Steady-state Cl/sup -/ concentration was at least twice that predicted from passive equilibration according to the Nernst equation. SO/sub 4//sup 2 -/ flux was trans-stimulated by SO/sub 4//sup 2 -/ or by Cl/sup -/. Cl/sup -/ was a competitive inhibitor of SO/sub 4//sup 2 -/ influx, but SO/sub 4//sup 2 -/ had no detectable effect on Cl/sup -/ influx or efflux. SO/sub 4//sup 2 -/ flux was inhibited by SITS or furosemide.

  20. Antiproliferative activity, antioxidant capacity and chemical composition of extracts from the leaves and stem of Chresta sphaerocephala

    Directory of Open Access Journals (Sweden)

    Larissa Saito da Costa

    2015-08-01

    Full Text Available AbstractIn this study, antiproliferative and antioxidant activities of crude extracts (hexane, ethyl acetate and methanol from leaves and stem of Chresta sphaerocephala DC., Asteraceae, were investigated. Antiproliferative activity was tested in vitro against ten human cancer cells and against VERO (no cancer cell. Antioxidant activities were determined using DPPH and ORAC-FL assays and the total phenolic content was estimated by Folin–Ciocalteu method. Hexane and ethyl acetate extracts (leaves and stem exhibited antiproliferative activity against cancer cell lines with total growth inhibition (TGI between 50.40 and 250 µg/ml. For VERO cell, TGI values were >250 µg/ml for all extracts, except to hexane extract of the stem (TGI 80.92 µg/ml. In an initial evaluation, ethyl acetate and methanol extracts (leaves and stem have shown levels of phenolic compounds between 6.94 and 30.96 mg GAE/kg in Folin–Ciocalteu assay, DPPH free-radical scavenging activity with SC50 in the range of 75.22 and 400 µg/ml and antioxidant capacity between 290.08 and 1088 µmol TE/g of extract in ORAC-FL assay. HPLC-DAD and ESI-MS analysis allowed the identification of flavonoids in the methanol extract from the leaves of C. sphaerocephala. Three steroids and nine triterpenoids were identified in the bioactive hexane extracts using HRGC.

  1. New naphthalene derivatives and isoquinoline alkaloids from Ancistrocladus cochinchinensis with their anti-proliferative activity on human cancer cells.

    Science.gov (United States)

    Lien, Le Quynh; Linh, Tran My; Giang, Vu Huong; Mai, Nguyen Chi; Nhiem, Nguyen Xuan; Tai, Bui Huu; Cuc, Nguyen Thi; Anh, Hoang Le Tuan; Ban, Ninh Khac; Minh, Chau Van; Kiem, Phan Van

    2016-08-15

    Five new compounds, named ancistronaphtosides A and B (1 and 2), anciscochine (3), anciscochine 6-O-β-d-glucopyranoside (4), and 4'-methoxy-5-epi-ancistecrorine A1 (5), together with tortoside A (6) and 4-hydroxy-2-methoxyphenyl-6-O-syringoyl-β-d-glucopyranoside (7) were isolated from the methanolic extract of Ancistrocladus cochinchinensis. Their chemical structures were established using HR-ESI-MS, NMR spectroscopic, and chiroptical methods. Compound 5 significantly exhibited anti-proliferation against HL-60, LU-1, and SK-MEL-2 cells with IC50 values of 5.0±1.2, 6.5±1.6, and 6.8±2.0μg/mL, respectively. PMID:27423477

  2. Design, Synthesis and Evaluation of Antiproliferative Activity of New Benzimidazolehydrazones

    Directory of Open Access Journals (Sweden)

    Valentina Onnis

    2016-04-01

    Full Text Available The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N′-(4-arylidene-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210, human T-cell leukemia (CEM, human cervix carcinoma (HeLa and human pancreas carcinoma cells (Mia Paca-2. A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC50 values in the low micromolar range.

  3. Ligation of the functional domain of complement receptor type 2 (CR2, CD21) is relevant for complex formation in T cell lines.

    Science.gov (United States)

    Prodinger, W M; Larcher, C; Schwendinger, M; Dierich, M P

    1996-04-01

    We investigated the potential of CD21, the complement receptor type 2, to form receptor complexes with other membrane molecules on T cell lines. CD21 from T cell lines transformed with human T cell leukemia virus type I (MT2, HUT-102, C5.MJ, Mondi, and C91.PL) and T cell lines that were not virus transformed was analyzed by coprecipitation following cell lysis with digitonin. mAbs binding to functional and nonfunctional epitopes of CD21 and a polyclonal antiserum against its intracellular portion precipitated CD21, which was indistinguishable from CD21 on B cell lines. In contrast to B cells, where CD21 is complexed with CD19 and CD81 (target of anti-proliferative Ab 1) or, alternatively, with CD35 (CR1), no surface molecules could be coprecipitated with three of four mAbs from these T cell lines. Therefore, we assume that CD21 is not part of a preformed complex in T cell lines. OKB7, the only mAb directed against the functional C3d binding site, coprecipitated two proteins of 105 and 55 Mr with CD21 from MT2 and Mondi cells and from the T cell lines Jurkat E6-1 and SupT1. These bands were also recovered with CD21 precipitated from MT2 cells with C3d bound to Sepharose via the internal thioester, but were absent in CD21-expressing B cell lines. As C3d and OKB7 are functional ligands for B cells, we propose that upon ligation on T cells, CD21 associates with molecules of 105/55 Mr in the plasma membrane. Whether this is the first event of a signal delivered to the T cell is under current investigation. PMID:8786322

  4. Recombinant Expression of a Novel Fungal Immunomodulatory Protein with Human Tumor Cell Antiproliferative Activity from Nectria haematococca

    Directory of Open Access Journals (Sweden)

    Shuying Li

    2014-09-01

    Full Text Available To our best knowledge, all of the fungal immunomodulatory proteins (FIPs have been successfully extracted and identified in Basidomycetes, with only the exception of FIP from ascomycete Nectria haematococca (FIP-nha discovered through homology alignment most recently. In this work, a gene encoding FIP-nha was synthesized and recombinantly expressed in an Escherichia coli expression system. SDS-PAGE and MALDI-MS analyses of recombinant FIP-nha (rFIP-nha indicated that the gene was successfully expressed. The yield of the bioactive FIP-nha protein was 42.7 mg/L. In vitro assays of biological activity indicated that the rFIP-nha caused hemagglutination of human and rabbit red blood cells, significantly stimulated mouse spleen lymphocyte proliferation, and enhanced expression of interleukin-2 (IL-2 released from mouse splenocytes, revealing a strong antitumor effect against HL60, HepG2 and MGC823. Through this work, we constructed a rapid and efficient method of FIP production, and suggested that FIP-nha is a valuable candidate for use in future medical care and pharmaceutical products.

  5. Rosa canina Extracts Have Antiproliferative and Antioxidant Effects on Caco-2 Human Colon Cancer

    Science.gov (United States)

    Jiménez, Sandra; Gascón, Sonia; Luquin, Asunción; Laguna, Mariano; Ancin-Azpilicueta, Carmen; Rodríguez-Yoldi, María Jesús

    2016-01-01

    The in vitro antiproliferative and antioxidant effects of different fractions of Rosa canina hips on human colon cancer cell lines (Caco-2) was studied. The compounds tested were total extract (fraction 1), vitamin C (fraction 2), neutral polyphenols (fraction 3) and acidic polyphenols (fraction 4). All the extracts showed high cytotoxicity after 72 h, both low and high concentrations. The flow cytometric analysis revealed that all the fractions produce disturbances in the cell cycle resulting in a concomitant cell death by an apoptotic pathway. Changes in the redox status of Caco-2 cells in response to Rosa canina hips were determined. Cells were exposed to hydrogen peroxide in presence of plant fractions and the production of Reactive Oxygen Species (ROS) was significantly decreased. Therefore, our data demonstrate that rosehip extracts are a powerful antioxidant that produces an antiproliferative effect in Caco-2 cells. Therefore, these results predict a promising future for Rosa canina as a therapeutic agent. Thus, this natural plant could be an effective component of functional foods addressed towards colorectal carcinoma. PMID:27467555

  6. Polyanionic Biopolymers for the Delivery of Pt(II Cationic Antiproliferative Complexes

    Directory of Open Access Journals (Sweden)

    Mauro Ravera

    2016-01-01

    Full Text Available Phenanthriplatin, that is, (SP-4-3-diamminechlorido(phenanthridineplatinum(II nitrate, an effective antitumor cationic Pt(II complex, was loaded on negatively charged dextran sulfate (DS as a model vector for drug delivery via electrostatic interactions. The free complex and the corresponding conjugate with DS were tested on two standard human tumor cell lines, namely, ovarian A2780 and colon HCT 116, and on several malignant pleural mesothelioma cell lines (namely, epithelioid BR95, mixed/biphasic MG06, sarcomatoid MM98, and sarcomatoid cisplatin-resistant MM98R. The in vitro results suggest that the conjugate releases the active metabolite phenanthriplatin with a biphasic fashion. In these experimental conditions, the conjugate is slightly less active than free phenanthriplatin; but both exhibited antiproliferative potency higher than the reference metallodrug cisplatin and were able to overcome the acquired cisplatin chemoresistance in MM98R cells.

  7. EXPRESSION OF Fas LIGAND IN HUMAN COLON CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    张建军; 丁尔迅; 王强; 陈学云; 付志仁

    2001-01-01

    To investigate the expression of Fas ligand in human colon carcinoma cell lines. Methods: A total of six human colon cancer cell lines were examined for the expression of Fas ligand mRNA and cell surface protein by using RT-PCR and flow cytometry respectively. Results: The results showed that Fas ligand mRNA was expressed in all of the six cancer cell lines and Fas ligand cell surface protein was expressed in part of them. Conclusion: These data suggest that Fas ligand was expressed, at least in part, in human colon cancer cell lines and might facilitate to escape from immune surveillance of the host.

  8. Antiproliferative Activities of Chemical Constituents Isolated from Thymus praecox subsp. grossheimii (Ronniger Jalas

    Directory of Open Access Journals (Sweden)

    Ramazan Erenler

    2016-05-01

    Full Text Available Thymus praecox subsp. grossheimii (Ronniger Jalas is (TPGJ an aromatic and medicinal plant used as folk medicine and exhibits a variety of biological activities. Aerial part of plant material was boiled in water then extracted with hexane and ethyl acetate sequentially. Flash column chromatography (Sephadex LH-20 and HPLC were used for ethy acetate extract to isolate rosmarinic acid (1, apigenin 7-O-glucoside (2, chrysoeriol (3, apigenin (4, naringenin (5 , eriodictiol (6, luteolin (7 and globoidnan A (8. The structures of isolated compounds were elucidated by spectroscopic techniques basically 1D, 2D-NMR and LC-TOF/MS/MS. Antiproliferative activity, cytotoxicity of compounds and extract were investigated in vitro on C6 (rat brain tumor, HeLa (human cervix carcinoma, HT29 (human colon carcinoma and Vero (African green monkey kidney epithelium cells lines by using BrdU cell proliferation ELISA and lactate dehydrogenase (LDH assays. Extract and some compounds exhibited significant antiproliferative effects against various cancerous cell lines.

  9. DNA profiling and characterization of animal cell lines.

    Science.gov (United States)

    Stacey, Glyn N; Byrne, Ed; Hawkins, J Ross

    2014-01-01

    The history of the culture of animal cell lines is littered with published and much unpublished experience with cell lines that have become switched, mislabelled, or cross-contaminated during laboratory handling. To deliver valid and good quality research and to avoid waste of time and resources on such rogue lines, it is vital to perform some kind of qualification for the provenance of cell lines used in research and particularly in the development of biomedical products. DNA profiling provides a valuable tool to compare different sources of the same cells and, where original material or tissue is available, to confirm the correct identity of a cell line. This chapter provides a review of some of the most useful techniques to test the identity of cells in the cell culture laboratory and gives methods which have been used in the authentication of cell lines. PMID:24297409

  10. Biological characteristics of cell lines of human dental alveolus

    Institute of Scientific and Technical Information of China (English)

    陈世璋; 黄靖香; 孙明学; 赵斌

    2003-01-01

    Objective To investigate the biological characteristics of cell lines of healthy and diseased human dental alveoli. Methods Primary cell lines from either healthy or diseased human dental alveoli were obtained. Two cell lines, H-258 and H-171 derived from healthy and diseased human tissues respectively, were selected for morphological study and research on their growth and aging, using cell counting, and histochemical and immunohistochemical staining. Results Primary cell lines were successfully established from innormal dental alveoli. After freezing and thawing for three times, cell growth was continued and no morphological alterations were observed. The doubling time was 53.4 hours and mean division index (MDI) was 4‰. Cells were kept normal after twenty generations with no obvious reduction of doubling time and MDI. Of twenty-six primary cell lines derived from healthy human dental alveoli, only three cell lines achieved generation. After freezing and thawing for twice, cultured cells were still alive at a decreased growth speed, with doubling time of 85.9 hours and MDI of 3‰. Both cell lines, H-171 and H-258, shared the characteristics of osteoblast. Conclusions Primary cell lines of diseased human dental alveoli show greater growth potential. All cell lines of dental alveoli share characteristics of osteoblast. The technique we developed may be put into practice for the treatment of abnormal dental alveoli.

