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Sample records for possesses significant anticancer

  1. The epistemological significance of possession entering the DSM.

    Science.gov (United States)

    Stephenson, Craig

    2015-09-01

    The discourse of the American Psychiatric Association's DSM reflects the inherently dialogic or contradictory nature of its stated mandate to demonstrate both 'nosological completeness' and cultural 'inclusiveness'. Psychiatry employs the dialogic discourse of the DSM in a one-sided, positivistic manner by identifying what it considers universal mental disease entities stripped of their cultural context. In 1992 the editors of the Diagnostic and Statistical Manual of Mental Disorders proposed to introduce possession into their revisions. A survey of the discussions about introducing 'possession' as a dissociative disorder to be listed in the DSM-IV indicates a missed epistemological break. Subsequently the editors of the DSM-5 politically 'recuperated' possession into its official discourse, without acknowledging the anarchic challenges that possession presents to psychiatry as a cultural practice. © The Author(s) 2015.

  2. LEGAL SIGNIFICANCE AND PROTECTION OF POSSESSION IN THE REPUBLIC OF MACEDONIA

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    Vojo Belovski

    2015-04-01

    Full Text Available In this paper it will be discussed the legal significance and protection of possession in the Republic of Macedonia. Below it will be listed the kinds of possession, and finally the rules for possession termination will be explained. The possession is an indicator that the person who rules one item is also a right holder of that item. The possession itself occurs in two types specially authorized by a law and pure factual power behind which stands no right. The possession enjoys legal protection. Below in the paper it is processed the judicial protection of the possession which is given based on complaint for disturbance of possession and action to recover the possession. The important thing at the judicial protection is that the rulers’ protection is given to the last actual possession of the item, but it is not disputed the right of possession. Further in this paper it is included the protection of indirect possession where a complaint can be made by the indirect holder of the item, the judicial protection of possessory, possession protection of the heirs and permitted self – help for unauthorized harassment and revoking of the possession. With respect to the termination of the actual power of the item, listed and processed are the ways when the item failed, when the item was lost, when it is obvious that it won’t be returned, when the ruler had freely left it and when the item is not taken from him and the ruler hasn’t realized the right to possession.

  3. Consensus-based evaluation of clinical significance and management of anticancer drug interactions

    NARCIS (Netherlands)

    Jansman, F.G.A.; Reyners, A.K.L.; van Roon, E.N.; Smorenburg, C.H.; Helgason, H.H.; le Comte, M.; Wensveen, B.M.; van den Tweel, A.M.A.; de Blois, M.; Kwee, W.; Kerremans, A.L.; Brouwers, J.R.B.J.

    Background: Anticancer drug interactions can affect the efficacy and toxicity of anticancer treatment and that of the interacting drugs. However, information on the significance, prevention, and management of these interactions is currently lacking. Objective: The purpose of this study was to assess

  4. Development and evaluation of tocopherol-rich argan oil-based nanoemulsions as vehicles possessing anticancer activity.

    Science.gov (United States)

    Jordan, Melanie; Nayel, Amy; Brownlow, Bill; Elbayoumi, Tamer

    2012-12-01

    In recent years, diverse nanoemulsion vehicles (NEs) have been developed with vast potential for improving therapeutic index of clinically approved and experimental drugs. Using oils rich in omega-3 and omega-6 polyunsaturated fatty acids (PUFA), several promising nanoemulsion formulations have been developed recently for oral and systemic administration. The aim of our present work is to successfully develop and characterize optimized nanoemulsion platform, using the PUFA-rich argan oil that contain several important anti-inflammatory and antimitotic natural components. Using various emulsifying mixtures of polyethoxylated solutol HS-15 and polyethyleneglucol Vitamin E succinyl ester (TPGS), to form different NEs showing extended shelf-life stability. The physicochemical properties of prototype argan NEs were analyzed and utilizing a 32 full factorial design, followed by biocompatibility screen, using normal vascular myocytes and areolar fibroblasts. While 90-180 day stability of NEs correlated with TPGS:solutol surfactant blend ratios, adverse effects on integrity of test cultures were only noted at high TPGS content in the emulsifier system, exceeding 80%. Finally, the anti-proliferative efficacy of selected stable and acceptably biocompatible nanoscale TPGS-emulsified argan oil formulations was investigated using murine breast and colon carcinoma cells. The IC50 values of the combination of argan oil and TPGS (40-80% wt of emulsifiers) were 5-9 folds lower compared to TPGS-free and argan-oil free control NEs. Argan oil NE, stabilized with Vitamin E TPGS and solutol HS mixtures, demonstrated significant pro-apoptotic effect on both test cancer cell lines, indicating built-in anticancer properties for such NE platform, potentially enhancing overall antineoplastic effects of incorporated candidate chemotherapeutic agents.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-04

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

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

    International Nuclear Information System (INIS)

    Jeong, Jin Boo; Lee, Seong-Ho

    2013-01-01

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

  7. Green tea phytocompounds as anticancer: A review

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    Najeeb Ullah

    2016-04-01

    Full Text Available Green tea is universally considered significant and its benefits have been experimentally explored by researchers and scientists. Anticancer potential of green tea has been completely recognized now. Green tea contains anti-cancerous constituents and nutrients that have powerful remedial effects. By using electronic data base (1998–2015, different compounds in green tea possessing anticancer activity including epigallocatechin-3-gallate, paclitaxel and docetaxel combinations, ascorbic acid, catechins, lysine, synergistic arginine, green tea extract, proline, and green tea polyphenols has been reported. Green tea extracts exhibited remedial potential against cancer of lung, colon, liver, stomach, leukemic cells, prostate, breast, human cervical cells, head, and neck. For centuries, green tea has been utilized as medicine for therapeutic purposes. It originated in China and extensively used in Asian countries for blood pressure depression and as anticancer medicine. Green tea has therapeutic potential against many diseases such as lowering of blood pressure, Parkinson’s disease, weight loss, esophageal disease, skin-care, cholesterol, Alzheimer’s disease and diabetes.

  8. The protection of possession

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    Popov Danica

    2011-01-01

    Full Text Available Protection in disputes for the protection of possession can be attained through the following actions a for dispossession (interdictum recuperande possessionis and b with an action for the disturbance of possession (interdictum retinendae possessionis. The general feature of these disputes is that there is only discussion on the facts and not a legal matters. Subject matter jurisdiction for the resolution of such disputes belongs to the court of general jurisdiction, while the dispute itself is a litigation. The special rule of proceedings of action for disturbance are: provisionality of the protection of possession; urgency in proceedings; initiation of the proceedings; limiting of objection; prescribing temporary measures; rendering a ruling in the form of order; appeals which may be filed within a short deadline and which does not have suspensive effect (do not delay the execution of the order; revision is not allowed etc.

  9. Individual ball possession in soccer.

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    Daniel Link

    Full Text Available This paper describes models for detecting individual and team ball possession in soccer based on position data. The types of ball possession are classified as Individual Ball Possession (IBC, Individual Ball Action (IBA, Individual Ball Control (IBC, Team Ball Possession (TBP, Team Ball Control (TBC und Team Playmaking (TPM according to different starting points and endpoints and the type of ball control involved. The machine learning approach used is able to determine how long the ball spends in the sphere of influence of a player based on the distance between the players and the ball together with their direction of motion, speed and the acceleration of the ball. The degree of ball control exhibited during this phase is classified based on the spatio-temporal configuration of the player controlling the ball, the ball itself and opposing players using a Bayesian network. The evaluation and application of this approach uses data from 60 matches in the German Bundesliga season of 2013/14, including 69,667 IBA intervals. The identification rate was F = .88 for IBA and F = .83 for IBP, and the classification rate for IBC was κ = .67. Match analysis showed the following mean values per match: TBP 56:04 ± 5:12 min, TPM 50:01 ± 7:05 min and TBC 17:49 ± 8:13 min. There were 836 ± 424 IBC intervals per match and their number was significantly reduced by -5.1% from the 1st to 2nd half. The analysis of ball possession at the player level indicates shortest accumulated IBC times for the central forwards (0:49 ± 0:43 min and the longest for goalkeepers (1:38 ± 0:58 min, central defenders (1:38 ± 1:09 min and central midfielders (1:27 ± 1:08 min. The results could improve performance analysis in soccer, help to detect match events automatically, and allow discernment of higher value tactical structures, which is based on individual ball possession.

  10. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  11. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  12. Melatonin Anticancer Effects: Review

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    Luigi Di Bella

    2013-01-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine, MLT, the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate. The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation. All these particular characteristics suggest the use of MLT in oncological diseases.

  13. Anticancer peptides from bacteria

    OpenAIRE

    Tomasz M. Karpiński; Anna K. Szkaradkiewicz

    2013-01-01

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

  14. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński

    2013-08-01

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

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

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    Md. Azizur Rahman

    2015-03-01

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

  16. Anticancer Activity of Amauroderma rude

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

    2013-01-01

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

  17. Anticancer activity of Amauroderma rude.

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    Chunwei Jiao

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

  18. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

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    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast

  19. Anticancer properties of brassinosteroids

    Czech Academy of Sciences Publication Activity Database

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

    2007-01-01

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

  20. Anticancer drugs during pregnancy.

    Science.gov (United States)

    Miyamoto, Shingo; Yamada, Manabu; Kasai, Yasuyo; Miyauchi, Akito; Andoh, Kazumichi

    2016-09-01

    Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. The qualified possession turn into ownership

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    Popov Danica

    2011-01-01

    Full Text Available Possession is prima facie evidence of ownership. Possession is ninetents of the law, means that possession is good against all other, except the true owner. The possession ripens into ownership if it is qualified and by effluxion of time. In Serbian law there are two kinds of adverse possession ripens into ownership. The first one is named ordinary and second one extraordinary adverse possession. Ordinary possession need to be legal, conscientious and genuine. Extraordinary possession is only conscientious, but in a wide sense. Adverse possession destroys the title of the owner and vests it in possessor. An occupation of land inconsistent with the right of the true owner: the possession of those against whom a right action has accured to the true owner. It is actual possession in the absence of possession by the rightful owner and without lawful title. If the adverse possession continues, the effect at the expiration of the prescribed period is that not only the remedy but the title of former owner is extinguished. The person in adverse possession gains a new possessory title which cannot, normally exceed in extent of duration the interest of the former owner.

  2. Anticancer Properties of Capsaicin Against Human Cancer.

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    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

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

  3. Anticancer Properties of Lamellarins

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    Christian Bailly

    2015-02-01

    Full Text Available In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids.

  4. Magnetic polymer nanospheres for anticancer drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    JurIkova, A; Csach, K; Koneracka, M; Zavisova, V; Tomasovicova, N; Lancz, G; Kopcansky, P; Timko, M; Miskuf, J [Institute of Experimental Physics, Slovak Academy of Sciences, 040 01 Kosice (Slovakia); Muckova, M, E-mail: akasard@saske.s [Hameln rds a.s., 900 01 Modra (Slovakia)

    2010-01-01

    Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

  5. and in anticancer therapy

    Directory of Open Access Journals (Sweden)

    Monika Toma

    2014-09-01

    Full Text Available Nowadays, cancer and anticancer therapy are increasingly mentioned topics. Groups of researchers keep looking for a tool that will specifically and efficiently eliminate abnormal cells without any harm for the normal ones. Such method entails the reduction of therapy’s side effects, thus also improving patient’s recovery. Discovery of synthetic lethality has become a new hope to create effective, personalized therapy of cancer. Researchers noted that pairs of simultaneously mutated genes can lead to cell death, whereas each gene from that pair mutated individually does not result in cell lethality. Cancer cells accumulate numerous changes in their genetic material. By defining the pairs of genes interacting in cell pathways we are able to identify a potential anticancer therapy. It is believed that such a process has evolved to create cell resistance for a single gene mutation. Proper functioning of a pathway is not dependent on a single gene. Such a solution, however, also led to the evolution of multifactorial diseases such as cancer. Research techniques using iRNA, shRNA or small molecule libraries allow us to find genes that are connected in synthetic lethality interactions. Synthetic lethality may be applied not only as an anticancer therapy but also as a tool for identifying the functions of recently recognized genes. In addition, studying synthetic lethality broadens our understanding of the molecular mechanisms governing cancer cells, which should be helpful in designing highly effective personalized cancer therapies.

  6. Constitutional Law: Right of Privacy--Possession of Marijuana

    Science.gov (United States)

    Rohrer, David E.

    1976-01-01

    The Alaska Supreme Court in Ravin v. State accepted the defendant's contention that the prohibition of possession of marihuana infringed on his constitutional right to privacy. The significance of the case is discussed. (LBH)

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

    Tanih, Nicoline Fri; Ndip, Roland Ndip

    2013-01-01

    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. PMID:23576913

  9. Tomato leaves methanol extract possesses antiinflammatory activity ...

    African Journals Online (AJOL)

    Recently, the leaves of tomato plant that contained several active compounds including alkaloid, steroid and flavanoid has been used for the treatment of variety of diseases and as anti-cancer, antioxidant and anti-gout. Although, a number of pharmacological properties have already been demonstrated, the ...

  10. Anticancer Activity of Bacterial Proteins and Peptides.

    Science.gov (United States)

    Karpiński, Tomasz M; Adamczak, Artur

    2018-04-30

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

  11. 50 CFR 648.164 - Possession restrictions.

    Science.gov (United States)

    2010-10-01

    ... Atlantic Bluefish Fishery § 648.164 Possession restrictions. (a) No person shall possess more than 15 bluefish in, or harvested from, the EEZ unless that person is the owner or operator of a fishing vessel issued a bluefish commercial permit or is issued a bluefish dealer permit. Persons aboard a vessel that...

  12. Trial Watch: Anticancer radioimmunotherapy.

    Science.gov (United States)

    Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-09-01

    Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in

  13. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  14. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    Yang, Danbo; Yu, Lei; Van, Sang

    2010-01-01

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  15. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  16. POSSESSION, REVIEW FROM CULTURAL AND PSYCHIATRY

    Directory of Open Access Journals (Sweden)

    Ni Ketut Sri Diniari

    2013-03-01

    Full Text Available Possession is a culture related syndrome, commonly found in Indonesia including Bali. We can see this event in religion and cultural ceremony and at other times at school, home, and in society. This syndrome consist of temporary loss of self identification and environment awareness; in several events a person acts as if he/she was controlled by other being, magic force, spirit or ‘other forces’. There are still several different opinions about trance-possession, whether it is related to certain culture or is a part of mental disorder. DSM-IV-TR and PPDGJ-III defined trance-possession as mental disorder (dissociative for involuntary possession, if it is not a common activity, and if it is not a part of religion or cultural event. (MEDICINA 2012;43:37-40.

  17. Subself theory and reincarnation/possession.

    Science.gov (United States)

    Lester, David

    2004-12-01

    A subself model of the mind is used to account for multiple personality, possession, the spirit controls of mediums, reincarnation, and the auditory hallucinations of schizophrenics, with suggestions for empirical research.

  18. The Impact of Banning Juvenile Gun Possession.

    OpenAIRE

    Marvell, Thomas B

    2001-01-01

    A 1994 federal law bans possession of handguns by persons under 18 years of age. Also in 1994, 11 states passed their own juvenile gun possession bans. Eighteen states had previously passed bans, 15 of them between 1975 and 1993. These laws were intended to reduce homicides, but arguments can be made that they have no effect on or that they even increase the homicide rate. This paper estimates the laws' impacts on various crime measures, primarily juvenile gun homicide victimizations and suic...

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-02-01

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

  1. Developments in platinum anticancer drugs

    Science.gov (United States)

    Tylkowski, Bartosz; Jastrząb, Renata; Odani, Akira

    2018-01-01

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

  2. Carboxylate derivatives of tributyltin (IV) complexes as anticancer and antileishmanial agents.

    Science.gov (United States)

    Waseem, Durdana; Butt, Arshad Farooq; Haq, Ihsan-Ul; Bhatti, Moazzam Hussain; Khan, Gul Majid

    2017-04-04

    Tributyltin (IV) compounds are promising candidates for drug development. In the current study, we evaluated in-vitro and in-silico profile of carboxylate derivatives of tributyltin (IV) complexes. ADMET and drug-likeliness properties were predicted using MetaPrint2D React, preADMET, SwissADME and Molsoft tools. SwissTargetPrediction predicted molecular targets for compounds. In-vitro bioactivity was evaluated by quantifying cytotoxicity against HepG2, THP-1 cell lines, isolated lymphocytes and leishmania promastigotes as well as measuring protein kinase (PK) inhibition activity. Results indicate partial compliance of compounds with drug-likeliness rules. Ch-409 complies with WDI and Lipinski rules. ADMET profile prediction shows strong plasma protein binding except for Ch-409, low to high GI absorption and BBB penetration (C brain /C blood  = 0.942-11; caco-2 cells permeability 20.13-26.75 nm/sec), potential efflux by P-glycoprotein, metabolism by CYP3A4, medium inhibition of hERG, mutagenicity and capacity to be detoxified by glutathionation and glucuronidation. Molecular targets include proteases, enzymes, membrane receptors, transporters and ion channels where Ch-409 targets membrane receptors only. Compounds are significantly (p tributyltin (IV) complexes possess significant antileishmanial and cytotoxic potential. These are promising compounds for the development of antileishmanial and anticancer drugs. Graphical Abstract Carboxylate derivatives of tributyltin (IV) complexes as anticancer and antileishmanial agents.