  11. Identification of Target Genes Involved in the Antiproliferative Effect of Enzyme-Modified Ginseng Extract in HepG2 Hepatocarcinoma Cell

    OpenAIRE

    Sung-Il Jang; Yeon-Weol Lee; Chong-Kwan Cho; Hwa-Seung Yoo; Jun-Hyeog Jang

    2013-01-01

    Ginsenosides are ginseng saponins, which are the major biologically active components of Panax ginseng, often metabolized by intestinal bacteria into more effective forms. In this study, we found that the antiproliferative activity of ginseng increased after enzymatic processing of ginseng saponin (50% inhibitory concentration [IC50], >30  μ g/mL), which may be the result of the accumulation of minor saponins, such as Rh1, Rg3, compound K, and PPT constituents in ginseng saponin. Using the Ag...

  12. Cryptomoschatone D2 from Cryptocarya mandioccana: cytotoxicity against human cervical carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    CHRISTIANE PIENNA SOARES

    2010-06-01

    Full Text Available

    Among the substances isolated from Cryptocarya sp, some styrylpyrones, such as goniothalamin, demonstrate antiproliferative activity in a broad range of human cell lines. In the present study, we assessed the cytotoxicity of a styrylpyrone (cryptomoschatone D2, isolated from Cryptocarya mandiocanna, in HPV-infected (HeLa and SiHa and uninfected (C33A human cervical carcinoma cell lines and a human lung fibroblast line (MRC-5. The cytotoxicity was tested by the MTT assay. In this assay, cells were treated with cryptomoschatone D2 at 15, 30, 60 or 90 μM for 6, 24 or 48 hours, as well as for 6 hours followed by a post-treatment recovery period of 24, 48 or 72 hours. High cytotoxicity (dose- and timedependent was observed in HeLa, SiHa, C33A and MRC-5 cell lines. Although in general the styrylpyrone cytotoxicity was not significantly different among the cell lines tested, it was apparently stronger in HeLa and C33A than in MRC-5 and SiHa in the 24 or 48-hour treatments. Moreover, HeLa and SiHa were able to recover their ability to proliferate, in direct proportion to the post-treatment recovery time. On the other hand, C33A did not demonstrate a similar post-treatment recovery. We can conclude that cryptomoschatone D2 possesses high dose-dependent or time-dependent cytotoxicity. Keywords: Cell culture. Antiproliferative activity. Styrylpyrone, Cryptomoschatone D2. RESUMO Cryptomoscatona D2 de Cryptocarya mandioccana: atividade citotóxica contra linhagem celular de carcinoma cervical humano Dentre as substâncias isoladas de Cryptocarya sp, algumas estirilpironas, como a goniotalamina, apresentam atividade antiproliferativa em diferentes linhagens celulares. No presente estudo, foram avaliadas as atividades citotóxica de uma estirilpirona (criptomoscatona D2 isolada de Cryptocarya mandiocanna, em linhagens celulares de carcinoma cervical humano infectada por HPV (HeLa e SiHa, não infectada (C33A e fibroblasto pulmonar

  13. Antiproliferative and anti-inflammatory polyhydroxylated spirostanol saponins from Tupistra chinensis.

    Science.gov (United States)

    Xiang, Limin; Yi, Xiaomin; Wang, Yihai; He, Xiangjiu

    2016-01-01

    Tupistra chinensis is widely distributed in southwestern China and its rhizome is a famous folk medicine for the treatment of carbuncles and pharyngitis. Its chemical identity of potent antiproliferative and anti-inflammatory constituents has been carried out in this study. Twenty-three polyhydroxylated spirostanol saponins, including nine novels, were isolated and identified. The new spirostanol saponins were elucidated as spirost-25(27)-en-1β,2β,3β,4β,5β-pentol-2-O-β-D-xylopyranoside (1), spirost-25(27)- en-1β,2β,3β,4β,5β-pentol-2-O-α-L-arabinopyranoside (2), spirost-25(27)-en- 1β,3α,5β-triol (12), spirost-25(27)-en-1β,3α,4β,5β,6β-pentol (13), spirost-25(27)-en- 1β,2β,3β,5β-tetraol-5-O-β-D-glucopyranoside (16), 5β-spirost-25(27)-en-1β,3β-diol- 3-O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (17), (25R)-5β-spirostan- 1β,3β-diol-3-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (18), (25R)-5β- spirostan-1β,3β-diol-3-O-β-D-fructofuranosyl-(2 → 6)-β-D-glucopyranoside (19), 5β-spirost-25(27)-en-3β-ol-3-O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (20). The antiproliferative effects against seven human cancer cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7 were assayed for all the isolated compounds. Compounds 17, 19 and 21 exhibited potential antiproliferative activities against all of human cancer cell lines tested. Compounds 21 showed significant inhibition on NO production with IC50 values of 11.5 μM. These results showed that the spirostanol saponins isolated from the dried rhizomes of T. chinensis have potent antiproliferative and anti-inflammatory activities and T. chinensis might be used as anticancer and.anti-inflammatory supplement. PMID:27530890

  14. Novel combination of sorafenib and celecoxib provides synergistic anti-proliferative and pro-apoptotic effects in human liver cancer cells.

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    Melchiorre Cervello

    Full Text Available Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC. Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex® is a selective cyclooxygenase-2 (COX-2 inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies.

  15. Cloning of aminopeptidase Npromoter and its activity in hematopoietic cell and different tumor cell lines

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Aminopeptidase N (APN) promoter region was cloned and sequenced from peripheral blood mononuclear cells. The recombinant reporter construct containing the promoter and luciferase gene, designated pXP1-APNLuc, was introduced into myeloblastic cell line, T lymphocyte cell line and various tumor cell lines. Luciferase assay showed that APN upstream promoter is myeloid-specific for high expression in myeloblastic cell line and much lower expres sion in T lymphocyte cell line. The promoter activity was relatively high in lung adenoma cell line compared with other tumor cell lines including hepatoma cell line, tong cancer cell line and esophageal cancer cell line in which the promoter activity significantly diminished or was almost undetectable. The characteristics of APN promoter may pro vide a new strategy for specific myeloprotection while tumor patients are being treated with chemotherapy and/or radio therapy.

  16. L-carvone induces p53, caspase 3 mediated apoptosis and inhibits the migration of breast cancer cell lines.

    Science.gov (United States)

    Patel, Pinaki B; Thakkar, Vasudev R

    2014-01-01

    A wide variety of natural compounds exists that possesses significant cytotoxic as well as chemopreventive activity through induction of apoptosis in cancer cells. The antiproliferative and apoptotic effect of L-carvone, an active component of spearmint (Mentha spicata) was studied on breast cancer (MCF 7 and MDA MB 231) and normal (MCF 10A) cell lines, and insight into its mechanism of action was attained. L-carvone inhibited proliferation of MCF 7 (IC50 1.2 mM) and MDA MB 231 cells (IC50 1.0 mM) and inhibited the migration of breast cancer cell lines. L-carvone induced apoptosis as observed by nuclei fragmentation and the presence of apoptotic bodies in DAPI, AnnexinV/propidium iodide, and TUNEL assays. L-carvone exposure arrested MCF 7 cells in S phase of the cell cycle. DNA damage caused by L-carvone was apparent from the increased tail moment in COMET assay, which could be induced by an increase in ROS that was measured using a fluorescence probe. Glutathione levels were also increased. The increased level of p53, Bad, cleaved caspase 3, and cleaved PARP explained p53 and caspase-mediated apoptosis. PMID:24611509

  17. Antiproliferative, DNA cleavage, and ADMET study of substituted 2-(1-benzofuran-2-yl quinoline-4-carboxylic acid and its esters

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    R. Anantacharya

    2016-12-01

    Full Text Available Synthesis, anti-proliferative, DNA cleavage, and in silico ADMET studies of 2-(1-benzofuran-2-yl quinoline-4-carboxylic acids and their resultant esters in acid catalyzed medium have been investigated. The synthesized compounds are characterized by UV, IR, 1H NMR, 13C NMR, and mass spectral analysis. The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest using agarose gel method and the antiproliferative activity was carried out by MTT assay on five different human cancer cell lines (Chronic Myelogenous Leukemia (K562, Breast Cancer (MCF-7, Cervical Cancer (HeLa, Colorectal Adino carcinoma (Colo 205, and Hepato cellular carcinoma (HepG2. Doxorubicin is taken as standard for comparison. The cleavage study indicated that molecules (3b–6a and 7b–8c did cleave the DNA completely with no trace of fragments. The molecules (6b, 6c and 7a have appeared to cleave DNA partially and assessed by comparing the bands appeared in control and test compounds at 100 μg concentration. The MTT antiproliferative activity of the synthesized derivatives at a concentration of 10 mM screened that out of the five cancer cell lines tested, the compounds 8b (25.97%, MCF-7, 7a (25.36%, Colo 205, and 7b (24.22%, HePG showed considerable degree of activity at a very low concentration. The molecules were active against MCF-7, Colo 205, and HepG. The molecules exhibited acceptable range in in silico ADMET prediction, significant DNA cleavage, and antiproliferative properties. The study further provides identification of possible lead moiety as an antiproliferative agent.

  18. Antiproliferative and cancer-chemopreventive properties of sulfated glycosylated extract derived from Leucaena leucocephala

    Directory of Open Access Journals (Sweden)

    Gamal-Eldeen Amira

    2007-01-01

    Full Text Available This work aimed to prove that simple chemical modification could provide new cancer chemopreventive and/or anticancer properties to the inactive extracted polysaccharide derived from Leucaena leucocephala . Polysaccharides were extracted from Leucaena leucocephala seeds and its 2,4-pentanedione-treated derivative (glycosylated form was prepared, which is further sulphated to give sulphated glycosylated form. Estimation of their anti-initiation activity, modulation of carcinogen metabolism, was indicated by the inhibition cytochrome P450 1A (CYP1A and the induction of glutathione-S-transferases (GSTs. Anti-proliferation activity was investigated by MTT assay against human hepatocarcinoma (HepG2, breast carcinoma (MCF-7 and lymphoblastic leukemia (1301. Apoptosis/necrosis and cell cycle were analyzed by flow cytometry. The results revealed that glycosylated form inhibited both CYP1A and GSTs, while sulphated glycosylated form not only inhibited CYP1A, but also induced the GSTs. Unlike GE, sulphated glycosylated form possessed a significant anti-proliferative activity against different cell lines. Analysis of HepG2 cell cycle phases demonstrated that glycosylated form led to a delay of G2/M-phase, while sulphated glycosylated form led to a concomitant arrest in S- and G2/M-phases. Investigation of apoptosis/necrosis ratio demonstrated that both of glycosylated form and sulphated glycosylated form induced HepG2 cell death by necrosis, but not apoptosis. Unmodified crude extract was neither active as cancer chemopreventive nor as anti-proliferative. In conclusion, chemical modification of Leucaena gum induced its cancer chemopreventive and anti-proliferative activities.

  19. Development and characterization of a new human hepatic cell line

    Science.gov (United States)

    Ramboer, Eva; De Craene, Bram; De Kock, Joey; Berx, Geert; Rogiers, Vera; Vanhaecke, Tamara; Vinken, Mathieu

    2015-01-01

    The increasing demand and hampered use of primary human hepatocytes for research purposes have urged scientists to search for alternative cell sources, such as immortalized hepatic cell lines. The aim of this study was to develop a human hepatic cell line using the combined overexpression of TERT and the cell cycle regulators cyclin D1 and mutant isoform CDK4R24C. Following transduction of adult human primary hepatocytes with the selected immortalization genes, cell growth was triggered and a cell line was established. When cultured under appropriate conditions, the cell line expressed several hepatocytic markers and liver-enriched transcription factors at the transcriptional and/or translational level, secreted liver-specific proteins and showed glycogen deposition. These results suggest that the immortalization strategy applied to primary human hepatocytes could generate a novel hepatic cell line that seems to retain some key hepatic characteristics. PMID:26869867

  20. Salivary α-amylase exhibits antiproliferative effects in primary cell cultures of rat mammary epithelial cells and human breast cancer cells

    OpenAIRE

    Bertram Catharina; Hass Ralf; Fedrowitz Maren; Löscher Wolfgang

    2011-01-01

    Abstract Background Breast cancer is one of the most diagnosed cancers in females, frequently with fatal outcome, so that new strategies for modulating cell proliferation in the mammary tissue are urgently needed. There is some, as yet inconclusive evidence that α-amylase may constitute a novel candidate for affecting cellular growth. Methods The present investigation aimed to examine if salivary α-amylase, an enzyme well known for the metabolism of starch and recently introduced as a stress ...

  1. MODERATE CYTOTOXICITY OF PROANTHOCYANIDINS TO HUMAN TUMOR-CELL LINES

    NARCIS (Netherlands)

    KOLODZIEJ, H; HABERLAND, C; WOERDENBAG, HJ; KONINGS, AWT

    1995-01-01

    In the present study the cytotoxicity of 16 proanthocyanidins was evaluated in GLC(4), a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. With IC50 values ranging from 18 to >200 mu m following continuous

  2. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients

    International Nuclear Information System (INIS)

    Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown. We assessed immune cells infiltrate (CD56, CD68, CD3, CD4, CD8, Foxp3) in the primary tumor of metastatic colorectal cancer (mCRC) patients treated with a first-line cetuximab-based chemotherapy in the framework of prospective trials (treatment group) and in a matched group of mCRC patients who received the same chemotherapy regimen without cetuximab (control group). The relationship between intra-tumoral immune effector cells, the K-ras status and the efficacy of the treatment were investigated. We also evaluated in vitro, the ADCC activity in healthy donors and chemonaive mCRC patients and the specific contribution of CD56+ cells. ADCC activity against DLD1 CRC cell line is maintained in cancer patients and significantly declined after CD56+ cells depletion. In multivariate analysis, K-ras wild-type (HR: 4.7 (95% CI 1.8-12.3), p = 0.001) and tumor infiltrating CD56+ cells (HR: 2.6, (95%CI:1.14-6.0), p = 0.019) were independent favourable prognostic factors for PFS and response only in the cetuximab treatment group. By contrast CD56+ cells failed to predict PFS and response in the control group. CD56+ cells, mainly NK cells, may be the major effector of ADCC related-cetuximab activity. Assessment of CD56+ cells infiltrate in primary colorectal adenocarcinoma may provide additional information to K-ras status in predicting response and PFS in mCRC patients treated with first-line cetuximab-based chemotherapy

  3. Distinct differentiation characteristics of individual human embryonic stem cell lines

    Directory of Open Access Journals (Sweden)

    Knuutila Sakari

    2006-08-01

    Full Text Available Abstract Background Individual differences between human embryonic stem cell (hESC lines are poorly understood. Here, we describe the derivation of five hESC lines (called FES 21, 22, 29, 30 and 61 from frozen-thawed human embryos and compare their individual differentiation characteristic. Results The cell lines were cultured either on human or mouse feeder cells. The cells grew significantly faster and could be passaged enzymatically only on mouse feeders. However, this was found to lead to chromosomal instability after prolonged culture. All hESC lines expressed the established markers of pluripotent cells as well as several primordial germ cell (PGC marker genes in a uniform manner. However, the cell lines showed distinct features in their spontaneous differentiation patterns. The embryoid body (EB formation frequency of FES 30 cell line was significantly lower than that of other lines and cells within the EBs differentiated less readily. Likewise, teratomas derived from FES 30 cells were constantly cystic and showed only minor solid tissue formation with a monotonous differentiation pattern as compared with the other lines. Conclusion hESC lines may differ substantially in their differentiation properties although they appear similar in the undifferentiated state.

  4. Ficus carica latex prevents invasion through induction of let-7d expression in GBM cell lines.

    Science.gov (United States)

    Tezcan, Gulcin; Tunca, Berrin; Bekar, Ahmet; Yalcin, Murat; Sahin, Saliha; Budak, Ferah; Cecener, Gulsah; Egeli, Unal; Demir, Cevdet; Guvenc, Gokcen; Yilmaz, Gozde; Erkan, Leman Gizem; Malyer, Hulusi; Taskapilioglu, Mevlut Ozgur; Evrensel, Turkkan; Bilir, Ayhan

    2015-03-01

    Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs and dietary plants has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Ficus carica (fig) latex (FCL) has been determined in a few cancer types, the effect of this latex on GBM tumors has not been investigated. Therefore, in the current study, the anti-proliferative activity of FCL and the effect of the FCL-temozolomide (TMZ) combination were tested in the T98G, U-138 MG, and U-87 MG GBM cell lines using the WST-1 assay. The mechanism of cell death was analyzed using Annexin-V/FITC and TUNEL assays, and the effect of FCL on invasion was tested using the chick chorioallantoic membrane assay. To determine the effect of FCL on GBM progression, the expression levels of 40 GBM associated miRNAs were analyzed in T98G cells using RT-qPCR. According to the obtained data, FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergistically increased in combination with TMZ. In addition, the current study is the first to demonstrate the effect of FCL on modulation of let-7d expression, which may be an important underlying mechanism of the anti-invasive effect of this extract. PMID:25212824

  5. Chemical constituents isolated from the bark of Guatteria blepharophylla (Annonaceae) and their antiproliferative and antimicrobial activities

    International Nuclear Information System (INIS)

    Phytochemical study of the bark of Guatteria blepharophylla (Mart.) Mart. afforded twelve compounds, namely two sesquiterpenes, caryophyllene oxide (1) and spathulenol (3), one xanthone, lichexanthone (2), a mixture of steroids, b-sitosterol (4), and stigmasterol (5), and seven isoquinoline alkaloids, O-methylmoschatoline (6), lysicamine (7), nornuciferine (8), liriodenine (9), isocoreximine (10), subsessiline (11), and isomoschatoline (12). Their structures were established on the basis of spectroscopic methods. Compounds 1-6, 11 and 12 were reported for the first time in this species. The 13C NMR (nuclear magnetic resonance) data for the compounds 11 and 12 are described for the first time in the literature. The antiproliferative activity against human tumour cell lines and antimicrobial activities were investigated for the major compounds. Compound 9 showed significant activity against cell lines of breast (MCF-7, Michigan Cancer Foundation-7), superior to the positive control doxorubicin. Compound 12 presented antifungal activity similar to the positive control nystatin against Candida albicans. (author)

  6. Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents.

    Directory of Open Access Journals (Sweden)

    Anna Gliszczyńska

    Full Text Available The synthesis of novel phosphatidylcholines with geranic and citronellic acids in sn-1 and sn-2 positions is described. The structured phospholipids were obtained in high yields (59-87% and evaluated in vitro for their cytotoxic activity against several cancer cell lines of different origin: MV4-11, A-549, MCF-7, LOVO, LOVO/DX, HepG2 and also towards non-cancer cell line BALB/3T3 (normal mice fibroblasts. The phosphatidylcholines modified with monoterpene acid showed a significantly higher antiproliferative activity than free monoterpene acids. The highest activity was observed for the terpene-phospholipids containing the isoprenoid acids in sn-1 position of phosphatidylcholine and palmitic acid in sn-2.

  7. Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents

    Science.gov (United States)

    Gliszczyńska, Anna; Niezgoda, Natalia; Gładkowski, Witold; Czarnecka, Marta; Świtalska, Marta; Wietrzyk, Joanna

    2016-01-01

    The synthesis of novel phosphatidylcholines with geranic and citronellic acids in sn-1 and sn-2 positions is described. The structured phospholipids were obtained in high yields (59–87%) and evaluated in vitro for their cytotoxic activity against several cancer cell lines of different origin: MV4-11, A-549, MCF-7, LOVO, LOVO/DX, HepG2 and also towards non-cancer cell line BALB/3T3 (normal mice fibroblasts). The phosphatidylcholines modified with monoterpene acid showed a significantly higher antiproliferative activity than free monoterpene acids. The highest activity was observed for the terpene-phospholipids containing the isoprenoid acids in sn-1 position of phosphatidylcholine and palmitic acid in sn-2. PMID:27310666

  8. Chemical constituents isolated from the bark of Guatteria blepharophylla (Annonaceae) and their antiproliferative and antimicrobial activities

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Emmanoel V.; Marques, Francisco de Assis; Maia, Beatriz H.L.N.S., E-mail: noronha@ufpr.b [Universidade Federal do Parana (DQ/UFPR), Curitiba, PR (Brazil). Dept. de Quimica; Pinheiro, Maria Lucia B. [Universidade Federal do Amazonas (DQ/UFAM), Manaus, AM (Brazil). Dept. de Quimica; Braga, Raquel M. [Universidade Estadual de Campinas (IQ/UNICAMP), SP (Brazil). Inst. de Quimica; Delarmelina, Camila; Duarte, Marta Cristina T.; Ruiz, Ana Lucia T.G.; Carvalho, Joao Ernesto de [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Div. de Microbiologia e Div. Farmacologia e Toxicologia

    2011-07-01

    Phytochemical study of the bark of Guatteria blepharophylla (Mart.) Mart. afforded twelve compounds, namely two sesquiterpenes, caryophyllene oxide (1) and spathulenol (3), one xanthone, lichexanthone (2), a mixture of steroids, b-sitosterol (4), and stigmasterol (5), and seven isoquinoline alkaloids, O-methylmoschatoline (6), lysicamine (7), nornuciferine (8), liriodenine (9), isocoreximine (10), subsessiline (11), and isomoschatoline (12). Their structures were established on the basis of spectroscopic methods. Compounds 1-6, 11 and 12 were reported for the first time in this species. The {sup 13}C NMR (nuclear magnetic resonance) data for the compounds 11 and 12 are described for the first time in the literature. The antiproliferative activity against human tumour cell lines and antimicrobial activities were investigated for the major compounds. Compound 9 showed significant activity against cell lines of breast (MCF-7, Michigan Cancer Foundation-7), superior to the positive control doxorubicin. Compound 12 presented antifungal activity similar to the positive control nystatin against Candida albicans. (author)

  9. Design, Synthesis and Antiproliferative Activity of Novel Benzothiazole Derivatives Conjugated with Semicarbazone Scaffold.

    Science.gov (United States)

    Bao, Guanglong; Du, Baoquan; Ma, Yuxiu; Zhao, Meng; Gong, Ping; Zhai, Xin

    2016-01-01

    Two series of novel benzothiazole derivatives conjugated with semicarbazone scaffold were designed and synthesized through a structure-based molecular hybridization strategy. All the target compounds were evaluated for their cytotoxicity in vitro against three cancer cell lines (HT-29, MKN-45 and H460) by standard MTT assay. The pharmacological results indicated that seven compounds (17h-n) exhibited comparable or even better antiproliferative activity in comparison with reference drugs Sorafenib and PAC-1. Particularly, compound 17i displayed remarkable cytotoxicity against tested three cancer cell lines with IC50 values of 0.84, 0.06 and 0.52 µM, which were 4.3-, 36.6-, 4.2-folds more potent than Sorafenib and 1.2-, 13.7-, 6.9-times more active than PAC-1, respectively. PMID:26740207

  10. Cytotoxicity, Antiproliferative Effects, and Apoptosis Induction of Methanolic Extract of Cynometra cauliflora Linn. Whole Fruit on Human Promyelocytic Leukemia HL-60 Cells

    Directory of Open Access Journals (Sweden)

    T-Johari S. A. Tajudin

    2012-01-01

    Full Text Available Methanolic extract of Cynometra cauliflora whole fruit was assayed for cytotoxicity against the human promyelocytic leukemia HL-60 and the normal mouse fibroblast NIH/3T3 cell lines by using the MTT assay. The CD50 of the extract for 72 hours was 0.9 μg/mL whereas the value for the cytotoxic drug vincristine was 0.2 μg/mL. The viability of the NIH/3T3 cells was at 80.0% when treated at 15.0 μg/mL. The extract inhibited HL-60 cell proliferation with dose dependence. AO/PI staining of HL-60 cells treated with the extract revealed that majority of cells were in the apoptotic cell death mode. Flow cytometry analysis of HL-60 cells treated at CD50 of the extract showed that the early apoptotic cells were 31.0, 26.3 and 19.9% at 24, 48, and 72 hours treatment, respectively. The percentage of late apoptotic cells was increased from 62.0 at 24 hours to 64.1 and 70.2 at 48 and 72 hours, respectively. Meanwhile, percent of necrotic cells were 4.9, 6.6, and 8.5 at 24, 48, and 72 hours, respectively. This study has shown that the methanolic extract of C. cauliflora whole fruit was cytotoxic towards HL-60 cells and induced the cells into apoptotic cell death mode, but less cytotoxic towards NIH/3T3 cells.

  11. Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H-quino[3,4-b][1,4]benzothiazine Derivatives

    Directory of Open Access Journals (Sweden)

    Andrzej Zięba

    2016-11-01

    Full Text Available A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines. Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53, apoptosis (BAX, BCL-2, as well as proliferation (H3 were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide.