  3. Acupuncture as anticancer treatment?

    Directory of Open Access Journals (Sweden)

    Paulina Frączek

    2017-01-01

    Full Text Available The mystery of Traditional Chinese Medicine has been attracting people for years. Acupuncture, ranked among the most common services of Complementary and Alternative Medicine, has recently gained a lot of interest in the scientific world. Contemporary researchers have been continuously trying to shed light on its possible mechanism of action in human organism. Numerous studies pertaining to acupuncture’s application in cancer symptoms or treatment-related side effects management have already been published. Moreover, since the modern idea of acupuncture’s immunomodulating effect seems to be promising, scientists have propounded a concept of its potential application as part of direct anti-tumor therapy. In our previous study we summarized possible use of acupuncture in management of cancer symptoms and treatment-related ailments, such as chemotherapy-induced nausea and vomiting, pain, xerostomia, vasomotor symptoms, neutropenia, fatigue, anxiety, insomnia, lymphoedema after mastectomy and peripheral neuropathy. This article reviews the studies concerning acupuncture as a possible tool in modern anticancer treatment.

  4. Metabolic immune restraints: implications for anticancer vaccines.

    Science.gov (United States)

    Mocellin, Simone

    2010-01-01

    Metabolic immune restraints belong to a highly complex network of molecular mechanisms underlying the failure of naturally occurring and therapeutically induced immune responses against cancer. In the light of the disappointing results yielded so far with anticancer vaccines in the clinical setting, the dissection of the cascade of molecular events leading to tumor immune escape appears the most promising way to develop more effective immunotherapeutic strategies. Here we review the significant advances recently made in the understanding of the tumor-specific metabolic features that contribute to keep malignant cells from being recognized and destroyed by immune effectors. These mechanistic insights are fostering the development of rationally designed therapeutics aimed to revert the immunosuppressive circuits and thus to enhance the effectiveness of anticancer vaccines.

  5. Isocorydine Derivatives and Their Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Mei Zhong

    2014-08-01

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

  6. Medicinal plants combating against cancer--a green anticancer approach.

    Science.gov (United States)

    Sultana, Sabira; Asif, Hafiz Muhammad; Nazar, Hafiz Muhammad Irfan; Akhtar, Naveed; Rehman, Jalil Ur; Rehman, Riaz Ur

    2014-01-01

    Cancer is the most deadly disease that causes the serious health problems, physical disabilities, mortalities, and morbidities around the world. It is the second leading cause of death all over the world. Although great advancement have been made in the treatment of cancer progression, still significant deficiencies and room for improvement remain. Chemotherapy produced a number of undesired and toxic side effects. Natural therapies, such as the use of plant-derived products in the treatment of cancer, may reduce adverse and toxic side effects. However, many plants exist that have shown very promising anticancer activities in vitro and in vivo but their active anticancer principle have yet to be evaluated. Combined efforts of botanist, pharmacologist and chemists are required to find new lead anticancer constituent to fight disease. This review will help researchers in the finding of new bioactive molecules as it will focus on various plants evaluated for anticancer properties in vitro and in vivo.

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

    Science.gov (United States)

    Ganogpichayagrai, Aunyachulee; Palanuvej, Chanida; Ruangrungsi, Nijsiri

    2017-01-01

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

  8. Possession divestment by sales in later life.

    Science.gov (United States)

    Ekerdt, David J; Addington, Aislinn

    2015-08-01

    Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers' capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation. Among this group, three-quarters of the households downsized by selling some belongings. Informal sales seemed the least fraught of all strategies, estate sales had mixed reviews, and garage sales were recalled as laborious. Sellers' efforts were eased by social relations and social networks as helpers and buyers came forward. As selling proceeded, sentiment about possessions waned as their materiality and economic value came to the fore, easing their detachment from the household. Possession selling is challenging because older adults are limited in the knowledge, skills, and efforts that they can apply to the recommodification of their belongings. Selling can nonetheless be encouraged as a divestment strategy as long as the frustrations and drawbacks are transparent, and the goal of ridding is kept in view. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Apoptin towards safe and efficient anticancer therapies.

    Science.gov (United States)

    Backendorf, Claude; Noteborn, Mathieu H M

    2014-01-01

    The chicken anemia virus derived protein apoptin harbors cancer-selective cell killing characteristics, essentially based on phosphorylation-mediated nuclear transfer in cancer cells and efficient cytoplasmic degradation in normal cells. Here, we describe a growing set of preclinical experiments underlying the promises of the anti-cancer potential of apoptin. Various non-replicative oncolytic viral vector systems have revealed the safety and efficacy of apoptin. In addition, apoptin enhanced the oncolytic potential of adenovirus, parvovirus and Newcastle disease virus vectors. Intratumoral injection of attenuated Salmonella typhimurium bacterial strains and plasmid-based systems expressing apoptin resulted in significant tumor regression. In-vitro and in-vivo experiments showed that recombinant membrane-transferring PTD4- or TAT-apoptin proteins have potential as a future anticancer therapeutics. In xenografted hepatoma and melanoma mouse models PTD4-apoptin protein entered both cancer and normal cells, but only killed cancer cells. Combinatorial treatment of PTD4-apoptin with various (chemo)therapeutic compounds revealed an additive or even synergistic effect, reducing the side effects of the single (chemo)therapeutic treatment. Degradable polymeric nanocapsules harboring MBP-apoptin fusion-protein induced tumor-selective cell killing in-vitro and in-vivo and revealed the potential of polymer-apoptin protein vehicles as an anticancer agent.Besides its direct use as an anticancer therapeutic, apoptin research has also generated novel possibilities for drug design. The nuclear location domains of apoptin are attractive tools for targeting therapeutic compounds into the nucleus of cancer cells. Identification of cancer-related processes targeted by apoptin can potentially generate novel drug targets. Recent breakthroughs important for clinical applications are reported inferring apoptin-based clinical trials as a feasible reality.

  10. Functional evaluation of synthetic flavonoids and chalcones for potential antiviral and anticancer properties.

    Science.gov (United States)

    Mateeva, Nelly; Eyunni, Suresh V K; Redda, Kinfe K; Ononuju, Ucheze; Hansberry, Tony D; Aikens, Cecilia; Nag, Anita

    2017-06-01

    Flavonoids, stilbenes, and chalcones are plant secondary metabolites that often possess diverse biological activities including anti-inflammatory, anti-cancer, and anti-viral activities. The wide range of bioactivities poses a challenge to identify their targets. Here, we studied a set of synthetically generated flavonoids and chalcones to evaluate for their biological activity, and compared similarly substituted flavonoids and chalcones. Substituted chalcones, but not flavonoids, showed inhibition of viral translation without significantly affecting viral replication in cells infected with hepatitis C virus (HCV). We suggest that the chalcones used in this study inhibit mammalian target of rapamycin (mTOR) pathway by ablating phosphorylation of ribosomal protein 6 (rps6), and also the kinase necessary for phosphorylating rps6 in Huh7.5 cells (pS6K1). In addition, selected chalcones showed inhibition of growth in Ishikawa, MCF7, and MDA-MB-231 cells resulting an IC 50 of 1-6µg/mL. When similarly substituted flavonoids were used against the same set of cancer cells, we did not observe any inhibitory effect. Together, we report that chalcones show potential for anti-viral and anti-cancer activities compared to similarly substituted flavonoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Synthesis, structure, computational and in-silico anticancer studies of N,N-diethyl-N‧-palmitoylthiourea

    Science.gov (United States)

    Asegbeloyin, Jonnie Niyi; Oyeka, Ebube Evaristus; Okpareke, Obinna; Ibezim, Akachukwu

    2018-02-01

    A new potential ONS donor ligand N,N-diethyl-N‧-palmitoylthiourea (PACDEA) with the molecular formular C21H42N2OS has been synthesized and characterized by ESI-MS, UV, FTIR 1H and 13C NMR spectroscopy and single X-ray crystallography. The asymmetric molecules crystallized in the centrosymmetric structure of monoclinic crystal system with space group P21/c. In the crystal structure of the compound, molecules are linked in a continuous chain by intermolecular Nsbnd H⋯Odbnd C hydrogen bonds, which stabilized the crystal structure. The palmitoyl moiety and N (2)-ethyl group lie on a plane, while the thiocarbonyl moiety is twisted and lying othorgonal to the plane. Non-covalent interaction (NCI) analysis on the hydrogen bonded solid state structure of the molecule revealed the presence of a significant number of non-covalent interactions including intermolecular hydrogen bonding interactions, Csbnd Hsbnd -lone pair interactions, weak Van der Waals interactions, and steric/ring closure interactions. The NCI analysis also showed the presence of intramolecular stabilizing Csbnd H⋯Odbnd C and Csbnd H⋯Sdbnd C interactions. Docking simulation revealed that the compound interacted favourably with ten selected validated anticancer drug targets, which is an indication that the compound could possess some anticancer properties.

  12. THE ROLE OF RED PIGMENT PRODIGIOSIN FROM BACTERIA OF EARTHWORM GUT AS AN ANTICANCER AGENT

    Directory of Open Access Journals (Sweden)

    Sruthy P.B.

    2014-12-01

    Full Text Available Earthworms are the most ancient invertebrate animals on earth which can be used as a good source of pharmaceutical compounds. A study was carried out to find out the distribution of microorganisms in the gut of earthworm, Eudrilus eugeniae. Significant number of microbial populations in the gut of earthworm was observed and it was gradually increased from the initial day to final day of composting. Pigmented colonies of bacteria from earthworm gut were selectively isolated, the pigment was extracted from the culture broth and a presumptive test was carried out for the confirmation of prodigiosin. The pigment component was separated using thin layer chromatography and the structural elucidation of the compound was performed using U.V. spectroscopy. The inhibitory effect of prodigiosin on bacterial pathogens was studied and the results confirmed the antibacterial activity against gram positive bacteria. The anticancer activity of the prodigiosin pigment was evaluated under in vitro conditions against the breast cancer cell lines and it was observed that prodigiosin induced the apoptosis in MCF-7 cell lines in a dose dependent manner. Then the potential isolate was subjected to morphological and biochemical analysis and it was confirmed that the colonies were of Serratia marcescens. The results obtained from the present study indicated that earthworm gut is promising and could be a vital source of habitat possessing antimicrobial and anticancer activity.

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

    Directory of Open Access Journals (Sweden)

    Iqbal Asif

    2011-09-01

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

  14. The Failed Image and the Possessed

    DEFF Research Database (Denmark)

    Suhr, Christian

    2015-01-01

    This article asks if the recurrent queries regarding the value of images in visual anthropology could find new answers by exploring responses to visual media in neo-orthodox Islam. It proposes that the visual display of the photographic image shares a curious resemblance to the bodies of people...... possessed by invisible spirits called jinn. The image as a failed example or model of reality works like the possessed body as an amplifier of invisibility pointing towards that which cannot be seen, depicted visually, or represented in writing. This suggests a negative epistemology in which images obtain...

  15. Ganoderma lucidum Polysaccharides as An Anti-cancer Agent.

    Science.gov (United States)

    Sohretoglu, Didem; Huang, Shile

    2017-11-13

    The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

    Science.gov (United States)

    Stoika, R.; Boiko, N.; Senkiv, Y.; Shlyakhtina, Y.; Panchuk, R.; Finiuk, N.; Filyak, Y.; Bilyy, R.; Kit, Y.; Skorohyd, N.; Klyuchivska, O.; Zaichenko, A.; Mitina, N.; Ryabceva, A.

    2013-04-01

    We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

  17. Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

    International Nuclear Information System (INIS)

    Stoika, R; Boiko, N; Panchuk, R; Filyak, Y; Senkiv, Y; Finiuk, N; Shlyakhtina, Y; Bilyy, R; Kit, Y; Skorohyd, N; Klyuchivska, O; Zaichenko, A; Mitina, N; Ryabceva, A

    2013-01-01

    We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

  18. Anticancer Efficacy of Polyphenols and Their Combinations

    Directory of Open Access Journals (Sweden)

    Aleksandra Niedzwiecki

    2016-09-01

    Full Text Available Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract with vitamin C, amino acids and other micronutrients (EPQ demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion

  19. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review.

    Science.gov (United States)

    Gan, Ren-You; Li, Hua-Bin; Sui, Zhong-Quan; Corke, Harold

    2018-04-13

    Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.

  20. Digital possessions after a romantic break up

    NARCIS (Netherlands)

    Herron, Daniel; Moncur, Wendy; van den Hoven, Elise

    2016-01-01

    With technology becoming more pervasive in everyday life, it is common for individuals to use digital media to support the enactment and maintenance of romantic relationships. Partners in a relationship may create digital possessions frequently. However, after a relationship ends, individuals

  1. Polypharmacology of Approved Anticancer Drugs.

    Science.gov (United States)

    Amelio, Ivano; Lisitsa, Andrey; Knight, Richard A; Melino, Gerry; Antonov, Alexey V

    2017-01-01

    The major drug discovery efforts in oncology have been concentrated on the development of selective molecules that are supposed to act specifically on one anticancer mechanism by modulating a single or several closely related drug targets. However, a bird's eye view on data from multiple available bioassays implies that most approved anticancer agents do, in fact, target many more proteins with different functions. Here we will review and systematize currently available information on the targets of several anticancer drugs along with revision of their potential mechanisms of action. Polypharmacology of the current antineoplastic agents suggests that drug clinical efficacy in oncology can be achieved only via modulation of multiple cellular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. POSSESSION VERSUS POSITION: STRATEGIC EVALUATION IN AFL

    Directory of Open Access Journals (Sweden)

    Darren M. O'Shaughnessy

    2006-12-01

    Full Text Available In sports like Australian Rules football and soccer, teams must battle to achieve possession of the ball in sufficient space to make optimal use of it. Ultimately the teams need to score, and to do that the ball must be brought into the area in front of goal - the place where the defence usually concentrates on shutting down space and opportunity time. Coaches would like to quantify the trade-offs between contested play in good positions and uncontested play in less promising positions, in order to inform their decision-making about where to put their players, and when to gamble on sending the ball to a contest rather than simply maintain possession. To evaluate football strategies, Champion Data has collected the on-ground locations of all 350,000 possessions and stoppages in the past two seasons of AFL (2004, 2005. By following each chain of play through to the next score, we can now reliably estimate the scoreboard "equity" of possessing the ball at any location, and measure the effect of having sufficient time to dispose of it effectively. As expected, winning the ball under physical pressure (through a "hard ball get" is far more difficult to convert into a score than winning it via a mark. We also analyse some equity gradients to show how getting the ball 20 metres closer to goal is much more important in certain areas of the ground than in others. We conclude by looking at the choices faced by players in possession wanting to maximise their likelihood of success

  3. Comparative investigation of the free radical scavenging potential and anticancer property of Diospyros blancoi (Ebenaceae

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Khan

    2016-05-01

    Conclusions: Our results indicate that Diospyros blancoi stem bark had the significant highest antioxidant and free radical scavenging properties as well as moderate anticancer activity. Hence, we assume that the anticancer activity of this plant can be, at least in part, attributed to its content in phenolic compounds as well as its significant free radical scavenging properties.

  4. Taking Possession: Rituals, Space and Authority

    Directory of Open Access Journals (Sweden)

    Jennifer Mara DeSilva

    2016-12-01

    Full Text Available In early modern Europe authority over communities, both people and spaces, was visualized through ritual gestures and processions. Communities gathered to witness ceremonial entries that drew on accepted forms of gestures and speech identifying individuals and articulating their place in the urban power relationship. Ceremonial entries by rulers, ambassadors, bishops, and other office-holders drew on ritual acts projecting messages of possession in order to establish reputations of prestige and authority. This introductory essay draws on cultural anthropology and recent historiography to build a framework for understanding rituals of possession that went beyond the tradition triumphal entry to incorporate substitutes, new modes of prestigious display, and attend to conflicts. By “taking possession” of communities, offices, and spaces using accepted ritual forms, early moderns initiated conversations about authority and power that were far more flexible in their scope, practice, and participants than expected.

  5. From distress to disease: a critique of the medicalisation of possession in DSM-5.

    Science.gov (United States)

    Padmanabhan, Divya

    2017-12-01

    This paper critiques the category of possession-form dissociative identity disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) published in 2013 by the American Psychiatric Association (APA). The DSM as an index of psychiatry pathologises possession by categorising it as a form of dissociative identity disorder. Drawing upon ethnographic fieldwork, this paper argues that such a pathologisation medicalises possession, which is understood as a non-pathological condition in other contexts such as by those individuals who manifest possession at a temple in Kerala, South India. Through medicalising and further by creating distinctions between acceptable and pathological possession, the DSM converts a form of distress into a disease. This has both conceptual and pragmatic implications. The temple therefore becomes reduced to a culturally acceptable site for the manifestation of a mental illness in a form that is culturally available and possession is explained solely through a biomedical framework, denying alternative conceptualisations and theories which inform possession. By focussing on the DSM-5 classification of possession and the limitations of such a classification, this paper seeks to posit an alternative conceptualisation of possession by engaging with three primary areas which are significant in the DSM categorisation of possession: the DSM's conceptualisation of self in the singular, the distinction between pathological and non-pathological forms of possession, and the limitations of the DSM's equation of the condition of possession with the manifestation of possession. Finally, the paper briefly highlights alternative conceptualisations of possession, which emerged from the perspective of those seeking to heal possession at the Chottanikkara temple.

  6. Dynamics of the spirit possession phenomenon in Eastern Tanzania

    Directory of Open Access Journals (Sweden)

    Marja-Liisa Swantz

    1976-01-01

    Full Text Available The discussion on the spirit possession phenomenon is related in this study to the more general question of the role of religious institutions as part in the development process of a people living in a limited geographical area of a wider national society. It is assumed that religion, like culture in general, has its specific institutional forms as result of the historical development of a society, but at the same time religion is a force shaping that history. People's cultural resources influence their social and economic development and form a potential creative element in it'. Some of the questions to be asked are: "How are specific religious practices related to the dynamics of change in the societies in question? What is the social and religious context in which the spirit possession phenomenon occurs in them? What social and economic relations get their expression in them? To what extent is spirit possession in this case a means of exerting values and creatively overcoming a crisis or conflict which the changing social and economic relations impose on the people? The established spirit possession cults are here seen as the institutional forms of religious experience. At the same time it becomes evident that there is institutionalization in process as well as deinstitutionalization of spirit possession where it occurs outside established institutional forms. Institution is taken as a socially shared form of behaviour the significance of which is commonly recognized by those who share it. By the term spirit possession cult is meant a ritual form of spirit possession of a group which is loosely organized and without strict membership. The context of the study is four ethnic groups in Eastern Tanzania, near the coast of the Indian Ocean. The general theme of the project is The Role of Culture in the Restructuring of Tanzanian Rural Areas. The restructuring refers to a villagisation programme carried out in the whole country. People are being

  7. Cytogenotoxic effects of two potential anticancer Ruthenium(III Schiff Bases complexes

    Directory of Open Access Journals (Sweden)

    Izet Eminovic

    2016-10-01

    Full Text Available Introduction: Treatment of cancer has been subject of great interest. Researchers are continuously searching for new medicines. In this sense, ruthenium complexes have big potential. Some evidences suggest that ruthenium compounds possess anticancer activities. We synthesized two recently published ruthenium(III complexes with bidentate O,N and tridentate O,O,N Schiff bases derived from 5-substituted salicylaldehyde and aminophenol or anilineare. These compounds showed affinity for binding to the DNA molecule, however, insufficient data are available regarding their possible toxic effects on biological systems.Methods: In the present study we evaluated genotoxic, cytotoxic, and cytostatic effects of Na[RuCl2(L12] and Na[Ru(L22], using the Allium cepa assay.Results: Different toxic effects were observed depending on the substance, tested concentration, and endpoint measured. In general, the tested compounds significantly lowered the root growth and mitotic index values as compared to the control group. Additionally, a wide range of abnormal mitotic stages, both clastogenic and non-clastogenic were observed in the treated cells. Na[RuCl2(L12] significantly increased the frequency of sticky metaphases, chromosome bridges, micronuclei, impaired chromosome segregation, as well as number of apoptotic and necrotic cells over the controls. In contrast, Na[Ru(L22] did not show significant evidence of genotoxicity with regard to chromosome aberrations and micronuclei, however, significant differences were detected in the number of apoptotic and necrotic cells when the highest concentration was applied.Conclusions: In this study we demonstrated antiproliferative effects of Na[RuCl2(L12] and Na[Ru(L22]. At clinical level, these results could be interesting for further studies on anticancer potential of the ruthenium(III complexes using animal models.

  8. Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties.

    Science.gov (United States)

    Troeira Henriques, Sónia; Lawrence, Nicole; Chaousis, Stephanie; Ravipati, Anjaneya S; Cheneval, Olivier; Benfield, Aurélie H; Elliott, Alysha G; Kavanagh, Angela Maria; Cooper, Matthew A; Chan, Lai Yue; Huang, Yen-Hua; Craik, David J

    2017-09-15

    Gomesin, a disulfide-rich antimicrobial peptide produced by the Brazilian spider Acanthoscurria gomesiana, has been shown to be potent against Gram-negative bacteria and to possess selective anticancer properties against melanoma cells. In a recent study, a backbone cyclized analogue of gomesin was shown to be as active but more stable than its native form. In the current study, we were interested in improving the antimicrobial properties of the cyclic gomesin, understanding its selectivity toward melanoma cells and elucidating its antimicrobial and anticancer mode of action. Rationally designed analogues of cyclic gomesin were examined for their antimicrobial potency, selectivity toward cancer cells, membrane-binding affinity, and ability to disrupt cell and model membranes. We improved the activity of cyclic gomesin by ∼10-fold against tested Gram-negative and Gram-positive bacteria without increasing toxicity to human red blood cells. In addition, we showed that gomesin and its analogues are more toxic toward melanoma and leukemia cells than toward red blood cells and act by selectively targeting and disrupting cancer cell membranes. Preference toward some cancer types is likely dependent on their different cell membrane properties. Our findings highlight the potential of peptides as antimicrobial and anticancer leads and the importance of selectively targeting cancer cell membranes for drug development.

  9. Exploring the influence of culture conditions on kefir's anticancer properties.

    Science.gov (United States)

    Hatmal, Ma'mon M; Nuirat, Abeer; Zihlif, Malek A; Taha, Mutasem O

    2018-05-01

    Cancer is a major health problem in many parts of the world. Conventional anticancer treatments are painful, expensive, and unsafe. Therefore, demand is increasing for cancer treatments preferentially in the form of functional foods or nutritional supplements. Kefir, a traditional fermented milk dairy product, has significant antimutagenic and antitumor properties. This research addresses the hypothesis that kefir's anticancer properties are affected by fermentation conditions. Initially, kefir extracts prepared under standard conditions were screened against 7 cancer cell lines using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Colon cancer and chronic myelogenous leukemia cells were found to be most susceptible to kefir extracts. Subsequently, a factorial design was implemented to assess the effects of 3 fermentation times (24, 48, and 72 h), 3 kefir-to-milk ratios (2, 5, and 10% wt/vol), and 3 fermentation temperatures (4, 25, and 40°C) on kefir's anticancer properties. Remarkably, exploration of the fermentation conditions allowed the anticancer properties of kefir to be enhanced by 5- to 8-fold against susceptible cell lines. Overall, these results demonstrate the possibility of optimizing the anticancer properties of kefir as a functional food in cancer therapy. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-09-01

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

  11. Recent discoveries of anticancer flavonoids.

    Science.gov (United States)

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Plescia, Fabiana; Daidone, Giuseppe

    2017-12-15

    In this review we report the recent advances in anticancer activity of the family of natural occurring flavonoids, covering the time span of the last five years. The bibliographic data will be grouped, on the basis of biological information, in two great categories: reports in which the extract plants bioactivity is reported and the identification of each flavonoid is present or not, and reports in which the anticancer activity is attributable to purified and identified flavonoids from plants. Wherever possible, the targets and mechanisms of action as well as the structure-activity relationships of the molecules will be reported. Also, in the review it was thoroughly investigated the recent discovery on flavonoids containing the 2-phenyl-4H-chromen-4-one system even if some examples of unusual flavonoids, bearing a non-aromatic B-ring or other ring condensed to the base structure are reported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Application of radioimmunoassay for virus and anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Toyoshima, S. (Keio Univ., Tokyo (Japan). School of Medicine)

    1980-05-01

    Recent progress in RIA for virus and anticancer drugs was described. DNA and RNA virus and antivirus antibody which could be detected by RIA were mentioned, and then causes of arteriosclerosis, Paget's disease, multiple sclerosis, and diabetus mellitus were analysed virologically. Diagnostic significance of RIA was also described. Application of RIA to the measurement of interferon and carcinogenic virus at substantial level and recent information of viral hepatitis obtained by RIA were stated. Finally, application of RIA to the measurement of anticancer drugs acting on protective mechanism of the living body and measurement range by RIA were stated.

  13. Synthesis, characterization, antimicrobial and anticancer studies of new steroidal pyrazolines

    Directory of Open Access Journals (Sweden)

    Shamsuzzaman

    2016-01-01

    Full Text Available A convenient synthesis of 2′-(2″,4″-dinitrophenyl-5α-cholestano [5,7-c d] pyrazolines 4–6 from cholest-5-en-7-one 1–3 was performed and structural assignment of the products was confirmed on the basis of IR, 1H NMR, 13C NMR, MS and analytical data. The synthesized compounds were screened for in vitro antimicrobial activity against different strains during which compound 6 showed potent antimicrobial behaviour against Corynebacterium xerosis and Staphylococcus epidermidis. The synthesized compounds were also screened for in vitro anticancer activity against human cancer cell lines during which compound 5 exhibited significant anticancer activity.

  14. Application of radioimmunoassay for virus and anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Toyoshima, S [Keio Univ., Tokyo (Japan). School of Medicine

    1980-05-01

    Recent progress in RIA for virus and anticancer drugs was described. DNA and RNA virus and antivirus antibody which could be detected by RIA were mentioned, and then causes of arteriosclerosis, Paget's disease, multiple sclerosis, and diabetus mellitus were analysed virologically. Diagnostic significance of RIA was also described. Application of RIA to the measurement of interferon and carcinogenic virus at substantial level and recent information of viral hepatitis obtained by RIA were stated. Finally, application of RIA to the measurement of anticancer drugs acting on protective mechanism of the living body and measurement range by RIA were stated.

  15. Male homosexuality and spirit possession in Brazil.

    Science.gov (United States)

    Fry, P

    1985-01-01

    This paper examines the relationship between male homosexuality and the Afro-Brazilian possession cults in Belém do Parà. After a discussion of the literature follows a description of the cults' beliefs, rites and social organization. Male sex roles are then discussed and the two categories, bicha and man, analyzed. It is noted that there is no term which is equivalent to the western category of "homosexual" in this taxonomic system. After putting forward folk explanations for the presence of many bichas in the cults, an analysis is put forward of the social rewards available to bichas within these cults, and the structural relationship between homosexuality and these regions in terms of their congruent marginality vis-à-vis "normal society."

  16. Heterocyclic Scaffolds: Centrality in Anticancer Drug Development.

    Science.gov (United States)

    Ali, Imran; Lone, Mohammad Nadeem; Al-Othman, Zeid A; Al-Warthan, Abdulrahman; Sanagi, Mohd Marsin

    2015-01-01

    Cancer has been cursed for human beings for long time. Millions people lost their lives due to cancer. Despite of the several anticancer drugs available, cancer cannot be cured; especially at the late stages without showing any side effect. Heterocyclic compounds exhibit exciting medicinal properties including anticancer. Some market selling heterocyclic anticancer drugs include 5-flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some natural products such as vinblastine and vincristine are also used as anticancer drugs. Overall, heterocyclic moeities have always been core parts in the expansion of anticancer drugs. This article describes the importance of heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts have been made to discuss both naturally occurring and synthetic heterocyclic compounds as anticancer agents. In addition, some market selling anticancer heterocyclic compounds have been described. Moreover, the efforts have been made to discuss the mechanisms of actions and recent advances in heterocyclic compounds as anticancer agents. The current challenges and future prospectives of heterocyclic compounds have also been discussed. Finally, the suggestions for syntheses of effective, selective, fast and human friendly anticancer agents are discussed into the different sections.

  17. PEGylated Silk Nanoparticles for Anticancer Drug Delivery.

    Science.gov (United States)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew J; Seib, F Philipp

    2015-11-09

    Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of "stealth" design principals is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential -56 ± 5.6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines to human breast cancer cells. In conclusion, these results, taken together with prior silk nanoparticle data, support a viable future for silk-based nanomedicines.

  18. The anticancer effect of Ocimum tenuiflorum leaves

    Directory of Open Access Journals (Sweden)

    Lam, S.N.

    2017-11-01

    Full Text Available Breast cancer is the leading cause of cancer deaths among females in Malaysia. Ocimum tenuiflorum L., (O. tenuiflorum commonly known as ruku in Malaysia, is usually cultivated as a garden ornamental plant because of its small purplish and some yellowish flower. The specific objective of this research is to investigate the anticancer of O. tenuiflorum against human breast cancer cell lines (MCF-7 and MDA-MB-231 and human fibroblast cell line (HS-27. In addition, another objective is to determine the mineral and heavy metal determination of O. tenuiflorum. O. tenuiflorum exhibited anticancer activity against MCF-7 (a hormone-dependent breast cancer cell line. The viability of MCF-7 cells decreased significantly after treatment with various concentrations of methanolic plant extracts (25 and 100 μg/mL, as shown via 3-(4,5-dimethylthiazol-2-yl2,5-diphenyltetrazolium bromide (MTT assay. The crude extracts show the lower IC50 (less than 100 μg/mL value against the cancer cell lines and show no effect on HS-27. The high content of calcium in the leaves of O. tenuiflorum may play a role in decreasing the risk of certain cancer. The concentrations of heavy metals (Pb and As detected in O. tenuiflorum are safe for consumption.

  19. Predicative possession in Medieval Slavic Bible translations Predicative Possession in Early Biblical Slavic

    Directory of Open Access Journals (Sweden)

    Julia McAnallen

    2011-08-01

    Full Text Available Late Proto-Slavic (LPS had an inventory of three constructions for expressing predicative possession. Using the earliest Slavic Bible translations from Old Church Slavic (OCS, and to a lesser degree Old Czech, a number of conclusions can be drawn about the status of predicative possession for LPS. The verb iměti ‘have’ was the most frequent and least syntactically and semantically restricted predicative possessive construction (PPC. Existential PPCs with a dative possessor appear primarily with kinship relations, abstract possessums, and in a number of other fixed construction types; existential PPCs with the possessor in an u + genitive prepositional phrase primarily appear with concrete and countable possessums. Both existential PPCs call for an animate, most often pronominal, possessor. The u + genitive was the rarest type of PPC in LPS, though it had undoubtedly grammaticalized as a PPC.

  20. 50 CFR 20.38 - Possession of live birds.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Possession of live birds. 20.38 Section 20... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Possession § 20.38 Possession of live birds. Every migratory game bird wounded by hunting and reduced to possession by the hunter shall be immediately killed...

  1. Traumatic Experience and Somatoform Dissociation Among Spirit Possession Practitioners in the Dominican Republic.

    Science.gov (United States)

    Schaffler, Yvonne; Cardeña, Etzel; Reijman, Sophie; Haluza, Daniela

    2016-03-01

    Recent studies in African contexts have revealed a strong association between spirit possession and severe trauma, with inclusion into a possession cult serving at times a therapeutic function. Research on spirit possession in the Dominican Republic has so far not included quantitative studies of trauma and dissociation. This study evaluated demographic variables, somatoform dissociative symptoms, and potentially traumatizing events in the Dominican Republic with a group of Vodou practitioners that either do or do not experience spirit possession. Inter-group comparisons revealed that in contrast to non-possessed participants (n = 38), those experiencing spirit possession (n = 47) reported greater somatoform dissociation, more problems with sleep, and previous exposure to mortal danger such as assaults, accidents, or diseases. The two groups did not differ significantly in other types of trauma. The best predictor variable for group classification was somatoform dissociation, although those items could also reflect the experience of followers during a possession episode. A factor analysis across variables resulted in three factors: having to take responsibility early on in life and taking on a professional spiritual role; traumatic events and pain; and distress/dissociation. In comparison with the non-possessed individuals, the possessed ones did not seem to overall have a remarkably more severe story of trauma and seemed to derive economic gains from possession practice.

  2. Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers.

    Science.gov (United States)

    Li, Guang; Yu, Kai; Li, Fushuang; Xu, Kangping; Li, Jing; He, Shujin; Cao, Shousong; Tan, Guishan

    2014-04-28

    Hericium is a genus of mushrooms (fungus) in the Hericiaceae family. Hericium erinaceus (HE) has been used for the treatment of digestive diseases for over 2000 years in China. HE possesses many beneficial functions such as anticancer, antiulcer, antiinflammation and antimicrobial effects, immunomodulation and other activities. The aim of the studies was to evaluate the anticancer efficacy of two extracts (HTJ5 and HTJ5A) from the culture broth of HE against three gastrointestinal cancers such as liver, colorectal and gastric cancers in both of in vitro of cancer cell lines and in vivo of tumor xenografts and discover the active compounds. Two HE extracts (HTJ5 and HTJ5A) were used for the studies. For the study of chemical constituents, the HTJ5 and HTJ5A were separated using a combination of macroporous resin with silica gel, HW-40 and LH-20 chromatography then purified by semipreparative high-performance liquid chromatography (HPLC) and determined by nuclear magnetic resonance (NMR) spectra. For the in vitro cytotoxicity studies, HepG2 and Huh-7 liver, HT-29 colon, and NCI-87 gastric cancer cell lines were used and MTT assay was performed to determine the in vitro cytotoxicity. For in vivo antitumor efficacy and toxicity studies, tumor xenograft models of SCID mice bearing liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 subcutaneously were used and the mice were treated with the vehicle control, HTJ5 and HTJ5A orally (500 and 1000 mg/kg/day) and compared to 5-fluorouraci (5-FU) at the maximum tolerated dose (MTD, 25-30 mg/kg/day) intraperitoneally daily for 5 days when the tumors reached about 180-200 mg (mm(3)). Tumor volumes and body weight were measured daily during the first 10 days and 2-3 times a week thereafter to assess the tumor growth inhibition, tumor doubling time, partial and complete tumor response and toxicity. Twenty-two compounds were obtained from the fractions of HTJ5/HTJ5A including seven cycli dipeptides, five

  3. Emotional regulation, attachment to possessions and hoarding symptoms.

    Science.gov (United States)

    Phung, Philip J; Moulding, Richard; Taylor, Jasmine K; Nedeljkovic, Maja

    2015-10-01

    This study aimed to test which particular facets of emotion regulation (ER) are most linked to symptoms of hoarding disorder, and whether beliefs about emotional attachment to possessions (EA) mediate this relationship. A non-clinical sample of 150 participants (108 females) completed questionnaires of emotional tolerance (distress tolerance, anxiety sensitivity, negative urgency - impulsivity when experiencing negative emotions), depressed mood, hoarding, and beliefs about emotional attachment to possessions. While all emotional tolerance measures related to hoarding, when considered together and controlling for depression and age, anxiety sensitivity and urgency were the significant predictors. Anxiety sensitivity was fully mediated, and urgency partially mediated, via beliefs regarding emotional attachment to possessions. These findings provide further support for (1) the importance of anxiety sensitivity and negative urgency for hoarding symptoms, and (2) the view that individuals with HD symptoms may rely on items for emotion regulation, leading to stronger beliefs that items are integral to emotional wellbeing. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  4. Structure-directing star-shaped block copolymers: supramolecular vesicles for the delivery of anticancer drugs.