  12. Analysis of three marine fish cell lines by rapd assay.

    Science.gov (United States)

    Guo, H R; Zhang, S C; Tong, S L; Xiang, J H

    2001-01-01

    We tested the applicability of the random amplified polymorphic deoxyribonucleic acid (RAPD) analysis for identification of three marine fish cell lines FG, SPH, and RSBF, and as a possible tool to detect cross-contamination. Sixty commercial 10-mer RAPD primers were tested on the cell lines and on samples collected from individual fish. The results obtained showed that the cell lines could be identified to the correspondent species on the basis of identical patterns produced by 35-48% of the primers tested; the total mean similarity indices for cell lines versus correspondent species of individual fish ranged from 0.825 to 0.851, indicating the existence of genetic variation in these cell lines in relation to the species of their origin. Also, four primers, which gave a monomorphic band pattern within species/line, but different among the species/line, were obtained. These primers can be useful for identification of these cell lines and for characterization of the genetic variation of these cell lines in relation to the species of their origin. This supported the use of RAPD analysis as an effective tool in species identification and cross-contamination test among different cell lines. PMID:11573817

  13. Evaluation of Abelmoschus moschatus extracts for antioxidant, free radical scavenging, antimicrobial and antiproliferative activities using in vitro assays

    Directory of Open Access Journals (Sweden)

    Qureshi Insaf A

    2011-08-01

    Full Text Available Abstract Background Abelmoschus moschatus Medik. leaves and seeds are considered as valuable traditional medicine. The aromatic seeds of this plant are aphrodisiac, ophthalmic, cardio tonic, antispasmodic and used in the treatment of intestinal complaints and check queasiness. To give a scientific basis for traditional usage of this medicinal plant, the seed and leaf extracts were evaluated for their antioxidant, free radical scavenging, antimicrobial and antiproliferative activities. Methods In this study, antioxidant, antimicrobial and antiproliferative activities of A. moschatus extracts were evaluated in a series of in vitro assay involving free radicals, reactive oxygen species and their IC50 values were also determined. The antioxidant activities of the seed and leaf extracts of A. moschatus were determined by total antioxidant, DPPH, and ferrous reducing antioxidant property (FRAP methods. In addition, the antiproliferative activity was also evaluated using colorectal adenocarcinoma and retinoblastoma human cancer cell lines. Moreover, six bacterial reference strains, two gram-positive (Bacillus subtilis and Staphylococcus aureus, four gram-negative (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Salmonella enterica paratyphi and one fungal strain (Candida albicans were used to evaluate its antimicrobial activity. Results The results from this study showed that the antioxidant activities of A. moschatus as determined by the total phenol, flavonoids, total antioxidant and FRAP methods were higher in leaf than that of the seed extracts. On the other hand, the aqueous overnight seed extract (AMS-I has shown significant radical scavenging activity as in 1, 1- Diphenyl-2-picrylhydrazyl (DPPH, hydrogen peroxide, hydroxyl radical, superoxide and lipid peroxidation as compared to other seed and leaf extracts. The AMS-I and AML-IV have shown activity against six and seven microorganisms respectively. Simulteneously, AMS-IV and AML

  14. [Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

    Science.gov (United States)

    Gao, Liu-zhou; Xie, Yu-suo; Yan, Qiang; Wu, Shu-min; Ni, Li-li; Zhao, Hui; Huang, Wen-long; Hu, Guo-qiang

    2015-08-01

    To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues. PMID:26669001

  15. A biochemical and cellular approach to explore the antiproliferative and prodifferentiative activity of Aloe arborescens leaf extract.

    Science.gov (United States)

    Di Luccia, Blanda; Manzo, Nicola; Vivo, Maria; Galano, Eugenio; Amoresano, Angela; Crescenzi, Elvira; Pollice, Alessandra; Tudisco, Raffaella; Infascelli, Federico; Calabrò, Viola

    2013-12-01

    Aloe arborescens Miller, belonging to the Aloe genus (Liliaceae family), is one of the main varieties of Aloe used worldwide. Although less characterized than the commonest Aloe vera, Aloe arborescens is known to be richer in beneficial phytotherapeutic, anticancer, and radio-protective properties. It is commonly used as a pharmaceutical ingredient for its effect in burn treatment and ability to increase skin wound healing properties. However, very few studies have addressed the biological effects of Aloe at molecular level. The aim of the research is to provide evidences for the antiproliferative properties of Aloe arborescens crude leaf extract using an integrated proteomic and cellular biological approach. We analysed the composition of an Aloe arborescens leaf extract by gas chromatography-mass spectrometry analysis. We found it rich in Aloe-emodin, a hydroxylanthraquinone with known antitumoral activity and in several compounds with anti-oxidant properties. Accordingly, we show that the Aloe extract has antiproliferative effects on several human transformed cell lines and exhibits prodifferentiative effects on both primary and immortalized human keratinocyte. Proteomic analysis of whole cell extracts revealed the presence of proteins with a strong antiproliferative and antimicrobial activity specifically induced in human keratinocytes by Aloe treatment supporting its application as a therapeutical agent. PMID:23418125

  16. Crude extracts of marine-derived and soil fungi of the genus Neosartorya exhibit selective anticancer activity by inducing cell death in colon, breast and skin cancer cell lines

    Directory of Open Access Journals (Sweden)

    Alice Abreu Ramos

    2016-01-01

    Full Text Available Background: The crude ethyl acetate extracts of marine-derived fungi Neosartorya tsunodae KUFC 9213 (E1 and N. laciniosa KUFC 7896 (E2, and soil fungus N. fischeri KUFC 6344 (E3 were evaluated for their in vitro anticancer activities on a panel of seven human cancer cell lines. Materials and Methods: The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay was performed, after 48 h treatments with different concentrations of extracts, to determine their concentration of the extract or Dox that inhibits cell viability by 50% for each cell line. The effects of the crude extracts on DNA damage, clonogenic potential and their ability to induce cell death were also assessed. Results: E1 was found to the void of anti-proliferative effects. E2 was shown to decrease the clonogenic potential in human colorectal carcinoma cell line (HCT116, human malignant melanoma cell line (A375, human breast adenocarcinoma cell line (MCF7, and human caucasian colon adenocarcinoma Grade II cell line (HT29 cells, whereas E3 showed such effect only in HCT116 and MCF7 cells. Both extracts were found to increase DNA damage in some cell lines. E2 was found to induce cell death in HT29, HCT116, MCF7, and A375 cells while extract E3 increased cell death in MCF7 and HCT116 cell lines. Conclusion: The results reveal that E2 and E3 possess anticancer activities in human colon carcinoma, breast adenocarcinoma, and melanoma cells, validating the interest for an identification of molecular targets involved in the anticancer activity.

  17. POTENTIAL CELL LINE TOXICITY OF ENVIRONMENTAL NANOPARTICLES

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    Mohan Durga

    2012-01-01

    Full Text Available In India, the unprecedented growth rate and urbanization along with the rapid increase in motor vehicle activity and industrialization are contributing to high levels of urban air pollution. The population is mainly exposed to high air pollution concentrations, where motor vehicle emissions constitute the main source of fine and ultrafine particles. Motor exhaust emissions is a mixture of gases and Particulate Matter (PM. Diesel and petrol fuels in vehicles produce combustion-derived particles as a result of combustion. Vehicle exhaust particles are the main constituents of environmental nanoparticles. In the present investigation, environmental nanoparticles such as Diesel Exhaust Particles (DEP and Petrol Exhaust Particles (PEP were collected from on-road vehicles using a specially designed collection chamber. The surface morphology of the collected particles was analyzed through Transmission Electron Microscope (TEM, and the elemental mapping was performed through EDAX analysis. Results indicated the presence of nanometer-size particles in both the categories of vehicle exhaust. These small-size particles of respirable range can enter the respiratory tract of humans and get deposited in the lungs and cause various effects inside the human body. The aim of this study is to assess the cytotoxicity of the collected Diesel Exhaust Nanoparticles (DENPs and Petrol Exhaust Nanoparticles (PENPs. Cytotoxicity endpoint, such as IC50 (50% Inhibitory Concentration, was determined after a 24-h exposure. Results of this study indicated that all five cell lines were sensitive to these vehicle exhaust nanoparticles at varying levels.

  18. Antiproliferative Potential of Officinal Forms and Nanoparticles of Lithium Salts.

    Science.gov (United States)

    Lykov, A P; Poveshchenko, O V; Bondarenko, N A; Bogatova, N P; Makarova, O P; Konenkov, V I

    2016-04-01

    We studied the effect of officinal forms and nanoparticles of lithium carbonate and lithium citrate on proliferative activity of hepatoma-29 cells. Lithium carbonate nanoparticles suppressed proliferation of hepatoma-29 cells in lower concentrations than officinal form of this salt. The antiproliferative effect of lithium salts i activation of apoptosis and arrest of hepatoma-29 cells in the G2/M phase of the cell cycle. PMID:27165073

  19. Synthesis and Biological Evaluation of Apigenin Derivatives as Antibacterial and Antiproliferative Agents

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    Jinyi Wang

    2013-09-01

    Full Text Available Two series of apigenin [5,7-dihydroxy-2-(4-hydroxyphenyl-4H-chromen-4-one] derivatives, 3a–3j and 4a–4j, were synthesized. The apigenin and alkyl amines moieties of these compounds were separated by C2 or C3 spacers, respectively. The chemical structures of the apigenin derivatives were confirmed using 1H-NMR, 13C-NMR, and electrospray ionization mass spectroscopy. The in vitro antibacterial and antiproliferative activities of all synthesized compounds were determined. Among the tested compounds, 4a–4j displayed significant antibacterial activity against the tested strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. Additionally, 4i showed the best inhibitory activity with minimum inhibitory concentrations of 1.95, 3.91, 3.91, and 3.91 μg/mL against S. aureus, B. subtilis, E. coli, and P. aeruginosa, respectively. The antiproliferative activity of the apigenin derivatives was evaluated by an MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide] assay. We determined that 4a–4j displayed better growth inhibition activity against four human cancer cell lines, namely, human lung (A549, human cervical (HeLa, human hepatocellular liver (HepG2, and human breast (MCF-7 cancer cells, than the parent apigenin. Compound 4j was found to be the most active antiproliferative compound against the selected cancer cells. Structure-activity relationships were also discussed based on the obtained experimental data.

  20. In vitro anti-proliferative, anti-bacterial potential and induction of DNA strand break of partially purified Cuscuta reflexa Roxb.

    Directory of Open Access Journals (Sweden)

    Madhulika Bhagat

    2011-01-01

    Full Text Available Cuscuta reflexa is an important medicinal plant, mentioned in Ayurveda, an ancient Indian system of medicine. The plant is selected to evaluate the possibility for novel pharmaceuticals for anticancer and antibiotics drugs. Since most of these drugs had developed resisitance against currently used chemotherapeutics. This study describes the in vitro anti-proliferative, anti-bacterial and single stand DNA break of the holoprasitic plant Cuscuta reflexa. Bioassay-guided fractionation and partial purification of the plant were done and evaluated for antiproliferative activity against human cancer cell lines by SRB assay and single strand DNA break by comet assay. Further antibacterial activity was also performed by agar well diffusion assay. The alcoholic extract, chloroform fraction and partially purified ethylacetate-methanol (1:1 sub-fraction of C. reflexa showed anti-proliferative potential against IMR-32 and 502713 human cancer cell lines. Alcoholic extract exhibited anti-proliferative activity of 74% and 72%, chloroform fraction demonstrated 91% and 95% against neuroblastoma (IMR-32 and colon (502713 cancer cell lines at 100 μg/ml. Single strand DNA break of the chloroform fraction was also demonstrated using comet assay, indicating that possible mode of cell death may be apoptosis. Anti-microbial properties were evaluated against eight species of pathogenic and non-pathogenic microorganisms and maximum zone of inhibition for anti-bacterial activity was found against Staphylococcus aureus (22 mm by alcoholic extract, 21 mm by chloroform fraction and 12 mm by ethylacetate-methanol (1:1 sub-fraction. Minimum inhibitory concentration (MIC of the chloroform fraction was 1500 μg/ml for S. aureus. The plant was found to be equally effective against gram-positive and negative bacteria. Studies are well underway to isolate and identify active compounds from chloroform fraction and ethyl acetate:methanol (1:1 sub-fraction, which can be used as

  1. Evaluation of antioxidant potential of leaves of Leonotis nepetifolia and its inhibitory effect on MCF7 and Hep2 cancer cell lines

    Science.gov (United States)

    Veerabadran, Usharani; Venkatraman, Anuradha; Souprayane, Aroumougame; Narayanasamy, Mathivanan; Perumal, Dhanalakshmi; Elumalai, Sagadevan; Sivalingam, Sindhu; Devaraj, Vadivelu; Perumal, Arumugam

    2013-01-01

    Objective To investigate the antioxidant and antiproliferative potential of Leonotis nepetifolia (L. nepetifolia) leaves. Methods The leaves of L. nepetifolia were subjected to extraction using three different solvents and the antioxidant potential of those extracts were tested by using various in vitro assays. Further, the best screened extract was analyzed for its phytochemical profile by both qualitative and quantitative assays. In order to determine its anti-proliferative activity, the best screened extract was treated with breast and laryngeal cancer cell lines such as MCF-7 cells and Hep2 cells, respectively. The cytotoxicity of the extract was also studied using MTT assay. The inhibitory effect of the extract of leaves of L. nepetifolia on the selected cell-line DNA was determined by DNA fragmentation assay. Also, the extract was subjected to TLC and bioautography analysis. Results The DPPH assay showed methanol extract of L. nepetifolia leaves to be more significant in scavenging free radicals with inhibition percentage of 60.57%. From the data obtained, the methanol extract proved to be significant in all anti-oxidant assays and this effect was well comparable with the standard used in the study. The predominant phytochemicals such as phenols and flavonoids were further quantified as 0.107% and 0.089%. The cytotoxicity assay showed that the cell viability increased with increasing concentration of methanol extract. In addition, the extract caused dose dependent damage to the cancer cell lines MCF-7 and Hep2. Conclusions Our study suggests that the leaves of L. nepetifolia were significant in scavenging free radicals and causing damage to proliferative cells. Further mechanistic studies would help in proving the efficiency of the selected plant under in vivo conditions.

  2. Phytochemical and antiproliferative activity of proso millet.

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    Lizhen Zhang

    Full Text Available The phytochemical content, antioxidant activity and antiproliferative properties of three diverse varieties of proso millet are reported. The free phenolic content ranged from 27.48 (Gumi 20 to 151.14 (Mi2504-6 mg gallic acid equiv/100 g DW. The bound phenolic content ranged from 55.95 (Gumi20 to 305.81 (Mi2504-6 mg gallic acid equiv/100 g DW. The percentage contribution of bound phenolic to the total phenolic content of genotype samples analyzed ranged between 62.08% and 67.05%. Ferulic acid and chlorogenic acid are the predominant phenolic acid found in bound fraction. Caffeic acid and p-coumaric acid were also detected. Syringic acid was detected only in the free fraction. The antioxidant activity was assessed using the hydrophilic peroxyl radical scavenging capacity (PSC assay. The PSC antioxidant activity of the free fraction ranged from 57.68 (Mi2504-6 to 147.32 (Gumi20 µmol of vitamin C equiv/100 g DW. The PSC antioxidant activity of the bound fraction ranged from 95.38 (Mizao 52 to 136.48 (Gumi 20 µmol of vitamin C equiv/100 g DW. The cellular antioxidant activity (CAA of the extract was assessed using the HepG2 model. CAA value ranged from 2.51 to 6.10 µmol equiv quercetin/100 g DW. Antiproliferative activities were also studied in vitro against MDA human breast cancer and HepG2 human liver cancer cells. Results exhibited a differential and possible selective antiproliferative property of the proso millet. These results may be used to direct the consumption of proso millet with improved health properties.

  3. Antiproliferative and apoptotic effects of spanish honeys

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    Paloma Morales

    2013-01-01

    Full Text Available Background: Current evidence supports that consumption of polyphenols has beneficial effects against numerous diseases mostly associated with their antioxidant activity. Honey is a good source of antioxidants since it contains a great variety of phenolic compounds. Objective: The main objective of this work was to investigate the antiproliferative and apoptotic effects of three crude commercial honeys of different floral origin (heather, rosemary and polyfloral honey from Madrid Autonomic Community (Spain as well as of an artificial honey in human peripheral blood promyelocytic leukemia cells (HL-60. Material and Methods: HL-60 cells were cultured in the presence of honeys at various concentrations for up to 72 hours and the percentage of cell viability was evaluated by MTT assay. Apoptotic cells were identified by chromatin condensation and flow cytometry analysis. ROS production was determined using 2΄,7΄-dichlorodihydrofluorescein diacetate (H 2 DCFDA. Results: The three types of crude commercial honey induced apoptosis in a concentration and time dependent-manner. In addition, honeys with the higher phenolic content, heather and polyfloral, were the most effective to induce apoptosis in HL-60 cells. However, honeys did not generate reactive oxygen species (ROS and N-acetyl-L-cysteine (NAC could not block honeys-induced apoptosis in HL-60 cells. Conclusion: These data support that honeys induced apoptosis in HL-60 cells through a ROS-independent cell death pathway.Moreover, our findings indicate that the antiproliferative and apoptotic effects of honey varied according to the floral origin and the phenolic content.

  4. Cellular radiosensitivity of small-cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Krarup, M; Poulsen, H S; Spang-Thomsen, M

    1997-01-01

    . The multitarget single hit model was applied to calculate the cellular radiosensitivity (D0), the capacity for sublethal damage repair (Dq), and the extrapolation number (n). Values for alpha and beta were determined from best-fit curves according to the linear-quadratic model and these values were applied...... to calculate the surviving fraction after 2-Gy irradiation (SF2). RESULTS: In our investigation, the extrapolation method proved to be inappropriate for the study of in vitro cellular radiosensitivity due to lack of reproducibility. The results obtained by the clonogenic assay showed that the cell lines...

  5. Aplysinopsin Analogs: Synthesis and Anti-proliferative Activity of Substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones

    OpenAIRE

    Reddy, Y. Thirupathi; Reddy, P. Narsimha; Koduru, Srinivas; Damodaran, Chendil; Crooks, Peter A.

    2010-01-01

    A series of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione (3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC50 ...

  6. DNA content analysis of insect cell lines by flow cytometry

    OpenAIRE

    Léry, Xavier; Charpentier, Guy; Belloncik, Serge

    1999-01-01

    The DNA content of insect cell lines (6 lepidoptera, 1 coleoptera and 1 diptera) was determined by flow cytometry. The DNA profiles of the 8 cell lines tested were different. They were characterized by the presence of several peaks (2 to 7) corresponding to different ploidy levels, by differences in the fluorescence intensity of each peak and by the proportion of cells in each peak. Two cell lines (Cf124 and BmN) were constituted of 2 distinct populations of cells. The DNA profiles of the cel...

  7. Ctotoxic and apoptogenic effects of Perovskia abrotanoides flower extract on MCF-7 and HeLa cell lines

    Science.gov (United States)

    Geryani, Mohamad Ali; Mahdian, Davood; Mousavi, Seyed Hadi; Hosseini, Azar

    2016-01-01

    Objective: Perovskia abrotanoides Karel, belongs to the family Lamiaceae and grows wild alongside the mountainous roads inarid and cold climate of Northern Iran. The anti-tumor activity of P. abrotanoides root extract has been shown previously. This study was designed to examine in vitro anti-proliferative and pro-apoptotic effects of flower extract of P. abrotanoides on MCF-7 and Hela cell lines. Materials and Methods: Cells were cultured in DMEM medium with 10% fetal bovine serum, 100 units/ml penicillin and 100 µg/ml streptomycin and incubated with different concentrations of plant extracts. Cell viability was quantified by MTT assay. Apoptotic cells were determined using propidium iodide (PI) staining of DNA fragmentation by flow cytometry (sub-G1 peak). Results: P. abrotanoides extract inhibited the growth of malignant cells in a time and dose-dependent manner and 1000 µg/ml of extract following 48h of incubation was the most cytotoxic dose against Hela cell in comparison with other doses; however, in MCF-7 cells,1000 and 500 µg/ml PA induced toxicity at all time points but with different features.. Analysis of flowcytometry histogram of treated cells compared with control cells indicated that the cytotoxic effect is partly due toapoptosis induction. Conclusion: Hydro-alcoholic extract of P. abrotanoides flowers inhibits the growth of MCF-7 and HeLa cell lines, partly via inducing apoptosis. Their inhibitory effect was increased in a time and dose-dependent manner, especially in MCF7 cells. However, further studies are needed to reveal the mechanisms of P. abrotanoides extract-induced cell death.

  8. Ctotoxic and apoptogenic effects of Perovskia abrotanoides flower extract on MCF-7 and HeLa cell lines

    Directory of Open Access Journals (Sweden)

    Mohamad Ali Geryani

    2016-06-01

    Full Text Available Objective: Perovskia abrotanoides Karel, belongs to the family Lamiaceae and grows wild alongside the mountainous roads inarid and cold climate of Northern Iran. The anti-tumor activity of P. abrotanoides root extract has been shown previously. This study was designed to examine in vitro anti-proliferative and pro-apoptotic effects of flower extract of P. abrotanoides on MCF-7 and Hela cell lines. Materials and Methods: Cells were cultured in DMEM medium with 10% fetal bovine serum, 100 units/ml penicillin and 100 µg/ml streptomycin and incubated with different concentrations of plant extracts. Cell viability was quantified by MTT assay. Apoptotic cells were determined using propidium iodide (PI staining of DNA fragmentation by flow cytometry (sub-G1 peak. Results: P. abrotanoides extract inhibited the growth of malignant cells in a time and dose-dependent manner and 1000 µg/ml of extract following 48h of incubation was the most cytotoxic dose against Hela cell in comparison with other doses; however, in MCF-7 cells,1000 and 500 µg/ml PA induced toxicity at all time points but with different features.. Analysis of flowcytometry histogram of treated cells compared with control cells indicated that the cytotoxic effect is partly due toapoptosis induction. Conclusion: Hydro-alcoholic extract of P. abrotanoides flowers inhibits the growth of MCF-7 and HeLa cell lines, partly via inducing apoptosis. Their inhibitory effect was increased in a time and dose-dependent manner, especially in MCF7 cells. However, further studies are needed to reveal the mechanisms of P. abrotanoides extract-induced cell death.

  9. The Inhibitory Effect of Somatostatin Analogue RC-160 on the Growth of Endometrial Carcinoma Cell Line HEC-1A

    Institute of Scientific and Technical Information of China (English)

    Liang Rui; Tang Xiaohui; Zhu Gaixia; Gao Yane; Guo Yin

    2004-01-01

    Objective:To evaluate the inhibitory effect of somatostatin analogue RC-160 on the growth of human endometrial cancer cells (HEC-1A) in vitro. Method: RT-PCR was used to examine the existence of somatostatin receptors on the HEC-1A cells. The anti-proliferative effect of RC-160 on the growth of HEC-1A cells was detected by using BrdU incorporation test. TUNEL staining was used to find out whether apoptosis was involved in the inhibitory process. Result: All the five somatostatin receptor subtypes were demonstrated in HEC-1A cells. RC-160 reduced the HEC-1A cell growth stimulated by serum in a dose-dependent manner. The effect was maximal at the concentration of 10-5M after 48 hours' treatment. No apoptosis was detected. Conclusion:Somatostatin analogue RC-160 can inhibit the proliferation of endometrial carcinoma cell line HEC-1A through binding to the somatostatin receptors on the cells. It seems that apoptosis is not mainly responsible for the inhibition.