    Science.gov (United States)

    Yang, Chuan; Liu, Shao Qiong; Venkataraman, Shrinivas; Gao, Shu Jun; Ke, Xiyu; Chia, Xin Tian; Hedrick, James L; Yang, Yi Yan

    2015-06-28

    Amphiphilic polycarbonate/PEG copolymer with a star-like architecture was designed to facilitate a unique supramolecular transformation of micelles to vesicles in aqueous solution for the efficient delivery of anticancer drugs. The star-shaped amphipilic block copolymer was synthesized by initiating the ring-opening polymerization of trimethylene carbonate (TMC) from methyl cholate through a combination of metal-free organo-catalytic living ring-opening polymerization and post-polymerization chain-end derivatization strategies. Subsequently, the self-assembly of the star-like polymer in aqueous solution into nanosized vesicles for anti-cancer drug delivery was studied. DOX was physically encapsulated into vesicles by dialysis and drug loading level was significant (22.5% in weight) for DOX. Importantly, DOX-loaded nanoparticles self-assembled from the star-like copolymer exhibited greater kinetic stability and higher DOX loading capacity than micelles prepared from cholesterol-initiated diblock analogue. The advantageous disparity is believed to be due to the transformation of micelles (diblock copolymer) to vesicles (star-like block copolymer) that possess greater core space for drug loading as well as the ability of such supramolecular structures to encapsulate DOX. DOX-loaded vesicles effectively inhibited the proliferation of 4T1, MDA-MB-231 and BT-474 cells, with IC50 values of 10, 1.5 and 1.0mg/L, respectively. DOX-loaded vesicles injected into 4T1 tumor-bearing mice exhibited enhanced accumulation in tumor tissue due to the enhanced permeation and retention (EPR) effect. Importantly, DOX-loaded vesicles demonstrated greater tumor growth inhibition than free DOX without causing significant body weight loss or cardiotoxicity. The unique ability of the star-like copolymer emanating from the methyl cholate core provided the requisite modification in the block copolymer interfacial curvature to generate vesicles of high loading capacity for DOX with significant

  5. [The Necessity and the Current Status of Safe Handling of Anticancer Drugs].

    Science.gov (United States)

    Kanda, Kiyoko

    2017-07-01

    Number of people who handle anticancer drugs in their profession is increasing. Anticancer drugs, which are hazardous drugs(HD), exert cytocidal effects on cancer cells, but many have also been shown to have mutagenicity, teratogenicity and carcinogenicity; therefore, safe handling of anticancer drugs is necessary. In July 2015, the first Japanese guidelines for exposure control measures, namely, the "Joint Guidelines for Safe Handling of Cancer Chemotherapy Drugs", were published jointly by 3 societies. Our guideline is the creation of the Japanese Society of Cancer Nursing(JSCN), Japanese Society of Medical Oncology(JSMO)and Japanese Society of Pharmaceutical Oncology(JASPO)and has a historical significance. This paper states the necessity of safe handling of anticancer drugs, Japan's recent movement of safe handling, the introduction of joint guidelines of safe handling of anticancer drugs, and new movement of safe handling of USP chapter 800 in the United States.

  6. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  7. 22 CFR 72.14 - Nominal possession; property not normally taken into physical possession.

    Science.gov (United States)

    2010-04-01

    ... possession. (a) When a consular officer take articles of a decedent's personal property from a foreign... Department discharging the consular officer of any responsibility for the articles transferred. (b) A... effects; (2) Motor vehicles, airplanes or watercraft; (3) Toiletries, such as toothpaste or razors; (4...

  8. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian-Zheng, E-mail: wppzheng@126.com [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Zhu, Yu-Xia [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang [Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Meng, Yue-Zhong [State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou 510275 (China)

    2016-05-01

    In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose–lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. - Highlights: • Chitosan/collagen/alginate (CCA) scaffolds were fabricated by spray-spinning. • MCF-7 cells presented a multi-cellular tumor spheroid model (MCTS) in CCA scaffold. • MCTS in CCA possessed a more conservative phenotype of tumor than monolayer cells. • Anticancer drug screening in MCTS-CCA system is superior to 2D culture system.

  9. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening

    International Nuclear Information System (INIS)

    Wang, Jian-Zheng; Zhu, Yu-Xia; Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang; Meng, Yue-Zhong

    2016-01-01

    In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose–lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. - Highlights: • Chitosan/collagen/alginate (CCA) scaffolds were fabricated by spray-spinning. • MCF-7 cells presented a multi-cellular tumor spheroid model (MCTS) in CCA scaffold. • MCTS in CCA possessed a more conservative phenotype of tumor than monolayer cells. • Anticancer drug screening in MCTS-CCA system is superior to 2D culture system.

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

    Science.gov (United States)

    Rahman, Md Azizur; Sahabjada; Akhtar, Juber

    2017-07-01

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

  11. Ganoderma: insights into anticancer effects.

    Science.gov (United States)

    Kladar, Nebojša V; Gavarić, Neda S; Božin, Biljana N

    2016-09-01

    The genus Ganoderma includes about 80 species growing on cut or rotten trees. The most commonly used species is Ganoderma ludicum. Biomolecules responsible for the health benefits of Ganoderma are polysaccharides with an immunostimulative effect and triterpenes with a cytotoxic action. For more than 2000 years, it has been used traditionally in the treatment of various pathological conditions and recently, its immunoregulatory, antiviral, antibacterial, antioxidant, hepatoprotective, and anticancer potential has been confirmed. A wide range of Ganoderma extracts and preparations arrest the cell cycle in different phases and consequently inhibit the growth of various types of cancer cells. Extracts containing polysaccharides stimulate immunological reactions through the production of various cytokines and mobilization of immune system cells. In-vivo studies have confirmed the anticancer potential and the antimetastatic effects of compounds originating from Ganoderma. There is also evidence for the chemopreventive action of Ganoderma extracts in bladder, prostate, liver, and breast cancer. The results of clinical studies suggest the combined use of G. lucidum with conventional chemotherapy/radiotherapy, but the methodology and the results of these studies are being questioned. Therefore, a constant need for new clinical trials exists.

  12. Possession Zone as a Performance Indicator in Football. The Game of the Best Teams

    Directory of Open Access Journals (Sweden)

    Claudio A. Casal

    2017-07-01

    Full Text Available Possession time in football has been widely discussed in research but few studies have analyzed the importance of the field area in which possession occurs. The objective of this study was to identify the existence of significant differences in the field zone of ball possession between successful and unsuccessful teams and to acknowledge if the match status modulates the possession model. To this end, 2,284 attacks were analyzed corresponding to the matches in the final phase of the UEFA Euro 2016 France, recording possession time and field zone in which possession occurred. Video recordings of matches were analyzed and coded post-event using notational analysis. We have found that successful offensive game patterns are different from unsuccessful ones. Specifically, field zone in which major possession occurs changes significantly between successful and unsuccessful teams (x2 = 15.72, p < 0.05 and through Welch’s T significant differences were detected in possession time between successful and unsuccessful teams (H = 24.289, p < 0.001. The former are characterized by longer possession times, preferably in the middle offensive zone, on the other hand, unsuccessful teams have shorter possession times and preferably on the middle defensive zone. Logistic regression also allowed us to identify that greater possession in the middle offensive zone is a good indicator of success in the offensive game, allowing us to predict a greater chance of victory in the match. Specifically, every time the teams achieve possession in the middle offensive zone, the chance of winning the match will increase 1.72 times and, the probability of winning the match making longer possessions in the middle offensive zone is 44.25%. Applying the Kruskal–Wallis test we have also been able to verify how match status modulates the teams possession time, specifically, when teams are winning they have longer possessions x2 = 92.628, p = 0.011. Results obtained are expected to

  13. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  14. Optimization of personalized therapies for anticancer treatment.

    Science.gov (United States)

    Vazquez, Alexei

    2013-04-12

    As today, there are hundreds of targeted therapies for the treatment of cancer, many of which have companion biomarkers that are in use to inform treatment decisions. If we would consider this whole arsenal of targeted therapies as a treatment option for every patient, very soon we will reach a scenario where each patient is positive for several markers suggesting their treatment with several targeted therapies. Given the documented side effects of anticancer drugs, it is clear that such a strategy is unfeasible. Here, we propose a strategy that optimizes the design of combinatorial therapies to achieve the best response rates with the minimal toxicity. In this methodology markers are assigned to drugs such that we achieve a high overall response rate while using personalized combinations of minimal size. We tested this methodology in an in silico cancer patient cohort, constructed from in vitro data for 714 cell lines and 138 drugs reported by the Sanger Institute. Our analysis indicates that, even in the context of personalized medicine, combinations of three or more drugs are required to achieve high response rates. Furthermore, patient-to-patient variations in pharmacokinetics have a significant impact in the overall response rate. A 10 fold increase in the pharmacokinetics variations resulted in a significant drop the overall response rate. The design of optimal combinatorial therapy for anticancer treatment requires a transition from the one-drug/one-biomarker approach to global strategies that simultaneously assign makers to a catalog of drugs. The methodology reported here provides a framework to achieve this transition.

  15. Anticancer Properties of Distinct Antimalarial Drug Classes

    Science.gov (United States)

    Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

    2013-01-01

    We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

  16. Dual function of tributyrin emulsion: solubilization and enhancement of anticancer effect of celecoxib.

    Science.gov (United States)

    Kang, Sung Nam; Hong, Soon-Seok; Lee, Mi-Kyung; Lim, Soo-Jeong

    2012-05-30

    Tributyrin, a triglyceride analogue of butyrate, can act as a prodrug of an anticancer agent butyrate after being cleaved by intracellular enzymes. We recently demonstrated that the emulsion containing tributyrin as an inner oil phase possesses a potent anticancer activity. Herein we sought to develop tributyrin emulsion as a carrier of celecoxib, a poorly-water soluble drug with anticancer activity. Combined treatment of human HCT116 colon cancer cells with free celecoxib plus tributyrin emulsion inhibited the cellular proliferation more effectively than that of each drug alone, suggesting the possibility of tributyrin emulsion as a potential celecoxib carrier. The mean droplet size of emulsions tended to increase as the tributyrin content in emulsion increases and the concentration of celecoxib loaded in emulsions was affected by tributyrin content and the initial amount of celecoxib, but not by the total amount of surfactant mixture. The concentration of celecoxib required to inhibit the growth of HCT116 and B16-F10 cancer cells by 50% was 2.6- and 3.1-fold lowered by loading celecoxib in tributyrin emulsions, compared with free celecoxib. These data suggest that the anticancer activity of celecoxib was enhanced by loading in tributyrin emulsions, probably due to the solubilization capacity and anticancer activity of tributyrin emulsion. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. The anti-cancer components of Ganoderma lucidum possesses cardiovascular protective effect by regulating circular RNA expression

    Science.gov (United States)

    Tan, Weijiang; Li, Xiangmin; Jiao, Chunwei; Huang, Ren; Yang, Burton B.

    2016-01-01

    To examine the role of oral Ganoderma spore oil in cardiovascular disease, we used transverse aortic constriction (TAC) in mice to model pressure overload-induced cardiomyopathy. Our preliminary results demonstrated a potential cardioprotective role for spore oil extracted from Ganoderma. We found that Ganoderma treatment normalized ejection fraction and corrected the fractional shortening generated by TAC. We also found evidence of reduced left ventricular hypertrophy as assessed by left ventricular end diastolic diameter. Analysis of total RNA expression using cardiac tissue samples from these mice corroborated our findings. We found reduced expression of genes associated with heart failure, including a novel circular RNA circ-Foxo3. Thus our data provides evidence for Ganoderma lucidum as a potential cardioprotective agent, warranting further preclinical exploration. PMID:27713910

  18. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  19. Possession States: Approaches to Clinical Evaluation and Classification

    Directory of Open Access Journals (Sweden)

    S. McCormick

    1992-01-01

    Full Text Available The fields of anthropology and sociology have produced a large quantity of literature on possession states, physicians however rarely report on such phenomena. As a result clinical description of possession states has suffered, even though these states may be more common and less deviant than supposed. Both ICD-10 and DSM-IV may include specific criteria for possession disorders. The authors briefly review Western notions about possession and kindred states and present guidelines for evaluation and classification.

  20. [Anticancer propaganda: myth or reality?].

    Science.gov (United States)

    Demin, E V; Merabishvili, V M

    2014-01-01

    The authors raise a very important problem of anticancer propaganda aimed at the early detection of cancer to be solved nowadays by means of screening and constructive interaction between oncologists and the public. To increase the level of knowledge of the population in this area it is necessary to expand the range of its adequate awareness of tumor diseases. Only joint efforts can limit the destructive effect of cancer on people's minds, so that every person would be responsible for his own health, clearly understanding the advantages of early visit to a doctor. This once again highlights the need of educational work with the public, motivational nature of which allows strengthening the value of screening in the whole complex of measures to fight cancer.

  1. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic drugs

  2. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil; Kaur, Mandeep; Esau, Luke E.

    2014-01-01

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic drugs

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

    Science.gov (United States)

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

    2015-01-01

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

  4. STRUCTURE MODIFICATION OF ANDROGRAPHOLIDE TO IMPROVE ITS POTENCY AS ANTICANCER

    Directory of Open Access Journals (Sweden)

    Hadi Poerwono

    2010-06-01

    Full Text Available Andrographolide, a diterpenoid lactone isolated from the herb of Andrographis paniculata and known to possess antitumor activity in breast cancer models was subjected to semisynthesis leading to the preparation of a number of derivatives. After protection of the two hydroxyl groups present at C-3 and C-19 to give 3,19-isopropylidene and 3,19-benzylidene andrographolides, the remaining hydroxyl group at C-14 of andrographolide was treated with acid anhydride or acid chloride under base condition. Unfortunately, the reactions gave only 14-dehydroandrographolide as well as unidentified diacyl compounds in replace of the target molecule 14-O-acyl andrographolide. An alternative procedure using neat acetic anhydride under reflux gave the acetyl derivatives. The resulted compounds exhibited cytotoxic activity against MCF-7 breast cancer cells with better growth inhibition than the parent compound andrographolide.   Keywords: andrographolide, acylation, anticancer, cytotoxic, breast cancer cells.

  5. Marine Fungi: A Source of Potential Anticancer Compounds

    Directory of Open Access Journals (Sweden)

    Sunil K. Deshmukh

    2018-01-01

    Full Text Available Metabolites from marine fungi have hogged the limelight in drug discovery because of their promise as therapeutic agents. A number of metabolites related to marine fungi have been discovered from various sources which are known to possess a range of activities as antibacterial, antiviral and anticancer agents. Although, over a thousand marine fungi based metabolites have already been reported, none of them have reached the market yet which could partly be related to non-comprehensive screening approaches and lack of sustained lead optimization. The origin of these marine fungal metabolites is varied as their habitats have been reported from various sources such as sponge, algae, mangrove derived fungi, and fungi from bottom sediments. The importance of these natural compounds is based on their cytotoxicity and related activities that emanate from the diversity in their chemical structures and functional groups present on them. This review covers the majority of anticancer compounds isolated from marine fungi during 2012–2016 against specific cancer cell lines.

  6. Unique characteristics of regulatory approval and pivotal studies of orphan anticancer drugs in Japan.

    Science.gov (United States)

    Nakayama, Hiroki; Tsukamoto, Katsura

    2018-04-17

    The approval of orphan anticancer drugs has increased, with the number exceeding that of non-orphan drugs in Japan in recent years. Although orphan anticancer drugs may have unique characteristics due to their rarity, these have not been fully characterized. We investigated anticancer drugs approved in Japan between April 2004 and November 2017 to reveal the characteristics of regulatory approval and pivotal studies on orphan anticancer drugs compared to non-orphan drugs. The median regulatory review time and number of patients in pivotal studies on orphan anticancer drugs (281.0 days [interquartile range, 263.3-336.0]; 222.5 patients [66.0-454.3]) were significantly lower than those on non-orphan drugs (353.0 days [277.0-535.5]; 521.0 patients [303.5-814.5], respectively) (P < 0.001). Phase II, non-randomized and non-controlled designs were more frequently used in pivotal studies on orphan anticancer drugs (45.9%, 41.9% and 43.2%) than non-orphan drugs (17.2%, 14.1% and 14.1%, respectively). Response rate was more commonly used as a primary endpoint in pivotal studies on orphan anticancer drugs (48.6%) than non-orphan drugs (17.2%). Indications limited by molecular features, second or later treatment line, and accelerated approval in the United States were associated with the use of response rate in orphan anticancer drug studies. In conclusion, we demonstrated that orphan anticancer drugs in Japan have unique characteristics compared to non-orphan drugs: shorter regulatory review and pivotal studies frequently using phase II, non-randomized, or non-controlled designs and response rate as a primary endpoint, with fewer patients.

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

    Science.gov (United States)

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

    2013-11-25

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

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

    Directory of Open Access Journals (Sweden)

    Navneet Kumar Yadav

    2017-01-01

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

  9. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    Norman eWoller

    2014-07-01

    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  10. Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies.

    Science.gov (United States)

    Panebianco, Concetta; Andriulli, Angelo; Pazienza, Valerio

    2018-05-22

    Cancer is a major health burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. There is a growing evidence that gut bacteria can affect the response to chemo- and immunotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. Here, we review the existing knowledge concerning the role of the microbiota in mediating chemo- and immunotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments.