  10. Carbon source and myc expression influence the antiproliferative actions of metformin.

    Science.gov (United States)

    Javeshghani, Shiva; Zakikhani, Mahvash; Austin, Shane; Bazile, Miguel; Blouin, Marie-José; Topisirovic, Ivan; St-Pierre, Julie; Pollak, Michael N

    2012-12-01

    Epidemiologic and experimental data have led to increased interest in possible roles of biguanides in cancer prevention and/or treatment. Prior studies suggest that the primary action of metformin is inhibition of oxidative phosphorylation, resulting in reduced mitochondrial ATP production and activation of AMPK. In vitro, this may lead to AMPK-dependent growth inhibition if AMPK and its effector pathways are intact or to an energetic crisis if these are defective. We now show that the effect of exposure of several transformed cell lines to metformin varies with carbon source: in the presence of glutamine and absence of glucose, a 75% decrease in cellular ATP and an 80% decrease in cell number is typical; in contrast, when glucose is present, metformin exposure leads to increased glycolysis, with only a modest reduction in ATP level and cell number. Overexpression of myc was associated with sensitization to the antiproliferative effects of metformin, consistent with myc involvement in "glutamine addiction". Our results reveal previously unrecognized factors that influence metformin sensitivity and suggest that metformin-induced increase in glycolysis attenuates the antiproliferative effects of the compound. PMID:23041548

  11. Efficiently prepared ephedrine alkaloids-free Ephedra Herb extract: a putative marker and antiproliferative effects.

    Science.gov (United States)

    Oshima, Naohiro; Yamashita, Tadatoshi; Hyuga, Sumiko; Hyuga, Masashi; Kamakura, Hiroyuki; Yoshimura, Morio; Maruyama, Takuro; Hakamatsuka, Takashi; Amakura, Yoshiaki; Hanawa, Toshihiko; Goda, Yukihiro

    2016-07-01

    Ephedrine alkaloids (EAs) have been considered the main pharmacologically active substances in Ephedra Herb (, Mao; EH) since they were first identified by Prof. N. Nagai, and are known to induce palpitation, hypertension, insomnia, and dysuria as side effects. Therefore, the administration of drugs containing EH to patients with cardiovascular-related diseases is severely contraindicated. While our previous studies suggest that some of the effects of EH may not be due to EAs, considering their side effects would be expedient to develop a new EAs-free EH extract (EFE). Here, we established a preparation method for EFE and revealed its chemical composition, including the content of herbacetin, a flavonoid aglycon present in EH and a potential putative marker for EFE quality control. In addition, we showed the antiproliferative effects of EFE against the H1975 non-small cell lung cancer (NSCLC) cell line. EFE was prepared from EH extract using the ion exchange resin SK-1B. LC/Orbitrap MS analysis revealed the removal of EAs, 6-methoxykynurenic acid, and 6-hydroxykynurenic acid from the original extract. Quantitative analysis of herbacetin using LC/MS in acid-hydrolyzed EFE showed that its content was 0.104 %. Although several alkaloidal constituents were removed from EH extract, the antiproliferative effect of EFE against H1975 cells was comparable to that of EH extract. These results indicate that EFE retained the anticancer effect of EH and demonstrated its potential for future development as a new herbal medicine with reduced side effects. PMID:26976141

  12. Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress

    Directory of Open Access Journals (Sweden)

    Yeh Chi-Chen

    2012-08-01

    Full Text Available Abstract Background Methanolic extracts of Gracilaria tenuistipitata (MEGT were obtained from the edible red algae. Previously, we found that water extract of G. tenuistipitata was able to modulate oxidative stress-induced DNA damage and its related cellular responses. Methods In this study, the methanol extraction product MEGT was used to evaluate the cell growth inhibition in oral cancer cells and its possible mechanism was investigated. Results The cell viability of MEGT treated Ca9-22 oral cancer cell line was significantly decreased in a dose–response manner (p p p p p 2(3 intensity for mitochondrial membrane potential (MMP of MEGT-treated Ca9-22 cancer cells was significantly decreased in a dose–response manner (p  Conclusions These results indicated that MEGT had apoptosis-based cytotoxicity against oral cancer cells through the DNA damage, ROS induction, and mitochondrial depolarization. Therefore, MEGT derived from the edible algae may have potential therapeutic effects against oral squamous cell carcinoma (OSCC.

  13. Influence of vitamin D on cisplatin sensitivity in testicular germ cell cancer-derived cell lines and in a NTera2 xenograft model

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Blomberg Jensen, Martin; Nielsen, John Erik;

    2013-01-01

    The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has anti-proliferative, pro-apoptotic, and pro-differentiating effects in somatic cancer cells in vitro and in vivo. 1,25(OH)(2)D(3) also augments the anti-tumor effects of several chemotherapeutic agents, including...... cisplatin, which may have clinical relevance. Given the pro-differentiation effect of vitamin D recently demonstrated in testicular germ cell tumors (TGCTs), we hypothesized that 1,25(OH)(2)D(3) could be a beneficial adjunctive to existing chemotherapy regime used to treat these tumors. In this study, cell...... survival effects of 1,25(OH)(2)D(3), another pro-differentiation compound, retinoic acid and cisplatin were investigated in TGCT-derived cell lines in vitro. 1,25(OH)(2)D(3) augmented the effect of cisplatin in an embryonal carcinoma-derived cell line (NTera2), possibly through downregulation...

  14. Evaluation of anticancer potential of Bacopa monnieri L. against MCF-7 and MDA-MB 231 cell line

    Directory of Open Access Journals (Sweden)

    Md. Nasar Mallick

    2015-01-01

    Full Text Available Background: The ethanolic extract of Bacopa monnieri contains bacoside A and B, brahmin, cucurbitacins, and betulinic acid. Currently, cucurbitacins have also been reported for their strong anti-tumorigenic and anti-proliferative activity by inducing cell cycle arrest at the G2/M phase and formation of multiplied cells. The present study was carried out to evaluate the in vitro cytotoxic activity of ethanolic extract of dichloromethane (DCM fraction of B. monnieri on two different cell lines. Materials and Methods: The ethanolic extract of B. monnieri was prepared using soxhlet extraction method and different fractions (hexane, DCM, methanol, acetone, and water of ethanolic extracts were prepared. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay of ethanolic extract and of all fractions was carried out on MCF-7 and MDA-MB 231 cell lines. The presence of cucurbitacins and betulinic acid in these fractions was confirmed by high-performance thin layer chromatography. Results: The IC50 values of ethanolic extract of B. monnieri in MCF-7 and MDA-MB 231 cell lines were 72.0 μg/mL and 75.0 μg/mL, respectively. The DCM fraction of B. monnieri showed maximum cytotoxic activity among all fraction upto 72 h and was found to be 57.0 μg/mL and 42.0 μg/mL, respectively. Conclusion: The results showed good cytotoxic activity in DCM fraction in both the cell lines may be due to the presence of cucurbitacins and betulinic acid in DCM fraction.

  15. Trichloroethylene toxicity in a human hepatoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Thevenin, E.; McMillian, J. [Medical Univ. of Charleston South Carolina, SC (United States)

    1994-12-31

    The experiments conducted in this study were designed to determine the usefullness of hepatocyte cultures and a human hepatoma cell line as model systems for assessing human susceptibility to hepatocellular carcinoma due to exposure to trichloroethylene. The results from these studies will then be analyzed to determine if human cell lines can be used to conduct future experiments of this nature.

  16. Derivation of the human embryonic stem cell line RCM1

    Directory of Open Access Journals (Sweden)

    P.A. De Sousa

    2016-03-01

    Full Text Available The human embryonic stem cell line RCM-1 was derived from a failed to fertilise egg undergoing parthenogenetic stimulation. The cell line shows normal pluripotency marker expression and differentiation to three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data is available.

  17. Derivation of the human embryonic stem cell line RCM1.

    Science.gov (United States)

    De Sousa, P A; Tye, B J; Sneddon, S; Bruce, K; Dand, P; Russell, G; Collins, D M; Greenshields, A; McDonald, K; Bradburn, H; Gardner, J; Downie, J M; Courtney, A; Brison, D R

    2016-03-01

    The human embryonic stem cell line RCM-1 was derived from a failed to fertilise egg undergoing parthenogenetic stimulation. The cell line shows normal pluripotency marker expression and differentiation to three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data is available. PMID:27346018

  18. Cancer and inflammation studies using zebrafish cell lines

    NARCIS (Netherlands)

    He, Shuning

    2010-01-01

    As the zebrafish, Danio rerio, has been increasingly used as an animal model for biomedical research, we aimed to establish zebrafish cell line models for inflammation and cancer studies in this thesis. Several zebrafish cell lines were characterized and their genetic and physiological properties we

  19. Characterization of xenoantiserum produced against B cell acute lymphoblastic leukemia cell line

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    Akagi,Tadaatsu

    1982-10-01

    Full Text Available Antiserum was produced in white rabbit by intravenously injecting living cells of a B cell acute lymphoblastic leukemia (ALL line (BALL-1. The reactivity of the antiserum against various lymphoid cell lines was examined by membrane immunofluorescence after appropriate absorption. Serum absorbed with non-T, non-B (NALL-1 and T-ALL (TALL-1 cells recognized B cell antigens distinct from Ia-like antigens on both normal and neoplastic B cells. After further absorption with tonsillar cells or normal B cell line (KO-HL-3, it reacted only with BALL-1 cells and did not react with other leukemia/lymphoma and normal B cell lines. The serum absorbed with tonsillar cells reacted only with BALL-1 and some B cell lines. Thus we were able to obtain antisera with specificity to B cell antigen, B-ALL antigen, and B cell line antigen.

  20. Regulated expression of erythropoietin by two human hepatoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, M.A.; Glass, G.A.; Cunningham, J.M.; Bunn, H.F.

    1987-11-01

    The development of a cell culture system that produces erythropoietin (Epo) in a regulated manner has been the focus of much effort. The authors have screened multiple renal and hepatic cell lines for either constitutive or regulated expression of Epo. Only the human hepatoma cell lines, Hep3B and HepG2, made significant amounts of Epo as measured both by radioimmunoassay and in vitro bioassay (as much as 330 milliunits per 10/sup 6/ cells in 24 hr). The constitutive production of Epo increased dramatically as a function of cell density in both cell lines. At cell densities < 3.3 x 10/sup 5/ cells per cm/sup 2/, there was little constitutive release of Epo in the medium. With Hep3B cells grown at low cell densities, a mean 18-fold increase in Epo expression was seen in response to hypoxia and a 6-fold increase was observed in response to incubation in medium containing 50 ..mu..M cobalt(II) chloride. At similar low cell densities, Epo production in HepG2 cells could be enhanced an average of about 3-fold by stimulation with either hypoxia or cobalt(II) chloride. Upon such stimulation, both cell lines demonstrated markedly elevated levels of Epo mRNA. Hence, both Hep3B and HepG2 cell lines provide an excellent in vitro system in which to study the physiological regulation of Epo expression.

  1. siRNA-mediated silencing of Cockayne Cyndrome group B gene potentiates radiation-induced apoptosis and antiproliferative effect in HeLa cells

    Institute of Scientific and Technical Information of China (English)

    LIU Feng; YU Zi-jian; SUI Jian-li; BAI Bei; ZHOU Ping-kun

    2006-01-01

    Background Cockayne syndrome (CS) is a rare human genetic disorder characterized by increased UV sensitivity, developmental abnormalities and premature aging. Cells isolated from individuals with CS have a defect in transcription-coupled DNA repair. Despite the repair defect, there is no any increased risk of spontaneous or UV-induced cancer for CS individuals. The strategy of RNA interfering was used here to explore the potential radiosensitizing and anticancer activity of targeting CS group B (CSB) gene.Methods The vectors encoding CSB-specific siRNAs were constructed by inserting duplex siRNA encoding oligonucleotides into the plasmid psilencer TM 3.1. The cell lines expressing the CSB-siRNA were generated from HeLa cells transfected with the above vectors. Colony-forming ability was used to assay cell survival. Cell cycle was analyzed by FACScan flow cytometry. The apoptosis was measured by detecting the accumulation of sub-G1 population as well as by fluorescence staining assay. Reverse transcriptase polymerase chain reaction (RT-PCR)was used to semi-quantify mRNA expression. Protein level was detected by Western blotting analysis.Results Two constructs encoding CSB-specific siRNA were generated, both of them resulted in remarkable suppression on CSB expression in HeLa cells, and led to an increased sensitivity to γ-ray and UV light.siRNA-mediated silencing of CSB decreased cell proliferation rate, increased spontaneous apoptosis as well as the occurrence of UV- or cisplatin-induced apoptosis by 2 to 3.5 fold. A significant S phase blockage and a remarkable reduction of G1 population were induced in control HeLa cells at 18 hours after being exposed to 10J/m2 of UV light. The S phase blockage was also observed in UV-irradiated CSB-siRNA transfected HeLa cells,but the extent of increased S phase population was lower than that in the UV-irradiated control cells. No or a relative weak reduction on G1 phase population was observed in UV-irradiated CSB

  2. Human embryonic stem cell lines derived from the Chinese population

    Institute of Scientific and Technical Information of China (English)

    Zhen Fu FANG; Fan JIN; Hui GAI; Ying CHEN; Li WU; Ai Lian LIU; Bin CHEN; Hui Zhen SHENG

    2005-01-01

    Six human embryonic stem cell lines were established from surplus blastocysts. The cell lines expressed alkaline phosphatase and molecules typical of primate embryonic stem cells, including Oct-4, Nanog, TDGF1, Sox2, EBAF,Thy-1, FGF4, Rex-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. Five of the six lines formed embryoid bodies that expressed markers of a variety of cell types; four of them formed teratomas with tissue types representative of all three embryonic germ layers. These human embryonic stem cells are capable of producing clones of undifferentiated morphology, and one of them was propagated to become a subline. Human embryonic stem cell lines from the Chinese population should facilitate stem cell research and may be valuable in studies of population genetics and ecology.