  11. Marine Microalgae with Anti-Cancer Properties.

    Science.gov (United States)

    Martínez Andrade, Kevin A; Lauritano, Chiara; Romano, Giovanna; Ianora, Adrianna

    2018-05-15

    Cancer is the leading cause of death globally and finding new therapeutic agents for cancer treatment remains a major challenge in the pursuit for a cure. This paper presents an overview on microalgae with anti-cancer activities. Microalgae are eukaryotic unicellular plants that contribute up to 40% of global primary productivity. They are excellent sources of pigments, lipids, carotenoids, omega-3 fatty acids, polysaccharides, vitamins and other fine chemicals, and there is an increasing demand for their use as nutraceuticals and food supplements. Some microalgae are also reported as having anti-cancer activity. In this review, we report the microalgal species that have shown anti-cancer properties, the cancer cell lines affected by algae and the concentrations of compounds/extracts tested to induce arrest of cell growth. We also report the mediums used for growing microalgae that showed anti-cancer activity and compare the bioactivity of these microalgae with marine anticancer drugs already on the market and in phase III clinical trials. Finally, we discuss why some microalgae can be promising sources of anti-cancer compounds for future development.

  12. Zirconium Phosphate Nanoplatelet Potential for Anticancer Drug Delivery Applications.

    Science.gov (United States)

    González, Millie L; Ortiz, Mayra; Hernández, Carmen; Cabán, Jennifer; Rodríguez, Axel; Colón, Jorge L; Báez, Adriana

    2016-01-01

    Zirconium phosphate (ZrP) nanoplatelets can intercalate anticancer agents via an ion exchange reaction creating an inorganic delivery system with potential for cancer treatment. ZrP delivery of anticancer agents inside tumor cells was explored in vitro. Internalization and cytotoxicity of ZrP nanoplatelets were studied in MCF-7 and MCF-10A cells. DOX-loaded ZrP nanoplatelets (DOX@ZrP) uptake was assessed by confocal (CLSM) and transmission electron microscopy (TEM). Cytotoxicity to MCF-7 and MCF-10A cells was determined by the MTT assay. Reactive Oxy- gen Species (ROS) production was analyzed by fluorometric assay, and cell cycle alterations and induction of apoptosis were analyzed by flow cytometry. ZrP nanoplatelets were localized in the endosomes of MCF-7 cells. DOX and ZrP nanoplatelets were co-internalized into MCF-7 cells as detected by CLSM. While ZrP showed limited toxicity to MCF-7 cells, DOX@ZrP was cytotoxic at an IC₅₀ similar to that of free DOX. Meanwhile, DOX lC₅₀ was significantly lower than the equivalent concentration of DOX@ZrP in MCF-10A cells. ZrP did not induce apoptosis in both cell lines. DOX and DOX@ZrP induced significant oxidative stress in both cell models. Results suggest that ZrP nanoplatelets are promising as carriers of anticancer agents into cancer cells.

  13. Pathological spirit possession as a cultural interpretation of trauma-related symptoms.

    Science.gov (United States)

    Hecker, Tobias; Barnewitz, Eva; Stenmark, Hakon; Iversen, Valentina

    2016-07-01

    Spirit possession is a phenomenon frequently occurring in war-torn countries. It has been shown to be an idiom of distress entailing dissociative symptoms. However, its association with trauma exposure and trauma-related disorders remains unclear. This study aimed to explore subjective disease models and the relationship between pathological spirit possession and trauma-related disorders in the Eastern Democratic Republic of the Congo. Seventy-three (formerly) possessed persons (74% female, mean age = 34 years), referred by traditional and spiritual healers, were interviewed about their experiences of pathological spirit possession, trauma exposure, posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, shame and guilt, psychotic symptoms, somatic complaints, and the impairment of psychosocial functioning. The most common disease model for pathological spirit possession was another person having sent the spirit, mostly a family member or a neighbor, out of jealousy or conflict over resources. Significant correlations were found between spirit possession over lifetime and PTSD symptom severity, feelings of shame and guilt, depressive symptoms, somatic complaints, and psychotic symptoms. Spirit possession during the preceding 4 weeks was associated with PTSD symptom severity, impairment of psychosocial functioning, and psychotic symptom severity. The results of this study indicate that pathological spirit possession is a broad explanatory framework for various subjectively unexplainable mental and physical health problems, including but not limited to trauma-related disorders. Understanding pathological spirit possession as a subjective disease model for various mental and physical health problems may help researchers and clinicians to develop culturally sensitive treatment approaches for affected individuals. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. Possession experiences in dissociative identity disorder: a preliminary study.

    Science.gov (United States)

    Ross, Colin A

    2011-01-01

    Dissociative trance disorder, which includes possession experiences, was introduced as a provisional diagnosis requiring further study in the Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Consideration is now being given to including possession experiences within dissociative identity disorder (DID) in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.), which is due to be published in 2013. In order to provide empirical data relevant to the relationship between DID and possession states, I analyzed data on the prevalence of trance, possession states, sleepwalking, and paranormal experiences in 3 large samples: patients with DID from North America; psychiatric outpatients from Shanghai, China; and a general population sample from Winnipeg, Canada. Trance, sleepwalking, paranormal, and possession experiences were much more common in the DID patients than in the 2 comparison samples. The study is preliminary and exploratory in nature because the samples were not matched in any way.

  15. Cinnamon in Anticancer Armamentarium: A Molecular Approach

    Directory of Open Access Journals (Sweden)

    Anindita Dutta

    2018-01-01

    Full Text Available In recent years, natural bioactive components draw a major attention for their potent anticarcinogenic activity. Cinnamon, one of the traditional spices, most frequently used in almost every household of tropical countries has got enormous efficacy to combat cancer. Cinnamon as a whole and/or its active components exhibited significant antineoplastic activity in different types of cancer. This review has been carried out to elicit the molecular mechanisms of action of cinnamon and its components on oncogenic regulators and related pathways. Web sites of Google Scholar, Medline, and PubMed were searched for articles written in English and published in peer-reviewed journals from 2003 to 2017. The anticarcinogenic potential of cinnamon varies with the type of cancer and also depends on the administered active compound individually or in combination with some chemicals or even extract of cinnamon as a whole. Some of its active components exert chemosensitization of well-known anticancer drugs. These outstanding properties of this spice necessitate its incorporation in both pharmaceuticals and nutraceuticals to explore possibilities of formulation of novel drug from this spice for treatment and prevention strategy of cancer.

  16. Anticancer Activity of Sea Cucumber Triterpene Glycosides

    Directory of Open Access Journals (Sweden)

    Dmitry L. Aminin

    2015-03-01

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

  17. Fluorescence optical imaging in anticancer drug delivery.

    Science.gov (United States)

    Etrych, Tomáš; Lucas, Henrike; Janoušková, Olga; Chytil, Petr; Mueller, Thomas; Mäder, Karsten

    2016-03-28

    In the past several decades, nanosized drug delivery systems with various targeting functions and controlled drug release capabilities inside targeted tissues or cells have been intensively studied. Understanding their pharmacokinetic properties is crucial for the successful transition of this research into clinical practice. Among others, fluorescence imaging has become one of the most commonly used imaging tools in pre-clinical research. The development of increasing numbers of suitable fluorescent dyes excitable in the visible to near-infrared wavelengths of the spectrum has significantly expanded the applicability of fluorescence imaging. This paper focuses on the potential applications and limitations of non-invasive imaging techniques in the field of drug delivery, especially in anticancer therapy. Fluorescent imaging at both the cellular and systemic levels is discussed in detail. Additionally, we explore the possibility for simultaneous treatment and imaging using theranostics and combinations of different imaging techniques, e.g., fluorescence imaging with computed tomography. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening.

    Science.gov (United States)

    Wang, Jian-Zheng; Zhu, Yu-Xia; Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang; Meng, Yue-Zhong

    2016-05-01

    In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose-lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. A rapid in vitro screening system for the identification and evaluation of anticancer drugs

    International Nuclear Information System (INIS)

    Kao, J.W.; Collins, J.L.

    1989-01-01

    We report the development of an in vitro screening system that can be used to identify new anticancer drugs that are specifically cytotoxic for dividing cells. The screening system takes advantage of the potential of many cell lines, including tumor cells, to stop dividing when they are plated at high cell density. The cytotoxic effects of anticancer drugs on dividing (i.e., cells plated at low cell density) and nondividing cells (i.e., cells plated at high cell density) is measured by the incorporation of 51Cr. This in vitro system was evaluated by measuring the cytotoxic effects of the anticancer drugs cisplatin, thiotepa, doxorubicin, methotrexate, and vinblastine on the cell lines B/C-N, ME-180, and MCF-7. In this in vitro system the concentrations of the anticancer drugs that produced significant cytotoxicity on only dividing cells are similar to the concentrations that are used clinically. The fact that this in vitro system is rapid, simple, applicable to many cell types, and able to predict effective concentrations of anticancer drugs should make it useful for the screening of new anticancer drugs and for the design of preclinical studies

  20. Anticancer Principles from Medicinal Piper (胡椒 Hú Jiāo Plants

    Directory of Open Access Journals (Sweden)

    Yue-Hu Wang

    2014-01-01

    Full Text Available The ethnomedical uses of Piper (胡椒 Hú Jiāo plants as anticancer agents, in vitro cytotoxic activity of both extracts and compounds from Piper plants, and in vivo antitumor activity and mechanism of action of selected compounds are reviewed in the present paper. The genus Piper (Piperaceae contains approximately 2000 species, of which 10 species have been used in traditional medicines to treat cancer or cancer-like symptoms. Studies have shown that 35 extracts from 24 Piper species and 32 compounds from Piper plants possess cytotoxic activity. Amide alkaloids account for 53% of the major active principles. Among them, piplartine (piperlongumine shows the most promise, being toxic to dozens of cancer cell lines and having excellent in vivo activity. It is worthwhile to conduct further anticancer studies both in vitro and in vivo on Piper plants and their active principles.

  1. Anticancer drugs from marine flora: an overview.

    Science.gov (United States)

    Sithranga Boopathy, N; Kathiresan, K

    2010-01-01

    Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. The chemicals have displayed an array of pharmacological properties especially antioxidant, immunostimulatory, and antitumour activities. The phytochemicals possibly activate macrophages, induce apoptosis, and prevent oxidative damage of DNA, thereby controlling carcinogenesis. In spite of vast resources enriched with chemicals, the marine floras are largely unexplored for anticancer lead compounds. Hence, this paper reviews the works so far conducted on this aspect with a view to provide a baseline information for promoting the marine flora-based anticancer research in the present context of increasing cancer incidence, deprived of the cheaper, safer, and potent medicines to challenge the dreadful human disease.

  2. 20 CFR 404.1093 - Possession of the United States.

    Science.gov (United States)

    2010-04-01

    ... DISABILITY INSURANCE (1950- ) Employment, Wages, Self-Employment, and Self-Employment Income Self-Employment... figuring your net earnings from self-employment, the term possession of the United States shall be deemed...

  3. Mental illness complicated by the santeria belief in spirit possession.

    Science.gov (United States)

    Alonso, L; Jeffrey, W D

    1988-11-01

    Santeria, a religious system that blends African and Catholic beliefs, is practiced by many Cuban Americans. One aspect of this system is the belief in spirit possession. Basic santeria beliefs and rituals, including the fiesta santera (a gathering at which some participants may become possessed), are briefly described, and four cases in which the patients' belief in possession played a role in their mental illness are presented. The belief in possession can complicate the diagnosis and treatment of mental illness, but it should not be considered a culture-bound syndrome. Rather, it may be a nonspecific symptom of a variety of mental illnesses and should be evaluated in the context of the patient's overall belief system and ability to carry out usual activities.

  4. Criminalization of 'Possession of Unexplained Property' and the ...

    African Journals Online (AJOL)

    Worku_Y

    government operating costs, increases government spending for wages and ... revenues by plundering revenue generating agencies such as tax collection, ..... a) the assets under the ownership or possession of himself and his family; and.

  5. Liposomal Drug Delivery of Anticancer Agents

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob

    and retention (EPR) effect. The liposomes consists of sPLA2 IIA sensitive phospholipids having anticancer drugs covalently attached to the sn-2 position of the glycerol backbone in the phospholipids, hence drug leakage is avoided from the carrier system. Various known anticancer agents, like chlorambucil, all......) based strategy using a limited number of reaction types. Upon coupling of unsaturated building blocks ring closing metathesis cascades were used to “reprogram” the molecular scaffold and highly diverse structures were obtained. In total 20 novel compounds with a broad structural diversity were prepared...

  6. Synthesis and evaluation of cardiac glycoside mimics as potential anticancer drugs

    DEFF Research Database (Denmark)

    Jensen, Marie; Schmidt, Steffen; Fedosova, Natalya

    2011-01-01

    recent years cardiac glycosides have furthermore been suggested to possess valuable anticancer activity. To mimic the labile trisaccharide of digitoxin with a stabile carbohydrate surrogate, we have used sulfur linked ethylene glycol moieties of varying length (mono-, di-, tri- or tetra-ethylene glycol...... the shortest mimics were found to have highest efficacy, with the best ligand having a monoethylene glycol unit (IC(50) 0.24 μM), which was slightly better than digitoxigenin (IC(50) 0.64 μM), while none of the novel cardiac glycoside mimics display an in vitro effect as high as digitoxin (IC(50) 0.02 μM)....

  7. Chemical constituents and anticancer effects of the essential oil from leaves of Xylopia laevigata.

    Science.gov (United States)

    Quintans, Jullyana de S S; Soares, Bruno M; Ferraz, Rosana P C; Oliveira, Allan C A; da Silva, Thanany B; Menezes, Leociley R A; Sampaio, Marília F C; Prata, Ana Paula do N; Moraes, Manoel O; Pessoa, Claudia; Antoniolli, Angelo R; Costa, Emmanoel V; Bezerra, Daniel P

    2013-01-01

    Xylopia laevigata, popularly known as "meiú" and "pindaíba", is a medicinal plant used in the folk medicine of the Brazilian Northeast for several purposes. The chemical constituents of the essential oil from leaves of X. laevigata, collected from wild plants growing at three different sites of the remaining Atlantic forest in Sergipe State (Brazilian Northeast), were analyzed by GC/FID and GC/MS. The effect of the essential oil samples was assessed on tumor cells in culture, as well on tumor growth in vivo. All samples of the essential oil were dominated by sesquiterpene constituents. A total of 44 compounds were identified and quantified. Although some small differences were observed in the chemical composition, the presence of γ-muurolene (0.60-17.99%), δ-cadinene (1.15-13.45%), germacrene B (3.22-7.31%), α-copaene (3.33-5.98%), germacrene D (9.09-60.44%), bicyclogermacrene (7.00-14.63%), and (E)-caryophyllene (5.43-7.98%) were verified as major constituents in all samples of the essential oil. In the in vitro cytotoxic study, the essential oil displayed cytotoxicity to all tumor cell lines tested, with the different samples displaying a similar profile; however, they were not hemolytic or genotoxic. In the in vivo antitumor study, tumor growth inhibition rates were 37.3-42.5%. The treatment with the essential oil did not significantly affect body weight, macroscopy of the organs, or blood leukocyte counts. In conclusion, the essential oil from the leaves of X. laevigata is chemically characterized by the presence of γ-muurolene, δ-cadinene, germacrene B, α-copaene, germacrene D, bicyclogermacrene, and (E)-caryophyllene as major constituents and possesses significant in vitro and in vivo anticancer potential. Georg Thieme Verlag KG Stuttgart · New York.

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

    African Journals Online (AJOL)

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

  9. Anticancer and antiproliferative activity of natural brassinosteroids

    Czech Academy of Sciences Publication Activity Database

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

    2008-01-01

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

  10. Anticancer Drugs from Marine Flora: An Overview

    OpenAIRE

    Sithranga Boopathy, N.; Kathiresan, K.

    2010-01-01

    Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharide...

  11. Optimization of gefitinib analogues with potent anticancer activity.

    Science.gov (United States)

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

    2014-11-15

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

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

    Directory of Open Access Journals (Sweden)

    Wajaht A. Shah

    2014-05-01

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

  13. Possessive Pronouns in European Portuguese and Old French

    Directory of Open Access Journals (Sweden)

    Matilde Miguel

    2002-12-01

    Full Text Available The aim of this paper is to bring European Portuguese (EP data into light, showing that, in spite of the lack of morphological evidence, the syntactic behaviour of possessives, across EP dialects, shows evidences for a tripartite possessive system (Cardinaletti, 1998; Cardinaletti & Starke, 1999. It will be argued that the syntactic position of possessives parallels the positions assumed for EP sentential subjects in non interrogative contexts: [Spec, AgrsP], [Spec, TP] and [Spec, VP]. As a matter of fact, depending on their syntactic properties and assuming, as null hypothesis, that the nominal head moves to Numb'º', possessives may occur in [Spec, AgrsNP], [Spec, NumbP] and [Spec, NP]. Furthermore, would it be so, this dialectal variation would be useful in order to understand the changes that have occurred in other romance languages in previous stages. It might be the case that the loss of weak possessive forms (“mien” in French parallels, among other things, the lack of sentential subjects in [Spec, TP].

  14. The goalkeeper influence on ball possession effectiveness in futsal

    Directory of Open Access Journals (Sweden)

    Vicente-Vila Pedro

    2016-06-01

    Full Text Available The aim of this study was to identify which variables were the best predictors of success in futsal ball possession when controlling for space and task related indicators, situational variables and the participation of the goalkeeper as a regular field player or not (5 vs. 4 or 4 vs. 4. The sample consisted of 326 situations of ball possession corresponding to 31 matches played by a team from the Spanish Futsal League during the 2010–2011, 2011–2012 and 2012–2013 seasons. Multidimensional qualitative data obtained from 10 ordered categorical variables were used. Data were analysed using chi-square analysis and multiple logistic regression analysis. Overall, the highest ball possession effectiveness was achieved when the goalkeeper participated as a regular field player (p<0.01, the duration of the ball possession was less than 10 s (p<0.01, the ball possession ended in the penalty area (p<0.01 and the defensive pressure was low (p<0.01. The information obtained on the relative effectiveness of offensive playing tactics can be used to improve team’s goal-scoring and goal preventing abilities.