  3. The transcriptional diversity of 25 Drosophila cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Cherbas, L.; Willingham, A.; Zhang, D.; Yang, L.; Zou, Y.; Eads, B. D.; Carlson, J. W.; Landolin, J. M.; Kapranov, P.; Dumais, J.; Samsonova, A.; Choi, J. -H.; Roberts, J.; Davis, C. A.; Tang, H.; van Baren, M. J.; Ghosh, S.; Dobin, A.; Bell, K.; Lin, W.; Langton, L.; Duff, M. O.; Tenney, A. E.; Zaleski, C.; Brent, M. R.; Hoskins, R. A.; Kaufman, T. C.; Andrews, J.; Graveley, B. R.; Perrimon, N.; Celniker, S. E.; Gingeras, T. R.; Cherbas, P.

    2010-12-22

    Drosophila melanogaster cell lines are important resources for cell biologists. Here, we catalog the expression of exons, genes, and unannotated transcriptional signals for 25 lines. Unannotated transcription is substantial (typically 19% of euchromatic signal). Conservatively, we identify 1405 novel transcribed regions; 684 of these appear to be new exons of neighboring, often distant, genes. Sixty-four percent of genes are expressed detectably in at least one line, but only 21% are detected in all lines. Each cell line expresses, on average, 5885 genes, including a common set of 3109. Expression levels vary over several orders of magnitude. Major signaling pathways are well represented: most differentiation pathways are ‘‘off’’ and survival/growth pathways ‘‘on.’’ Roughly 50% of the genes expressed by each line are not part of the common set, and these show considerable individuality. Thirty-one percent are expressed at a higher level in at least one cell line than in any single developmental stage, suggesting that each line is enriched for genes characteristic of small sets of cells. Most remarkable is that imaginal discderived lines can generally be assigned, on the basis of expression, to small territories within developing discs. These mappings reveal unexpected stability of even fine-grained spatial determination. No two cell lines show identical transcription factor expression. We conclude that each line has retained features of an individual founder cell superimposed on a common ‘‘cell line‘‘ gene expression pattern. Wereport the transcriptional profiles of 25 Drosophila melanogaster cell lines, principally by whole-genome tiling microarray analysis of total RNA, carried out as part of the modENCODE project. The data produced in this study add to our knowledge of the cell lines and of the Drosophila transcriptome in several ways. We summarize the expression of previously annotated genes in each of the 25 lines with emphasis on what

  4. Organotin Compound Derived from 3-Hydroxy-2-formylpyridine Semicarbazone: Synthesis, Crystal Structure, and Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Joanna Wiecek

    2010-01-01

    Full Text Available The novel diphenyltin(IV compound [Ph2(HyFoScSn] (2, where H2HyFoSc (1 is 3-hydroxy-2-formylpyridine semicarbazone, was prepared and characterized by vibrational and NMR (1H, 13C spectroscopy. The structure of [Ph2(HyFoScSn] was confirmed by single-crystal X-ray crystallography. The doubly deprotonated ligand is coordinated to the tin atom through the enolic-oxygen, the azomethine-nitrogen, and phenolic-oxygen, and so acts as an anionic tridentate ligand with the ONO donors. Two carbon atoms complete the fivefold coordination at the tin(IV center. Intermolecular hydrogen bonding, C-H→, and → interactions combine to stabilize the crystal structure. Compounds 1 and 2 have been evaluated for antiproliferative activity in vitro against the cells of three human tumor cell lines: MCF-7 (human breast cancer cell line, T24 (bladder cancer cell line, A549 (nonsmall cell lung carcinoma, and a mouse fibroblast L-929 cancer cell line.

  5. Anti-proliferative effects of polyphenols from pomegranate rind (Punica granatum L.) on EJ bladder cancer cells via regulation of p53/miR-34a axis.

    Science.gov (United States)

    Zhou, Benhong; Yi, Huilan; Tan, Jun; Wu, Yue; Liu, Gang; Qiu, Zhenpeng

    2015-03-01

    miRNAs and their validated miRNA targets appear as novel effectors in biological activities of plant polyphenols; however, limited information is available on miR-34a mediated cytotoxicity of pomegranate rind polyphenols in cancer cell lines. For this purpose, cell viability assay, Realtime quantitative PCR for mRNA quantification, western blot for essential protein expression, p53 silencing by shRNA and miR-34a knockdown were performed in the present study. EJ cell treatment with 100 µg (GAE)/mL PRE for 48 h evoked poor cell viability and caspase-dependent pro-apoptosis appearance. PRE also elevated p53 protein and triggered miR-34a expression. The c-Myc and CD44 were confirmed as direct targets of miR-34a in EJ cell apoptosis induced by PRE. Our results provide sufficient evidence that polyphenols in PRE can be potential molecular clusters to suppress bladder cancer cell EJ proliferation via p53/miR-34a axis. PMID:25572695

  6. β-Caryophyllene, a Compound Isolated from the Biblical Balm of Gilead (Commiphora gileadensis, Is a Selective Apoptosis Inducer for Tumor Cell Lines

    Directory of Open Access Journals (Sweden)

    Eitan Amiel

    2012-01-01

    Full Text Available The biblical balm of Gilead (Commiphora gileadensis was investigated in this study for anticancerous activity against tumor cell lines. The results obtained from ethanol-based extracts and from essential oils indicated that β-caryophyllene (trans-(1R,9S-8-methylene-4,11,11-trimethylbicyclo[7.2.0]undec-4-ene is a key component in essential oils extracted from the balm of Gilead. β-Caryophyllene can be found in spice blends, citrus flavors, soaps, detergents, creams, and lotions, as well as in a variety of food and beverage products, and it is known for its anti-inflammatory, local anaesthetic, and antifungal properties. It is also a potent cytotoxic compound over a wide range of cell lines. In the current paper, we found that Commiphora gileadensis stem extracts and essential oil have an antiproliferative proapoptotic effect against tumor cells and not against normal cells. β-caryophyllene caused a potent induction of apoptosis accompanied by DNA ladder and caspase-3 catalytic activity in tumor cell lines. In summary, we showed that C. gileadensis stems contain an apoptosis inducer that acts, in a selective manner, against tumor cell lines and not against normal cells.

  7. Derivation of human embryonic stem cell line Genea022

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea022 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype and male allele pattern through CGH and STR analysis. Pluripotency of Genea022 was demonstrated with 84% of cells expressed Nanog, 98% Oct4, 55% Tra1–60 and 97% SSEA4, gave a Pluritest Pluripotency score of 42.95, Novelty of 1.23, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.

  8. Derivation of Genea052 human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea052 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype and male allele pattern through CGH and STR analysis. Pluripotency of Genea052 was demonstrated with 85% of cells expressing Nanog, 87% Oct4, 60% Tra1-60 and 97% SSEA4, a PluriTest Pluripotency score of 27.21, Novelty score of 1.2 and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and any visible contamination.

  9. Derivation of Genea047 human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea047 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype and female allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea047 was demonstrated with 88% of cells expressing Nanog, 95% Oct4, 59% Tra1-60 and 99% SSEA4, a PluriTest Pluripotency score of 30.86, Novelty score of 1.23 and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and any visible contamination.

  10. Derivation of Genea015 human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea015 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype and male Allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea015 was demonstrated with 80% of cells expressing Nanog, 97% Oct4, 75% Tra1-60 and 98% SSEA4, a PluriTest Pluripotency score of 29.52, Novelty score of 1.3 and Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and any visible contamination.

  11. Derivation of human embryonic stem cell line Genea023

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea023 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XY karyotype and male allele pattern through CGH and STR analysis. Pluripotency of Genea023 was demonstrated with 85% of cells expressed Nanog, 98% Oct4, 55% Tra1-60 and 98% SSEA4, gave a Pluritest Pluripotency score of 42.76, Novelty of 1.23, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.

  12. Derivation of Genea042 human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea042 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated human feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype and female allele pattern through traditional karyotyping, CGH and STR analysis. Pluripotency of Genea042 was demonstrated with 81% of cells expressing Nanog, 95% Oct4, 53% Tra1-60 and 97% SSEA4, a PluriTest Pluripotency score of 30.06, Novelty score of 1.24 and Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and any visible contamination.

  13. Cytotoxinic Mechanism of Hydroxyapatite Nanoparticles on Human Hepatoma Cell Lines

    Institute of Scientific and Technical Information of China (English)

    CAO Xian-ying; QI Zhi-tao; DAI Hong-lian; YAN Yu-hua; LI Shi-pu

    2003-01-01

    Stable and single-dispersed HAP nanoparticles were synthesized with chemical method assisted by ultrasonic treatment.HAP nanoparticles were surveyed by AFM and Zataplus.The effect on the Bel-7402 human hepatoma cell lines treated with HAP nanoparticles was investigated by the MTT methods and observation of morphology,and the mechanism was studied in changes of cell cycle and ultrastructure.The result shows that inhibition of HAP nanoparticles on the Bel-7402 human hepatoma cell lines is obviously in vitro.HAP nanoparticles the entered cancer cytoplasm,and cell proliferation is stopped at G1 phase of cell cycle,thus,cancer cells die directly.

  14. Recombinant protein production from stable mammalian cell lines and pools.

    Science.gov (United States)

    Hacker, David L; Balasubramanian, Sowmya

    2016-06-01

    We highlight recent developments for the production of recombinant proteins from suspension-adapted mammalian cell lines. We discuss the generation of stable cell lines using transposons and lentivirus vectors (non-targeted transgene integration) and site-specific recombinases (targeted transgene integration). Each of these methods results in the generation of cell lines with protein yields that are generally superior to those achievable through classical plasmid transfection that depends on the integration of the transfected DNA by non-homologous DNA end-joining. This is the main reason why these techniques can also be used for the generation of stable cell pools, heterogenous populations of recombinant cells generated by gene delivery and genetic selection without resorting to single cell cloning. This allows the time line from gene transfer to protein production to be reduced.

  15. Establishment of human embryonic stem cell line from gamete donors

    Institute of Scientific and Technical Information of China (English)

    LI Tao; ZHOU Can-quan; MAI Qing-yun; ZHUANG Guang-lun

    2005-01-01

    Background Human embryonic stem (HES) cell derived from human blastocyst can be propagated indefinitely in the primitive undifferentiated state while remaining pluripotent. It has exciting potential in human developmental biology, drug discovery, and transplantation medicine. But there are insufficient HES cell lines for further study. Methods Three oocyte donors were studied, and 3 in vitro fertilization (IVF) cycles were carried out to get blastocysts for the establishment of HES cell line. Isolated from blastocysts immunosurgically, inner cell mass (ICM) was cultured and propagated on mouse embryonic fibroblasts (MEFs). Once established, morphology, cell surface markers, karyotype and differentiating ability of the cell line were thoroughly analyzed.Results Four ICMs from 7 blastocysts were cultured on MEFs. After culture, one cell line (cHES-1) was established and met the criteria for defining human pluripotent stem cells including a series of markers used to identify pluripotent stem cells, morphological similarity to primate embryonic stem cells and HES reported else where. Normal and stable karyotype maintained over 60 passages, and demonstrated ability to differentiate into a wide variety of cell types.Conclusions HES cell lines can be established from gamete donors at a relatively highly efficient rate. The establishment will exert a widespread impact on biomedical research.

  16. Susceptibility of various cell lines to Neospora caninum tachyzoites cultivation

    Directory of Open Access Journals (Sweden)

    Khordadmehr, M.,

    2014-05-01

    Full Text Available Neospora caninum is a coccidian protozoan parasite which is a major cause of bovine abortions and neonatal mortality in cattle, sheep, goat and horse. Occasionally, cultured cells are used for isolation and multiplication of the agent in vitro with several purposes. In this study the tachyzoite yields of N. caninum were compared in various cell cultures as the host cell lines. Among the cell cultures tested, two presented good susceptibility to the agent: cell lines Vero and MA-104. SW742 and TLI (in vitro suspension culture of lymphoid cells infected with Theileria lestoquardi showed moderate sensitivity. No viable tachyzoite were detected in the culture of MDCK and McCoy cell lines. These results demonstrate that MA-104 and SW742 cells present adequate susceptibility to N. caninum compared to Vero cells, which have been largely used to multiply the parasite in vitro. Moreover, these have easy manipulation, fast multiplication and relatively low nutritional requirements. In addition, the result of this study showed that TLI cell line as a suspension cell culture is susceptible to Nc-1 tachyzoites infection and could be used as an alternative host cell line for tachyzoites culture in vitro studies.