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

    Directory of Open Access Journals (Sweden)

    Milind K. Choudhari

    2013-01-01

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

  16. Glycosides from Medicinal Plants as Potential Anticancer Agents: Emerging Trends towards Future Drugs.

    Science.gov (United States)

    Khan, Haroon; Saeedi, Mina; Nabavi, Seyed Mohammad; Mubarak, Mohammad S; Bishayee, Anupam

    2018-04-03

    Cancer continues to be a global burden, despite the advancement of various technological and pharmaceutical improvements over the past two decades. Methods for treating cancer include surgery, radiotherapy and chemotherapy in addition to other specialized techniques. On the other hand, medicinal plants have been traditionally employed either as the complementary medicine or dietary agents in the treatment and management of cancer. Medicinal plants are a rich source of secondary metabolites with interesting biological and pharmacological activities. Among these metabolites, glycosides are naturally occurring substances and have outstanding therapeutic potential and clinical utility. Different medical research engines such GoogleScholar, PubMed, SpringerLink, ScienceDirect were used to collect related literature on the subject matter. In this regard, only peer reviewed journals were considered. Emerging results showed that numerous glycosides isolated from various plants possessed marked anticancer activity against a variety of cancer cell lines. Accordingly, the aim of the present review is to shed light on the anticancer effects of glycosides, analyze possible mechanisms of action, and highlight the role of these natural agents as complementary and alternative medicine in combating and managing cancer. The glycosides isolated from different plants demonstrated potent cytotoxic effects against various cancer cell lines in initial preclinical studies. The anticancer effect was mediated through multiple mechanisms; however further detail studies are needed to understand the full potential of glycosides for clinical utility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Synthesis of novel naphthoquinone aliphatic amides and esters and their anticancer evaluation.

    Science.gov (United States)

    Kongkathip, Boonsong; Akkarasamiyo, Sunisa; Hasitapan, Komkrit; Sittikul, Pichamon; Boonyalai, Nonlawat; Kongkathip, Ngampong

    2013-02-01

    Fourteen new naphthoquinone aliphatic amides and seventeen naphthoquinone aliphatic esters were synthesized in nine to ten steps from 1-hydroxy-2-naphthoic acid with 9-25% overall yield for the amides, and 16-21% overall yield for the esters. The key step of the amide synthesis is a coupling reaction between amine and various aliphatic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling agent while for the ester synthesis, DCC/DMAP or CDI was used as the coupling reagent between aliphatic acids and naphthoquinone alcohol. Both naphthoquinone amides and esters were evaluated for their anticancer activity against KB cells. It was found that naphthoquinone aliphatic amides showed stronger anticancer activity than those of the esters when the chains are longer than 7-carbon atoms. The optimum chain of amides is expected to be 16-carbon atoms. In addition, naphthoquinone aliphatic esters with α-methyl on the ester moiety possessed much stronger anticancer activity than the straight chains. Decatenation assay revealed that naphthoquinone amide with 16-carbon atoms chain at 15 μM and 20 μM can completely inhibit hTopoIIα activity while at 10 μM the enzyme activity was moderately inhibited. Molecular docking result also showed the same trend as the cytotoxicity and decatenation assay. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Peter A. Ajibade

    2013-09-01

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

  19. Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe₃O₄-PEG-GA) Against Lung, Breast and Colon Cancer Cells.

    Science.gov (United States)

    Rosman, Raihana; Saifullah, Bullo; Maniam, Sandra; Dorniani, Dena; Hussein, Mohd Zobir; Fakurazi, Sharida

    2018-02-02

    Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer, antioxidant and anti-inflammatory properties. In this study we have redesigned our previously reported anticancer nanocomposite formulation with improved drug loading based on iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with anticancer drug gallic acid (Fe₃O₄-PEG-GA). The in vitro release profile and percentage drug loading were found to be better than our previously reported formulation. The anticancer activity of pure gallic acid (GA), empty carrier (Fe₃O₄-PEG) nanocarrier and of anticancer nanocomposite (Fe₃O₄-PEG-GA) were screened against human lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HT-29) and normal fibroblast cells (3T3) after incubation of 24, 48 and 72 h using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The designed formulation (Fe₃O₄-PEG-GA) showed better anticancer activity than free gallic acid (GA). The results of the in vitro studies are highly encouraging to conduct the in vivo studies.

  20. Themes in Spirit Possession in Ugandan Christianity | James ...

    African Journals Online (AJOL)

    . This paper discerns a number of common themes that run through many of these experiences. In particular, sex as a motif for deviance and evil is noted as a common feature of many of the possession stories and all contact with spirits is seen ...

  1. Gun Possession among Massachusetts Batterer Intervention Program Enrollees

    Science.gov (United States)

    Rothman, Emily F.; Johnson, Renee M.; Hemenway, David

    2006-01-01

    Batterers with access to firearms present a serious lethal threat to their partners. The purpose of this exploratory study is to estimate the prevalence of and risk markers for gun possession among Massachusetts men enrolled in batterer intervention programs. The authors found that 1.8% of the men reported having a gun in or around their home.…

  2. Licenses for possessing and applying radioactive sources, materials, etc

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    Commercial and governmental institutions have been licensed by Dutch authorities to possess and apply radioactive sources, materials, etc. A summary is given and the list is subdivided into a number of sections such as radioactive sources, radioactive materials, X-ray equipment and technetium-generators

  3. 46 CFR 308.504 - Definition of territories and possessions.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Definition of territories and possessions. 308.504 Section 308.504 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance I-Introduction § 308.504 Definition of territories and...

  4. Evidence of vanillin binding to CAMKIV explains the anti-cancer mechanism in human hepatic carcinoma and neuroblastoma cells.

    Science.gov (United States)

    Naz, Huma; Tarique, Mohd; Khan, Parvez; Luqman, Suaib; Ahamad, Shahzaib; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2018-01-01

    Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr kinase family, and is associated with different types of cancer and neurodegenerative diseases. Vanillin is a natural compound, a primary component of the extract of the vanilla bean which possesses varieties of pharmacological features including anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor. Here, we have investigated the binding mechanism and affinity of vanillin to the CAMKIV which is being considered as a potential drug target for cancer and neurodegenerative diseases. We found that vanillin binds strongly to the active site cavity of CAMKIV and stabilized by a large number of non-covalent interactions. We explored the utility of vanillin as anti-cancer agent and found that it inhibits the proliferation of human hepatocyte carcinoma (HepG2) and neuroblastoma (SH-SY5Y) cells in a dose-dependent manner. Furthermore, vanillin treatment resulted into the significant reduction in the mitochondrial membrane depolarization and ROS production that eventually leads to apoptosis in HepG2 and SH-SY5Y cancer cells. These findings may offer a novel therapeutic approach by targeting the CAMKIV using natural product and its derivative with a minimal side effect.

  5. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

    Science.gov (United States)

    Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

    2016-08-01

    Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

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

    Science.gov (United States)

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

    2017-12-04

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

  7. Transportan 10 improves the anticancer activity of cisplatin.

    Science.gov (United States)

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

    2016-05-01

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

  8. Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents.

    Science.gov (United States)

    Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while

  9. Some medicinal plants as natural anticancer agents

    OpenAIRE

    Govind Pandey; S Madhuri

    2009-01-01

    India is the largest producer of medicinal plants and is rightly called the "Botanical garden of the World". The medicinal plants, besides having natural therapeutic values against various diseases, also provide high quality of food and raw materials for livelihood. Considerable works have been done on these plants to treat cancer, and some plant products have been marketed as anticancer drugs, based on the traditional uses and scientific reports. These plants may promote host resistance agai...

  10. Proteomics of anti-cancer drugs

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Hana; Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Hajdůch, M.; Gadher, S. J.

    2009-01-01

    Roč. 276, Supplement 1 (2009), s. 84-84 E-ISSN 1742-4658. [34th FEBS Congress. 04.07.2009-09.07.2009, Praha] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : proteomics * anti-cancer drugs * biomarkers Subject RIV: FD - Oncology ; Hematology

  11. Histone Deacetylase Inhibitors as Anticancer Drugs.

    Science.gov (United States)

    Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

    2017-07-01

    Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  12. Histone Deacetylase Inhibitors as Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Tomas Eckschlager

    2017-07-01

    Full Text Available Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC and histone acetyltransferases (HAT. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  13. Anticancer Drugs from Marine Flora: An Overview

    Directory of Open Access Journals (Sweden)

    N. Sithranga Boopathy

    2010-01-01

    Full Text Available Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. The chemicals have displayed an array of pharmacological properties especially antioxidant, immunostimulatory, and antitumour activities. The phytochemicals possibly activate macrophages, induce apoptosis, and prevent oxidative damage of DNA, thereby controlling carcinogenesis. In spite of vast resources enriched with chemicals, the marine floras are largely unexplored for anticancer lead compounds. Hence, this paper reviews the works so far conducted on this aspect with a view to provide a baseline information for promoting the marine flora-based anticancer research in the present context of increasing cancer incidence, deprived of the cheaper, safer, and potent medicines to challenge the dreadful human disease.

  14. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

    Science.gov (United States)

    Rayan, Anwar; Raiyn, Jamal; Falah, Mizied

    2017-01-01

    Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

  15. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

    Directory of Open Access Journals (Sweden)

    Anwar Rayan

    Full Text Available Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

  16. Antimalarial activity of abietane ferruginol analogues possessing a phthalimide group.

    Science.gov (United States)

    González, Miguel A; Clark, Julie; Connelly, Michele; Rivas, Fatima

    2014-11-15

    The abietane-type diterpenoid (+)-ferruginol, a bioactive compound isolated from New Zealand's Miro tree (Podocarpus ferruginea), displays relevant pharmacological properties, including antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and anticancer. Herein, we demonstrate that ferruginol (1) and some phthalimide containing analogues 2-12 have potential antimalarial activity. The compounds were evaluated against malaria strains 3D7 and K1, and cytotoxicity was measured against a mammalian cell line panel. A promising lead, compound 3, showed potent activity with an EC50 = 86 nM (3D7 strain), 201 nM (K1 strain) and low cytotoxicity in mammalian cells (SI>290). Some structure-activity relationships have been identified for the antimalarial activity in these abietane analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Abidemi J. Akindele

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Liao W

    2016-04-01

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

  19. Challenges and strategies in anti-cancer nanomedicine development : An industry perspective

    NARCIS (Netherlands)

    Hare, Jennifer I.; Lammers, Twan|info:eu-repo/dai/nl/304824577; Ashford, Marianne B.; Puri, Sanyogitta; Storm, G|info:eu-repo/dai/nl/073356328; Barry, Simon T.

    2017-01-01

    Successfully translating anti-cancer nanomedicines from pre-clinical proof of concept to demonstration of therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient

  20. Challenges and strategies in anti-cancer nanomedicine development: An industry perspective

    NARCIS (Netherlands)

    Hare, J.I.; Lammers, Twan Gerardus Gertudis Maria; Ashford, M.B.; Puri, S.; Storm, Gerrit; Barry, S.T.

    2017-01-01

    Successfully translating anti-cancer nanomedicines from pre-clinical proof of concept to demonstration of therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient

  1. Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications.

    Science.gov (United States)

    Deslouches, Berthony; Di, Y Peter

    2017-07-11

    In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs.

  2. The anticancer effects of Resina Draconis extract on cholangiocarcinoma.

    Science.gov (United States)

    Wen, Feng; Zhao, Xiangxuan; Zhao, Yun; Lu, Zaiming; Guo, Qiyong

    2016-11-01

    Cholangiocarcinoma (CCA) is a relatively rare, heterogeneous malignant tumor with poor clinical outcomes. Because of high insensitivity to chemotherapy and radiotherapy, there are no effective treatment options. Efforts to identify and develop new agents for prevention and treatment of this deadly disease are urgent. Here, we assessed the apoptotic cytotoxicity of Resina Draconis extract (RDE) using in vitro and in vivo assays and identified the mechanisms underlying antitumor effects of RDE. RDE was obtained via vacuum distillation of Resina Draconis with 75 % ethanol. The ethanol extract could inhibit CCA cell proliferation and trigger apoptotic cell death in both QBC939 and HCCC9810 cell lines in a time- and concentration-dependent manner. RDE treatment resulted in intracellular caspase-8 and poly (ADP-ribose) polymerase protease activation. RDE significantly downregulated antiapoptotic protein survivin expression and upregulated proapoptotic protein Bak expression. RDE also inhibited CCA tumor growth in vivo. We observed that human CCA tissues had much higher survivin expression than did paired adjacent normal tissue. Taken together, the current data suggested that RDE has anticancer effects on CCA, and that RDE could function as a novel anticancer agent to benefit patients with CCA.

  3. AlgiMatrix™ based 3D cell culture system as an in-vitro tumor model for anticancer studies.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available Three-dimensional (3D in-vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in-vivo conditions. Taking the advantages of 3D culture, we have developed the in-vitro tumor model for anticancer drug screening.Cancer cells grown in 6 and 96 well AlgiMatrix™ scaffolds resulted in the formation of multicellular spheroids in the size range of 100-300 µm. Spheroids were grown in two weeks in cultures without compromising the growth characteristics. Different marketed anticancer drugs were screened by incubating them for 24 h at 7, 9 and 11 days in 3D cultures and cytotoxicity was measured by AlamarBlue® assay. Effectiveness of anticancer drug treatments were measured based on spheroid number and size distribution. Evaluation of apoptotic and anti-apoptotic markers was done by immunohistochemistry and RT-PCR. The 3D results were compared with the conventional 2D monolayer cultures. Cellular uptake studies for drug (Doxorubicin and nanoparticle (NLC were done using spheroids.IC(50 values for anticancer drugs were significantly higher in AlgiMatrix™ systems compared to 2D culture models. The cleaved caspase-3 expression was significantly decreased (2.09 and 2.47 folds respectively for 5-Fluorouracil and Camptothecin in H460 spheroid cultures compared to 2D culture system. The cytotoxicity, spheroid size distribution, immunohistochemistry, RT-PCR and nanoparticle penetration data suggested that in vitro tumor models show higher resistance to anticancer drugs and supporting the fact that 3D culture is a better model for the cytotoxic evaluation of anticancer drugs in vitro.The results from our studies are useful to develop a high throughput in vitro tumor model to study the effect of various anticancer agents and various molecular pathways affected by the anticancer drugs and formulations.

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

    Directory of Open Access Journals (Sweden)

    Xianjun Fu

    2017-01-01

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

  5. Descending with Angels: Jinn Possession, Islamic Exorcism, and Psychiatry

    DEFF Research Database (Denmark)

    Suhr, Christian

    What is it like to be a Muslim possessed by a jinn spirit? How do you find refuge from madness and evil in a place like Denmark? In this book I explore some of the ways in which Muslims in the West have sought to protect themselves. Over several years I followed Muslim patients being treated.......” In the book I analyze how these broader social and political issues are paralleled in the invisible dynamics of jinn possession and psychosis, proposing new theoretical perspectives on religious and psychiatric healing as ritual practices for dealing with the invisible in human life....... hypervisible in public discourse through intensive state monitoring, surveillance, and media coverage. Yet their religion of Islam remains poorly understood and is frequently identified by politicians, commentators, and even healthcare specialists as the underlying invisible cause of “integration problems...

  6. The Regulation of the Possession of Weapons at Gatherings

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    Pieter du Toit

    2013-12-01

    Full Text Available The Dangerous Weapons Act 15 of 2013 provides for certain prohibitions and restrictions in respect of the possession of a dangerous weapon and it repeals the Dangerous Weapons Act 71 of 1968 as well as the different Dangerous Weapons Acts in operation in the erstwhile TBVC States. The Act also amends the Regulation of Gatherings Act 205 of 1993 to prohibit the possession of any dangerous weapon at a gathering or demonstration. The Dangerous Weapons Act provides for a uniform system of law governing the use of dangerous weapons for the whole of South Africa and it furthermore no longer places the onus on the individual charged with the offence of the possession of a dangerous weapon to show that he or she did not have any intention of using the firearm for an unlawful purpose. The Act also defines the meaning of a dangerous weapon. According to our court’s interpretation of the Dangerous Weapons Act 71 of 1968 a dangerous weapon was regarded as an object used or intended to be used as a weapon even if it had not been designed for use as a weapon. The Act, however, requires the object to be capable of causing death or inflicting serious bodily harm if it were used for an unlawful purpose. The possession of a dangerous weapon, in circumstances which may raise a reasonable suspicion that the person intends to use it for an unlawful purpose, attracts criminal liability. The Act also provides a useful set of guidelines to assist courts to determine if a person charged with the offence of the possession of a dangerous weapon had indeed intended to use the weapon for an unlawful purpose. It seems, however, that the Act prohibits the possession of a dangerous weapon at gatherings, even if the person carrying the weapon does not intend to use it for an unlawful purpose. The state will, however, have to prove that the accused had the necessary control over the object and the intention to exercise such control, as well as that the object is capable of

  7. Evaluation of anticancer effects of a novel proteasome inhibitor (Velcade), interferon (alpha-interferon) and anti myeloma antibodies on the growth of myeloma cells

    International Nuclear Information System (INIS)

    El shershaby, H.M.M.