  17. Establishment of Germ-line Competent C57BL/6J Embryonic Stem Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Gui-jun YAN; Zheng GU; Jian WANG; Jia-ke TSO

    2004-01-01

    Objective To establish C57BL/6J embryonic stem (ES) cell lines with potential germline contribution Methods ES cells were isolated from blastocyst inner cell mass of C57BL/6J mice, and cultured for 15 passages, and then injected into blastococels of lCR mice blastocysts to establish chimeric mice.Results Three ES cell lines (mC57ESl,mC57ES3, mC57ES7) derived from the inner cell mass of C57BL/6J mice blastocysts were established. They were characteristic of undifferentiated state, including normal XY karyotype, expression of a specific cell surface marker "stage-specific embryonic antigen-1" and alkaline phosphatase in continuous passage. When injected into immunodeficient mice, mC5 7ES1 cells consis tently differentiated into derivatives of all three embryonic germ layers. When mC57ES1cells were transferred into ICR mice blastocysts, 4 chimeric mice have been obtained.One male of them revealed successful germ-line transmission. Conclussion We have obtained C57BL/6J ES cell lines with a potential germ-line contribution, which can be used to generate transgenic and gene knock-out mice.

  18. Chmp 1A is a mediator of the anti-proliferative effects of All-trans Retinoic Acid in human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Nguyen Hanh

    2009-02-01

    Full Text Available Abstract Background We recently have shown that Charged multivesicular protein/Chromatin modifying protein1A (Chmp1A functions as a tumor suppressor in human pancreatic tumor cells. Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year survival rate. Preclinical studies using ATRA for treating human pancreatic cancer suggest this compound might be useful for treatment of pancreatic cancer patients. However, the molecular mechanism by which ATRA inhibits growth of pancreatic cancer cells is not clear. The objective of our study was to investigate whether Chmp1A is involved in ATRA-mediated growth inhibition of human pancreatic tumor cells. Results We performed microarray studies using HEK 293T cells and discovered that Chmp1A positively regulated Cellular retinol-binding protein 1 (CRBP-1. CRBP-1 is a key regulator of All-trans retinoic acid (ATRA through ATRA metabolism and nuclear localization. Since our microarray data indicates a potential involvement of Chmp1A in ATRA signaling, we tested this hypothesis by treating pancreatic tumor cells with ATRA in vitro. In the ATRA-responsive cell lines, ATRA significantly increased the protein expression of Chmp1A, CRBP-1, P53 and phospho-P53 at serine 15 and 37 position. We found that knockdown of Chmp1A via shRNA abolished the ATRA-mediated growth inhibition of PanC-1 cells. Also, Chmp1A silencing diminished the increase of Chmp1A, P53 and phospho-P53 protein expression induced by ATRA. In the ATRA non-responsive cells, ATRA did not have any effect on the protein level of Chmp1A and P53. Chmp1A over-expression, however, induced growth inhibition of ATRA non-responsive cells, which was accompanied by an increase of Chmp1A, P53 and phospho-P53. Interestingly, in ATRA responsive cells Chmp1A is localized to the nucleus, which became robust upon ATRA treatment. In the ATRA-non-responsive cells, Chmp1A was mainly translocated to the plasma membrane upon ATRA treatment. Conclusion

  19. Growth Inhibiton of H uman Breast Cancer Cell Line MDA-MB-231 by Rosiglitazone through Activation of PPARy

    Institute of Scientific and Technical Information of China (English)

    Tao Zhang; Qian Zhang; Daixiong Chen; Jianxin Jiang; Qixin zhou

    2008-01-01

    To investigate the anti-proliferative effect ofrosiglitazone and its relationship to peroxisome proliferator-activated receptor γ(PPARγ)in human breast cancer cell lineMDA-MB-231 and evaluate the potential application value ofrosiglitazone for breast cancer therapy.METHoDS The cytostatic effect of rosiglitazone on MDA-MB-231 cellS was measured by the MTT assay.Cell-cyclekinetics.was assessed by flow cytometry.Apoptotic cells weredetermined by the TUNEL assay.MDA.MB-231 cells weretreated with rosiglitazone or in combination with the PPARyantagonist GW9662 to investigate the effect of rosiglitazone on cellproliferation and its relationship to PPARγ.RESUITS The results showed that rosiglitazone could inhibitgrowth of MDA-MB-231 cells in a dose-and time-dependentmanner with an IC50 value of 5.2 pmol/L at 24 h after the drugwas added into the culture.Cell cycle analysis showed that thepercentage of G0/G1 phase cells increased,S phase cells decreased,and cells were arrested in G1 phase with increasing concentrationsof rosiglitazone.Detectable signs of apoptotic cell death caused byrosiglitazone occurred at a concentration of 100 pmol/L and theapoptotic rate was(18±3)%.PPARγ selective antagonist GW9662could partially reverse the inhibitory effect of rosiglitazone onproliferation of MDA.MB-231 cells.CoNCLUSION It was concluded that rosiglitazone Can inhibitgrowth of MDA-MB-231 cells via PPARγ activation and a highconcentration of rosiglitazone can also induce MDA-MB-231 cellapoptosis.These results suggest that PPARv represents a putativemolecular target for chemopreventive therapy and rosiglitazonemay be effective in the treatment of breast cancer.

  20. Generation and characterization of human insulin-releasing cell lines

    OpenAIRE

    Joffé Elisa; Machado Marcel CC; Buchanan Cecilia; Terra Letícia F; Stigliano Iván; Krogh Karin; Peters Maria G; Labriola Leticia; Puricelli Lydia; Sogayar Mari C

    2009-01-01

    Abstract Background The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. Results We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which w...

  1. A Rare Class of New Dimeric Naphtoquiones from Diospyros lotus have Multidrug Reversal and Antiproliferative Effects

    Directory of Open Access Journals (Sweden)

    Dr. Abdur eRauf

    2015-12-01

    Full Text Available Three new dimeric naphthoquinones, 5,4′-dihydroxy-1′-methoxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,5′,8′-tetraone (1, 5′,8′-dihydroxy-5-methoxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,1′,4′-tetraone (2 and 8,5′,8′-trihydroxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,1′,4′-tetraone (3, were isolated from the roots of Diospyros lotus. Their structures were elucidated by spectroscopic techniques, including 1D and 2D NMR, such as HSQC, HMBS, NOESY and J resolved. Compounds 1-3 were evaluated for their effects on the reversion of multidrug resistance (MDR mediated by P-glycoprotein through use of the rhodamine-123 exclusion screening test on human ABCB1 gene transfected L5178Y mouse T-cell lymphoma. Compounds 1-3 were also assessed for their antiproliferative and cytotoxic effects on L5178 and L5178Y mouse T-cell lymphoma lines. Both 1 and 2 exhibited promising antiproliferative and MDR-reversing effects in a dose dependent manner. The effects of the tested compounds on the activity of doxorubicin were observed to vary from slight antagonism to antagonism.

  2. Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins

    OpenAIRE

    Lockwood, William W; Zejnullahu, Kreshnik; James E Bradner; Varmus, Harold

    2012-01-01

    Bromodomain and extra terminal domain (BET) proteins function as epigenetic signaling factors that associate with acetylated histones and facilitate transcription of target genes. Inhibitors targeting the activity of BET proteins have shown potent antiproliferative effects in hematological cancers through the suppression of c-MYC and downstream target genes. However, as the epigenetic landscape of a cell varies drastically depending on lineage, transcriptional coactivators such as BETs would ...

  3. Generation and characterization of human insulin-releasing cell lines

    Directory of Open Access Journals (Sweden)

    Joffé Elisa

    2009-06-01

    Full Text Available Abstract Background The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. Results We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which were cultured up to passage number 20. All cell lines secreted human insulin and C-peptide. These cell lines expressed neuroendocrine and islets markers, confirming the expression profile found in the biopsies. Although all beta cell lineages survived an anchorage independent culture, none of them were able to invade an extracellular matrix substrate. Conclusion We have established three human insulin-releasing cell lines which maintain antigenic characteristics and insulin secretion profiles of the original tumors. These cell lines represent valuable tools for the study of molecular events underlying beta cell function and dysfunction.

  4. Generation and characterization of human insulin-releasing cell lines

    Science.gov (United States)

    Labriola, Leticia; Peters, Maria G; Krogh, Karin; Stigliano, Iván; Terra, Letícia F; Buchanan, Cecilia; Machado, Marcel CC; Joffé, Elisa Bal de Kier; Puricelli, Lydia; Sogayar, Mari C

    2009-01-01

    Background The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. Results We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which were cultured up to passage number 20. All cell lines secreted human insulin and C-peptide. These cell lines expressed neuroendocrine and islets markers, confirming the expression profile found in the biopsies. Although all beta cell lineages survived an anchorage independent culture, none of them were able to invade an extracellular matrix substrate. Conclusion We have established three human insulin-releasing cell lines which maintain antigenic characteristics and insulin secretion profiles of the original tumors. These cell lines represent valuable tools for the study of molecular events underlying beta cell function and dysfunction. PMID:19545371

  5. Investigation of radiosensitivity gene signatures in cancer cell lines.

    Directory of Open Access Journals (Sweden)

    John S Hall

    Full Text Available Intrinsic radiosensitivity is an important factor underlying radiotherapy response, but there is no method for its routine assessment in human tumours. Gene signatures are currently being derived and some were previously generated by expression profiling the NCI-60 cell line panel. It was hypothesised that focusing on more homogeneous tumour types would be a better approach. Two cell line cohorts were used derived from cervix [n = 16] and head and neck [n = 11] cancers. Radiosensitivity was measured as surviving fraction following irradiation with 2 Gy (SF2 by clonogenic assay. Differential gene expression between radiosensitive and radioresistant cell lines (SF2 median was investigated using Affymetrix GeneChip Exon 1.0ST (cervix or U133A Plus2 (head and neck arrays. There were differences within cell line cohorts relating to tissue of origin reflected by expression of the stratified epithelial marker p63. Of 138 genes identified as being associated with SF2, only 2 (1.4% were congruent between the cervix and head and neck carcinoma cell lines (MGST1 and TFPI, and these did not partition the published NCI-60 cell lines based on SF2. There was variable success in applying three published radiosensitivity signatures to our cohorts. One gene signature, originally trained on the NCI-60 cell lines, did partially separate sensitive and resistant cell lines in all three cell line datasets. The findings do not confirm our hypothesis but suggest that a common transcriptional signature can reflect the radiosensitivity of tumours of heterogeneous origins.

  6. Design, synthesis, broad-spectrum antiproliferative activity, and kinase inhibitory effect of triarylpyrazole derivatives possessing arylamides or arylureas moieties.

    Science.gov (United States)

    Gamal El-Din, Mahmoud M; El-Gamal, Mohammed I; Abdel-Maksoud, Mohammed S; Yoo, Kyung Ho; Oh, Chang-Hyun

    2016-08-25

    A novel series of 1,3,4-triarylpyrazole derivatives possessing terminal arylamide or arylurea terminal moieties has been designed and synthesized. Their in vitro antiproliferative activities were investigated against a panel of 58 cell lines of nine different cancer types at the NCI, USA. The urea analogues 2b, 2c, and 2f as well as the amide derivatives 3e and 3f exerted the highest mean % inhibition values over the 58 cell line panel at 10 μM, and thus were further tested in 5-dose testing mode to determine their GI50, TGI, and LC50 values. The above mentioned compounds have shown stronger antiproliferative activities in terms of potency and efficacy upon comparing their results with Sorafenib as a reference compound. Among them, compounds 2c and 2f possessing 3,4-dichlorophenylurea terminal moiety showed the highest mean %inhibition value of about 99.85 and 104.15% respectively over the 58-cell line panel at 10 μM concentration. Also compounds 2b, 3e, and 3f exhibited mean % inhibition over 80% at 10 μM concentration. The GI50 value of compound 3e over K-562 cancer cell line was 0.75 μM. Accordingly, compound 2f was screened over seven kinases at a single-dose concentration of 10 μM to profile its kinase inhibitory activity. Interestingly, the compound showed highly inhibitory activities (90.44% and 87.71%) against BRAF (V600E) and RAF1 kinases, respectively. Its IC50 value against BRAF (V600E) was 0.77 μM. Compounds 2b, 2c, 2f, 3e, and 3f exerted high selectivity towards cancer cell lines than L132 normal lung cells. PMID:27155467

  7. Development of a cell line from Echinococcus granulosus germinal layer.

    Science.gov (United States)

    Albani, Clara María; Cumino, Andrea Carina; Elissondo, María Celina; Denegri, Guillermo María

    2013-10-01

    In vitro culture of parasitic helminths provides an important tool to study cell regeneration and physiology, as well as for molecular biology and genetic engineering studies. In the present study, we established in vitro propagation of cells from Echinococcus granulosus germinal cyst layer. E. granulosus germinal cells grew beyond 100 passages and showed no signs of reduced proliferation capacity. Microscopic analysis revealed that cells grew both attached to the substrate and in suspension, forming three-dimensional structures like mammalian stem cell aggregates. Examination of the chromosome number of attached germinal cells showed a high degree of heteroploidy, suggesting the occurrence of transformation during culture. Monolayer cells survived