    2013-01-01

    Cancer is an abnormal growth of cells caused by multiple changes in gene expression leading to deregulated balance of cell proliferation and cell death and ultimately evolving into a population of cells that can invade tissues and metastasize to distant sites, causing significant morbidity. Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow leading to impaired hematopoiesis and bone diseases, which includes mainly lytic lesions, pathological fractures, hypercalcaemia and osteoporosis. Chemotherapy is the systemic treatment of cancer with anticancer drugs. Chemotherapy uses powerful drugs that work by slowing or stopping the cancer cells from growing, spreading or multiplying to other parts of the body. Extensive studies were run all over the world during the last years to discovery some new drugs which possess anticancer effect with less toxicity and have the ability to increase the survival time. In the current study Bortezomib was employed as chemotherapeutic drug for the treatment of myeloma cells where a variable dose of Bortezomib (5, 10,20,30,50 and 100 nM/ml) were used for treatment of myeloma cells in vitro. The results obtained indicated that the T.C/ml was decreased by increasing the drug conc. compared to that of control group. These results illustrated the effect of Bortezomib on the growth of myeloma cells, where the myeloma cell division was decreased while the older cells were deteriorated so that the T.C/ml were decreased. Also the viability of myeloma cells were significantly decreased after 72 hours of addition at drug concentration 20, 30, 50 and 100 nM/ml).

  8. Anticancer potential of Hericium erinaceus extracts against particular human cancer cell lines

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    Younis AM

    2017-06-01

    Full Text Available Cancer is a leading cause of death worldwide. Cancer resulted in 8.2 million human deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2013 to 22 million within the next two decades. Mushrooms are extensively used as nutritional supplements in many countries. Moreover, mushrooms have many medicinal properties, including anticancer activity. In this study, the anticancer activity of different polar and non-polar extracts of Hericium erinaceus were evaluated against different human cancer cell lines including human liver carcinoma (Hep G2, the human colonic epithelial carcinoma (HCT 116, the human cervical cancer cells (HeLa and the human breast adenocarcinoma (MCF-7 using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Furthermore, as a control, the cytotoxicity effect of the different extracts were tested against isolated mouse hepatocytes. It was observed that the extracts by water and methanol from fresh and lyophilized fruiting bodies of H. erinaceus had the strongest anticancer effect. In contrast, the extracts by ether and ethyl acetate from mycelia and broth of H. erinaceus showed lower anticancer activity against the tested carcinoma cell lines. The highest anticancer activity was recorded for aqueous extract of lyophilized fruiting bodies with half maximal inhibitory concentration (IC50 values of 6.1±0.2, 5.1±0.1, 5.7±0.2 and 5.8±0.3 µg/ml against Hep G2, HCT 116, HeLa and MCF-7 cells, respectively with non-significant effect on the normal mouse hepatocytes. To summarise, polar extracts of H. erinaceus can be good sources for isolating natural anticancer compounds. I recommend further chemical studies to isolate the active principles of the extract of H. erinaceus evaluated in the present.

  9. Essential oils from Egyptian aromatic plants as antioxidant and novel anticancer agents in human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ramadan, M. M.

    2015-06-01

    Full Text Available Inhibitors of tumor growth using extracts from aromatic plants are rapidly emerging as important new drug candidates for cancer therapy. The cytotoxicity and in vitro anticancer evaluation of the essential oils from thyme, juniper and clove has been assessed against five different human cancer cell lines (liver HepG2, breast MCF-7, prostate PC3, colon HCT116 and lung A549. A GC/MS analysis revealed that α-pinene, thymol and eugenol are the major components of Egyptian juniper, thyme and clove oils with concentrations of 31.19%, 79.15% and 82.71%, respectively. Strong antioxidant profiles of all the oils are revealed in vitro by DPPH and β-carotene bleaching assays. The results showed that clove oil was similarly potent to the reference drug, doxorubicin in prostate, colon and lung cell lines. Thyme oil was more effective than the doxorubicin in breast and lung cell lines while juniper oil was more effective than the doxorubicin in all the tested cancer cell lines except prostate cancer. In conclusion, the essential oils from Egyptian aromatic plants can be used as good candidates for novel therapeutic strategies for cancer as they possess significant anticancer activity.Los inhibidores de crecimiento de tumores usando extractos de plantas aromáticas están emergiendo con rapidez como nuevos e importantes medicamentos para el tratamiento del cáncer. La citotoxicidad y la acción anticancerígena in vitro de aceites esenciales de tomillo, enebro y clavo han sido evaluadas en cinco líneas celulares de cáncer humano (hígado HepG2, mama MCF-7, próstata PC3, colon HCT116 y pulmón A549. Los análisis de GC/MS mostraron que α-pineno, timol y eugenol son los principales componentes de los aceites egipcios de enebro, tomillo y clavo, con concentraciones de 31,19%, 79,15% y 82,71%, respectivamente. Se demuestra, mediante ensayos in vitro de blanqueo de DPPH y β-caroteno, el enérgico perfil antioxidante de todos los aceites. Los resultados

  10. Current situation and future usage of anticancer drug databases.

    Science.gov (United States)

    Wang, Hongzhi; Yin, Yuanyuan; Wang, Peiqi; Xiong, Chenyu; Huang, Lingyu; Li, Sijia; Li, Xinyi; Fu, Leilei

    2016-07-01

    Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.

  11. Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery.

    Science.gov (United States)

    Barbero, Margherita; Artuso, Emma; Prandi, Cristina

    2018-01-01

    Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Oral anticancer agent medication adherence by outpatients.

    Science.gov (United States)

    Kimura, Michio; Usami, Eiseki; Iwai, Mina; Nakao, Toshiya; Yoshimura, Tomoaki; Mori, Hiromi; Sugiyama, Tadashi; Teramachi, Hitomi

    2014-11-01

    In the present study, medication adherence and factors affecting adherence were examined in patients taking oral anticancer agents. In June 2013, 172 outpatients who had been prescribed oral anticancer agents by Ogaki Municipal Hospital (Ogaki, Gifu, Japan) completed a questionnaire survey, with answers rated on a five-point Likert scale. The factors that affect medication adherence were evaluated using a customer satisfaction (CS) analysis. For patients with good and insufficient adherence to medication, the median ages were 66 years (range, 21-85 years) and 73 years (range, 30-90 years), respectively (P=0.0004), while the median dosing time was 131 days (range, 3-3,585 days) and 219 days (24-3,465 days), respectively (P=0.0447). In 36.0% (62 out of 172) of the cases, there was insufficient medication adherence; 64.5% of those cases (40 out of 62) showed good medication compliance (4-5 point rating score). However, these patients did not fully understand the effects or side-effects of the drugs, giving a score of three points or less. The percentage of patients with good medication compliance was 87.2% (150 out of 172). Through the CS analysis, three items, the interest in the drug, the desire to consult about the drug and the condition of the patient, were extracted as items for improvement. Overall, the medication compliance of the patients taking the oral anticancer agents was good, but the medication adherence was insufficient. To improve medication adherence, a better understanding of the effectiveness and necessity of drugs and their side-effects is required. In addition, the interest of patients in their medication should be encouraged and intervention should be tailored to the condition of the patient. These steps should lead to improved medication adherence.

  13. Artemisinin–Second Career as Anticancer Drug?

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2015-10-01

    Full Text Available Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood (qinhao, Artemisia annua L. represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron reacts with artemisinin, which leads to the formation of reactive oxygen species and ultimately to a plethora anticancer effects of artemisinins, e.g. expression of antioxidant response genes, cell cycle arrest (G1 as well as G2 phase arrests, DNA damage that is repaird by base excision repair, homogous recombination and non-homologous end-joining, as well as different modes of cell death (intrinsic and extrinsic apoptosis, autophagy, necrosis, necroptosis, oncosis, and ferroptosis. Furthermore, artemisinins inhibit neoangiogenesis in tumors. The signaling of major transcription factors (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc. and signaling pathways are affected by artemisinins (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, nitric oxide signaling, and others. Several case reports on the compassionate use of artemisinins as well as clinical Phase I/II pilot studies indicate the clinical activity of artemisinins in veterinary and human cancer patients. Larger scale of Phase II and III clinical studies are required now to further develop artemisinin-type compounds as novel anticancer drugs.

  14. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

    Directory of Open Access Journals (Sweden)

    Ververis K

    2013-02-01

    Full Text Available Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,*1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, Australia*These authors contributed equally to this workAbstract: Histone deacetylase (HDAC inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza and depsipeptide (romidepsin, Istodax. More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the

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

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    Jiaolin Bao

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

  16. Relationship between length of A-bomb survivor's health handbook possession and mortality risk

    International Nuclear Information System (INIS)

    Otani, Keiko; Ohtaki, Megu; Satoh, Kenichi; Tonda, Tetsuji

    2012-01-01

    The title handbook was first issued to support the health of A-bomb survivors by Japan MHLW in 1957, and about 220 thousands possess it in 2010. Its major supports contain free medicare, 2 periodic and 2 optional medical examinations/year and other various benefits. This study was performed to elucidate the relationship in the title for evaluation of its life prolonging effect on Hiroshima survivors. The length of handbook possession was defined the period from acquiring it to death. The cohort was 17,335 (7,607 men) registered survivors who had had the handbook for 1 year or more, and before Nov. 1965 or later, until Dec. 2010. Causes of death event were classified to be the cerebrovascular, cardiac and cancerous disease, and others were censored. The objective variable was mortality risk, and predictors were the exposed dose, age at the exposure, chronological age and length of handbook possession. Risk of cerebrovascular or cardiac death was estimated by the model of exponential function, and of cancer death, of power function based on multi-stage theory of carcinogenesis. Results revealed that the cerebrovascular mortality of women and men was 8.1 and 7.2%, respectively; cardiac, 8.7 and 7.2%; and cancerous, 10.1 and 14.9%. Significant reduction of relative risk of cerebrovascular death, about 4% per 1 year handbook possession, was observed in men alone; negative correlations of period effect were seen in cerebrovascular and cardiac death of women; and positive correlation between cancer death and exposed dose was observed. The prophylaxis and continuous treatment of cerebrovascular disease due to the handbook possession were thought effective in men. (T.T.)

  17. The investigation of crimes refering to forgery of documents and possession of forged documents

    OpenAIRE

    Kotovienė, Danutė

    2011-01-01

    THE INVESTIGATION OF CRIMES REFERING TO FORGERY OF DOCUMENTS AND POSSESSION OF FORGED DOCUMENTS Constantly improving informational technologies more and more get into our daily routine: nowadays it is widely spread internet payments, purchases, signing on-line agreements using electronic signatures. However, paper documents or other made of appropriate materials, which have material evidence, still have a very significant impact on our life. Its convey different aspects of states’ public work...

  18. Are community pharmacists equipped to ensure the safe use of oral anticancer therapy in the community setting? Results of a cross-country survey of community pharmacists in Canada.

    Science.gov (United States)

    Abbott, Rick; Edwards, Scott; Whelan, Maria; Edwards, Jonathan; Dranitsaris, George

    2014-02-01

    Oral anticancer agents offer significant benefits over parenteral anticancer therapy in terms of patient convenience and reduced intrusiveness. Oral anticancer agents give many cancer patients freedom from numerous hospital visits, allowing them to obtain their medications from their local community pharmacy. However, a major concern with increased use of oral anticancer agents is shift of responsibility in ensuring the proper use of anticancer agents from the hospital/clinical oncology team to the patient/caregiver and other healthcare providers such as the community pharmacists who may not be appropriately trained for this. This study assessed the readiness of community pharmacists across Canada to play this increased role with respect to oral anticancer agents. Using a structured electronic mailing strategy, a standardized survey was mailed to practicing pharmacists in five provinces where community pharmacists were dispensing the majority of oral anticancer agents. In addition to collecting basic demographic and their practice setting, the survey assessed the pharmacists' knowledge regarding cancer therapy and oral anticancer agents in particular, their education needs and access to resources on oral anticancer agents, the quality of prescriptions for oral anticancer agents received by them in terms of the required elements, their role in patient education, and steps to enhance patient and personal safety. There were 352 responses to the survey. Only 13.6% of respondents felt that they had received adequate oncology education at the undergraduate level and approximately 19% had attended a continuing education event related to oncology in the past 2 years. Only 24% of the pharmacists who responded were familiar with the common doses of oral anticancer agents and only 9% felt comfortable educating patients on these medications. A substantial portion of community pharmacists in Canada lack a solid understanding of oral anticancer agents and thus are poorly

  19. A review of economic impact of targeted oral anticancer medications.

    Science.gov (United States)

    Shen, Chan; Chien, Chun-Ru; Geynisman, Daniel M; Smieliauskas, Fabrice; Shih, Ya-Chen T

    2014-02-01

    There has been a rapid increase in the use of targeted oral anticancer medications (OAMs) in the past decade. As OAMs are often expensive, economic consideration play a significant role in the decision to prescribe, receive or cover them. This paper performs a systematic review of costs or budgetary impact of targeted OAMs to better understand their economic impact on the healthcare system, patients as well as payers. We present our review in a summary table that describes the method and main findings, take into account multiple factors, such as country, analytical approach, cost type, study perspective, timeframe, data sources, study population and care setting when we interpret the results from different papers, and discuss the policy and clinical implications. Our review raises a concern regarding the role of sponsorship on findings of economic analyses as the vast majority of pharmaceutical company-sponsored studies reported cost advantages toward the sponsor's drugs.

  20. Phytochemicals and Biogenic Metallic Nanoparticles as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Pasupuleti Visweswara Rao

    2016-01-01

    Full Text Available Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities.

  1. Peptides with Dual Antimicrobial and Anticancer Activities

    Science.gov (United States)

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

    2017-02-01

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

  2. CHRISTIAN SYMBOLISM IN FYODOR DOSTOEVSKY'S NOVEL "THE POSSESSED" ("DEMONS"

    Directory of Open Access Journals (Sweden)

    Sergei Leonidovich Sharakov

    2013-11-01

    Full Text Available The article raises a question of Christian symbolism in Fyodor Dostoevsky’s novel The Possessed (Demons. The introductory part identifies the purpose of a symbol in Christian poetics through the parallel with ancient symbolism. The author makes a conclusion that the functional role of a symbol in the ancient world and Christian tradition is different. Therefore, the ancient symbol involves a number of interrelated categories, such as fate, intuition or conjecture, inspiration, and predictions. Christian symbolism is based on the idea of redemption and moral innocence. Methodologically, the article is based on a cultural and historical approach, as well as on the comparative academic tradition. The overview of Dostoyevsky’s pre-materials for The Possessed (Demons enables us to suggest the use of Christian symbolism in this novel. Hence, the objective of the study is to investigate a composition of images and symbols in this piece of writing, with a special focus on the image of a chronicler since the storyline of the novel is developed through his perception. We make a supposition that there are several levels of Gospel perception in the artistic vision or consciousness of the chronicler, that form the basis of the symbolical composition of the novel. The article sequentially examines the examples of Christian symbolism, including the connection of ideas, characters and storylines of the novel with the Gospel. Then it gives evidence and reasons for the thesis that the Gospel gives the characters of the novel the grounds for shaping their destiny.

  3. Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

    Directory of Open Access Journals (Sweden)

    Heewon Park

    Full Text Available The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc. and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.

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

    Science.gov (United States)

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

    2016-04-30

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

  5. Bioactivity-Guided Isolation of Anticancer Agents from Bauhinia ...

    African Journals Online (AJOL)

    Background: Flowers of Bauhinia kockiana were investigated for their anticancer properties. Methods: Gallic acid (1), and methyl gallate (2), were isolated via bioassay-directed isolation, and they exhibited anticancer properties towards several cancer cell lines, examined using MTT cell viability assay. Pyrogallol (3) was ...

  6. Ethnomedicine Claim Directed in Silico Prediction of Anticancer ...

    African Journals Online (AJOL)

    2018-01-01

    Jan 1, 2018 ... 0.70, MACCS fingerprint), and the top 346 compounds it identified were identical to compounds with proven anticancer activity on 60 cell lines (23). Given such performance of. CDRUG, our finding can be taken as a preliminary evidence of anticancer activity by many of the medicinal plants used for treating.

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  9. Anticancer Effect of AntiMalarial Artemisinin Compounds | Das ...

    African Journals Online (AJOL)

    A PubMed search of about 127 papers on anti‑cancer effects of antimalarials has revealed that this class of drug, including other antimalarials, have several biological characteristics that include anticancer properties. ... Keywords: Anticancer agents, Antimalarials, Antitumor activity, Artemisinins, Novel chemotherapy ...

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

    Science.gov (United States)

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

    2014-10-28

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

  11. Adducin family proteins possess different nuclear export potentials.

    Science.gov (United States)

    Liu, Chia-Mei; Hsu, Wen-Hsin; Lin, Wan-Yi; Chen, Hong-Chen

    2017-05-10

    The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are actin-binding proteins that play important roles in the stabilization of membrane cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly conserved bipartite nuclear localization signal (NLS) at the carboxyl termini, but only ADD1 can localize to the nucleus. The reason for this discrepancy is not clear. To avoid the potential effect of cell-cell junctions on the distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were transiently expressed in NIH3T3 fibroblasts and their distribution in the cytoplasm and nucleus was examined by immunofluorescence staining. Several nuclear proteins were identified to interact with ADD1 by mass spectrometry, which were further verified by co-immunoprecipitation. In this study, we found that ADD1 was detectable both in the cytoplasm and nucleus, whereas ADD2 and ADD3 were detected only in the cytoplasm. However, ADD2 and ADD3 were partially (~40%) sequestered in the nucleus by leptomycin B, a CRM1/exportin1 inhibitor. Upon the removal of leptomycin B, ADD2 and ADD3 re-distributed to the cytoplasm. These results indicate that ADD2 and ADD3 possess functional NLS and are quickly transported to the cytoplasm upon entering the nucleus. Indeed, we found that ADD2 and ADD3 possess much higher potential to counteract the activity of the NLS derived from Simian virus 40 large T-antigen than ADD1. All the ADD proteins appear to contain multiple nuclear export signals mainly in their head and neck domains. However, except for the leucine-rich motif ( 377 FEALMRMLDWLGYRT 391 ) in the neck domain of ADD1, no other classic nuclear export signal was identified in the ADD proteins. In addition, the nuclear retention of ADD1 facilitates its interaction with RNA polymerase II and zinc-finger protein 331. Our results suggest that ADD2 and ADD3 possess functional NLS and shuttle between the cytoplasm and nucleus. The discrepancy in the

  12. Immobilized cells of Candida rugosa possessing fumarase activity

    Energy Technology Data Exchange (ETDEWEB)

    Yang, L.; Zhone, L.

    1980-01-01

    Immobilized cells of C. rugosa that possessed fumarase activity were prepared by different methods; the most active immobilized cells were entrapped in polyacrylamide gels. The effects of pH temperature, and divalent cations on the fumarase activity of both immobilized and native cells were the same. Mn/sup 2 +/, Mg/sup 2 +/, Ca/sup 2 +/, and Fe/sup 2 +/ did not protect the immobilized enzyme against thermal inactivation. The activity of immobilized fumarase remained constant during 91 days of storage of 4-6 degrees. The immobilized cell column was used for the continuous production of L-malic acid from 1M fumarate at 30 degrees and pH 8.5. The immobilized column operated steadily for 2 months. Half life of the immobilized fumarase at 30 degrees was 95 days.

  13. Social forces for team coordination in ball possession game

    Science.gov (United States)

    Yokoyama, Keiko; Shima, Hiroyuki; Fujii, Keisuke; Tabuchi, Noriyuki; Yamamoto, Yuji

    2018-02-01

    Team coordination is a basic human behavioral trait observed in many real-life communities. To promote teamwork, it is important to cultivate social skills that elicit team coordination. In the present work, we consider which social skills are indispensable for individuals performing a ball possession game in soccer. We develop a simple social force model that describes the synchronized motion of offensive players. Comparing the simulation results with experimental observations, we uncovered that the cooperative social force, a measure of perception skill, has the most important role in reproducing the harmonized collective motion of experienced players in the task. We further developed an experimental tool that facilitates real players' perceptions of interpersonal distance, revealing that the tool improves novice players' motions as if the cooperative social force were imposed.

  14. PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles mediated hTERT siRNA delivery for anticancer therapy.

    Science.gov (United States)

    Xie, Ying; Qiao, Hongzhi; Su, Zhigui; Chen, Minglei; Ping, Qineng; Sun, Minjie

    2014-09-01

    Lack of safe and effective delivery vehicle is the main obstacle for siRNA mediated cancer therapy. In this study, we synthesized a pH-sensitive polymer of PEG grafted carboxymethyl chitosan (PEG-CMCS) and developed anionic-charged hybrid nanoparticles of PEG-CMCS and calcium phosphate (CaP) for siRNA delivery through a single-step self-assembly method in aqueous condition. The formed nanoparticles with charge of around -8.25 mv and average diameter of 102.1 nm exhibited efficient siRNA encapsulation and enhanced colloidal and serum stability. The test in vitro indicated that the nanoparticles entered into HepG2 cells by endocytosis, and achieved endosomal escape of siRNA effectively due to the pH-responsive disassembly of nanoparticles and dissolution of CaP in the endosome. Reporter gene silencing assay showed that luciferase siRNA delivered by the anionic nanoparticles could achieve gene silencing efficacy comparable to that of conventional Lipofectamine 2000. Additionally, dramatic hTERT knockdown mediated by the anionic nanoparticles transfection induced significant apoptosis of HepG2 cells in vitro. After intravenous injection in tumor-bearing BALB/c nude mice, the nanoparticles specifically accumulated into tumor regions by EPR effect, leading to efficient and specific gene silencing sequentially. Most importantly, the nanoparticles carrying hTERT siRNA inhibited tumor growth significantly via silencing hTERT expression and inducing cells apoptosis in HepG2 tumor xenograft. Moreover, comprehensive safety studies of the nanoparticles confirmed their superior safety both in vitro and in vivo. We concluded that the PEG-CMCS/CaP hybrid anionic nanoparticles possessed potential as a safe and effective siRNA delivery system for anticancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. The possession game? A comparative analysis of ball retention and team success in European and international football, 2007-2010.

    Science.gov (United States)

    Collet, Christian

    2013-01-01

    Possession is thought of as central to success in modern football, but questions remain about its impact on positive team outcomes (Bate, 1988; Hughes & Franks, 2005; Pollard & Reep, 1997; Stanhope, 2001). Recent studies (e.g. Bloomfield, Polman, & O'Donoghue, 2005; Carling, Williams, & Reilly, 2005; James, Mellallieu, & Holley, 2002; Jones, James, & Mellalieu, 2004; Lago, 2009; Lago & Martin, 2007; Lago-Peñas & Dellal, 2010; Lago-Peñas, Lago-Ballesteros, Dellal, & Gómez, 2010; Taylor, Mellalieu, & James, 2005; Tucker, Mellalieu, James, & Taylor, 2005) that have examined these questions have often been constrained by an exclusive focus on English or Spanish domestic play. Using data from five European leagues, UEFA and FIFA tournaments, the study found that while possession time and passing predicted aggregated team success in domestic league play, both variables were poor predictors at the individual match level once team quality and home advantage were accounted for. In league play, the effect of greater possession was consistently negative; in the Champions League, it had virtually no impact. In national team tournaments, possession failed to reach significance when offensive factors were accounted for. Much of the success behind the 'possession game' was thus a function of elite teams confined in geographic and competitive space. That ball hegemony was not consistently tied to success suggests that a nuanced approach to possession is needed to account for variant strategic environments (e.g. James et al., 2002) and compels match analysts to re-examine the metric's overall value.

  16. PEGylated Silk Nanoparticles for Anticancer Drug Delivery

    DEFF Research Database (Denmark)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew

    2015-01-01

    Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of “stealth” design principals...... is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential −56 ± 5.......6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using...

  17. Silk nanoparticles—an emerging anticancer nanomedicine

    Directory of Open Access Journals (Sweden)

    F. Philipp Seib

    2017-03-01

    Full Text Available Silk is a sustainable and ecologically friendly biopolymer with a robust clinical track record in humans for load bearing applications, in part due to its excellent mechanical properties and biocompatibility. Our ability to take bottom-up and top-down approaches for the generation of silk (inspired biopolymers has been critical in supporting the evolution of silk materials and formats, including silk nanoparticles for drug delivery. Silk nanoparticles are emerging as interesting contenders for drug delivery and are well placed to advance the nanomedicine field. This review covers the use of Bombyx mori and recombinant silks as an anticancer nanomedicine, highlighting the emerging trends and developments as well as critically assessing the current opportunities and challenges by providing a context specific assessment of this multidisciplinary field.

  18. Nitric oxide: cancer target or anticancer agent?

    Science.gov (United States)

    Mocellin, Simone

    2009-03-01

    Despite the improved understanding of nitric oxide (NO) biology and the large amount of preclinical experiments testing its role in cancer development and progression, it is still debated whether NO should be considered a potential anticancer agent or instead a carcinogen. The complexity of NO effects within a cell and the variability of the final biological outcome depending upon NO levels makes it highly challenging to determine the therapeutic value of interfering with the activity of this intriguing gaseous messenger. This uncertainty has so far halted the clinical implementation of NO-based therapeutics in the field of oncology. Accordingly, only an in depth knowledge of the mechanisms leading to experimental tumor regression or progression in response to NO will allow us to exploit this molecule to fight cancer.

  19. Molecular cytotoxic mechanisms of anticancer hydroxychalcones.

    Science.gov (United States)

    Sabzevari, Omid; Galati, Giuseppe; Moridani, Majid Y; Siraki, Arno; O'Brien, Peter J

    2004-06-30

    Chalcones are being considered as anticancer agents as they are natural compounds that are particularly cytotoxic towards K562 leukemia or melanoma cells. In this study, we have investigated phloretin, isoliquiritigenin, and 10 other hydroxylated chalcones for their cytotoxic mechanisms towards isolated rat hepatocytes. All hydroxychalcones partly depleted hepatocyte GSH and oxidized GSH to GSSG. These chalcones also caused a collapse of mitochondrial membrane potential and increased oxygen uptake. Furthermore, glycolytic or citric acid cycle substrates prevented cytotoxicity and mitochondrial membrane potential collapse. The highest pKa chalcones were the most effective at collapsing the mitochondrial membrane potential which suggests that the cytotoxic activity of hydroxychalcones are likely because of their ability to uncouple mitochondria.

  20. Kefir: a powerful probiotics with anticancer properties.

    Science.gov (United States)

    Sharifi, Mohammadreza; Moridnia, Abbas; Mortazavi, Deniz; Salehi, Mahsa; Bagheri, Marzieh; Sheikhi, Abdolkarim

    2017-09-27

    Probiotics and fermented milk products have attracted the attention of scientists from various fields, such as health care, industry and pharmacy. In recent years, reports have shown that dietary probiotics such as kefir have a great potential for cancer prevention and treatment. Kefir is fermented milk with Caucasian and Tibet origin, made from the incubation of kefir grains with raw milk or water. Kefir grains are a mixture of yeast and bacteria, living in a symbiotic association. Antibacterial, antifungal, anti-allergic and anti-inflammatory effects are some of the health beneficial properties of kefir grains. Furthermore, it is suggested that some of the bioactive compounds of kefir such as polysaccharides and peptides have great potential for inhibition of proliferation and induction of apoptosis in tumor cells. Many studies revealed that kefir acts on different cancers such as colorectal cancer, malignant T lymphocytes, breast cancer and lung carcinoma. In this review, we have focused on anticancer properties of kefir.

  1. A new anticancer agent--131I BGTP

    International Nuclear Information System (INIS)

    He Jiaheng; Jiang Shubin; Wang Guanquan

    2007-12-01

    A new anticancer precursor, di-peptide[p-Boc-Gly-Tyr-NH(CH 2 ) 2 NH-PO (ONH 4 )-O-PhI*], was synthesized and labelled with 131 I using enveloped-tube technique, the labelling yield could reach 85%. Using cell coalescent method, the biological activity in vitro of the labelled compounds was evaluated, showing that the primary appetency was kept and not damaged obviously during labelling. Results on judgement of their stability, lipophilicity and toxicity demonstrated lower toxicity, higher lipophilicity and lower iodium disassociation percentage (<12% after 72 h); furthermore, a tumour-bearing animal model, was establishd successfully, on which, the biological properties of the labelled agent was studied. (authors)

  2. Designing anticancer peptides by constructive machine learning.

    Science.gov (United States)

    Grisoni, Francesca; Neuhaus, Claudia; Gabernet, Gisela; Müller, Alex; Hiss, Jan; Schneider, Gisbert

    2018-04-21

    Constructive machine learning enables the automated generation of novel chemical structures without the need for explicit molecular design rules. This study presents the experimental application of such a generative model to design membranolytic anticancer peptides (ACPs) de novo. A recurrent neural network with long short-term memory cells was trained on alpha-helical cationic amphipathic peptide sequences and then fine-tuned with 26 known ACPs. This optimized model was used to generate unique and novel amino acid sequences. Twelve of the peptides were synthesized and tested for their activity on MCF7 human breast adenocarcinoma cells and selectivity against human erythrocytes. Ten of these peptides were active against cancer cells. Six of the active peptides killed MCF7 cancer cells without affecting human erythrocytes with at least threefold selectivity. These results advocate constructive machine learning for the automated design of peptides with desired biological activities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. System engineering approach to planning anticancer therapies

    CERN Document Server

    Świerniak, Andrzej; Smieja, Jaroslaw; Puszynski, Krzysztof; Psiuk-Maksymowicz, Krzysztof

    2016-01-01

    This book focuses on the analysis of cancer dynamics and the mathematically based synthesis of anticancer therapy. It summarizes the current state-of-the-art in this field and clarifies common misconceptions about mathematical modeling in cancer. Additionally, it encourages closer cooperation between engineers, physicians and mathematicians by showing the clear benefits of this without stating unrealistic goals. Development of therapy protocols is realized from an engineering point of view, such as the search for a solution to a specific control-optimization problem. Since in the case of cancer patients, consecutive measurements providing information about the current state of the disease are not available, the control laws are derived for an open loop structure. Different forms of therapy are incorporated into the models, from chemotherapy and antiangiogenic therapy to immunotherapy and gene therapy, but the class of models introduced is broad enough to incorporate other forms of therapy as well. The book be...

  4. Fenbendazole as a potential anticancer drug.

    Science.gov (United States)

    Duan, Qiwen; Liu, Yanfeng; Rockwell, Sara

    2013-02-01

    To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes. We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens. Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia. Fenbendazole did not alter the dose-response curves for radiation or docetaxel; instead, the agents produced additive cytotoxicities. Febendazole in maximally-intensive regimens did not alter the growth of EMT6 tumors, or increase the antineoplastic effects of radiation. These studies provided no evidence that fenbendazole would have value in cancer therapy, but suggested that this general class of compounds merits further investigation.

  5. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-15

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

  7. Berberine as a promising safe anti-cancer agent - is there a role for mitochondria?

    Science.gov (United States)

    Diogo, Catia V; Machado, Nuno G; Barbosa, Inês A; Serafim, Teresa L; Burgeiro, Ana; Oliveira, Paulo J

    2011-06-01

    Metabolic regulation is largely dependent on mitochondria, which play an important role in energy homeostasis. Imbalance between energy intake and expenditure leads to mitochondrial dysfunction, characterized by a reduced ratio of energy production (ATP production) to respiration. Due to the role of mitochondrial factors/events in several apoptotic pathways, the possibility of targeting that organelle in the tumor cell, leading to its elimination is very attractive, although the safety issue is problematic. Berberine, a benzyl-tetra isoquinoline alkaloid extracted from plants of the Berberidaceae family, has been extensively used for many centuries, especially in the traditional Chinese and Native American medicine. Several evidences suggest that berberine possesses several therapeutic uses, including anti-tumoral activity. The present review supplies evidence that berberine is a safe anti-cancer agent, exerting several effects on mitochondria, including inhibition of mitochondrial Complex I and interaction with the adenine nucleotide translocator which can explain several of the described effects on tumor cells.

  8. Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems.

    Science.gov (United States)

    Popilski, Hen; Stepensky, David

    2015-05-01

    Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies. The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed. Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.

  9. Determination of anti-cancer constituents in oplopanax horridus and oplopanax elatus

    International Nuclear Information System (INIS)

    Liu, P.; Gu, Y.; Dou, D.; Kang, T.; Smith, D.

    2012-01-01

    A rapid and reliable RP-HPLC method for the analysis of 3a-hydroxylup -20(29)-ene-23,28-dioic acid and 3 alpha -hydroxylup-20(29) -ene-23, 28-dioic acid-3-O-beta-D-glucoside in leaves of Oplopanax horridus and O. elatus was established, and their contents changes between species and different cultivated places were compared. The established analysis method presented good results and could be used as a method for the quality control of leaves of O. horridus and O. elatus. Meanwhile, the inhibitory effect of 1 and 2 on human hepatoma carcinoma cell (HepG-2) were examined and their IC/sub 50/ were determined to be 41.15 mu M and 120.06 mu M indicating that the anti-cancer activity of 1 was stronger than that of its glycoside. Moreover, the inhibitions of 1 on human colon cancer cell line (HCT116), human lung carcinoma cell line (NCI-H460) and human gastric cancer cell line (MGC803) were further tested, and the IC/sub 50/ were determined to be 21.40 mu M, 22.80 mu M and 21.26 mu M, respectively. While the inhibition of 1 on human pancreatic cancer cell line (PANC-1) was insignificant, indicating 1 possessed selectivity for the anti-cancer activity. (author)

  10. Engineered Mesenchymal Stem Cells as an Anti-Cancer Trojan Horse

    Science.gov (United States)

    Nowakowski, Adam; Drela, Katarzyna; Rozycka, Justyna; Janowski, Miroslaw

    2016-01-01

    Cell-based gene therapy holds a great promise for the treatment of human malignancy. Among different cells, mesenchymal stem cells (MSCs) are emerging as valuable anti-cancer agents that have the potential to be used to treat a number of different cancer types. They have inherent migratory properties, which allow them to serve as vehicles for delivering effective therapy to isolated tumors and metastases. MSCs have been engineered to express anti-proliferative, pro-apoptotic, and anti-angiogenic agents that specifically target different cancers. Another field of interest is to modify MSCs with the cytokines that activate pro-tumorigenic immunity or to use them as carriers for the traditional chemical compounds that possess the properties of anti-cancer drugs. Although there is still controversy about the exact function of MSCs in the tumor settings, the encouraging results from the preclinical studies of MSC-based gene therapy for a large number of tumors support the initiation of clinical trials. PMID:27460260

  11. Cyclodextrin conjugated magnetic colloidal nanoparticles as a nanocarrier for targeted anticancer drug delivery

    International Nuclear Information System (INIS)

    Banerjee, Shashwat S; Chen, D.-H.

    2008-01-01

    A novel magnetic nanocarrier (CD-GAMNPs) was fabricated for targeted anticancer drug delivery by grafting cyclodextrin (CD) onto gum arabic modified magnetic nanoparticles (GAMNPs) using hexamethylene diisocyanate (HMDI) as a linker. Analyses by transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the product had a mean diameter of 17.1 nm and a mean hydrodynamic diameter of 44.1 nm. The CD grafting was confirmed by Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA) indicated that the amount of CD grafted on the GAMNPs was 16.8 mg g -1 . The study on the loading of anticancer drug all-trans-retinoic acid (retinoic acid) revealed that the newly fabricated magnetic nanocarrier possessed a considerably higher adsorption capability as compared to GAMNPs due to the special hydrophobic cavity structure of CD, which could act as a host-guest complex with retinoic acid. Furthermore, it was found that the complexation of CD-GAMNPs with retinoic acid was exothermic and the presence of a surfactant (sodium dodecyl sulfate) led to the decrease in the inclusion of retinoic acid because the linear structure of sodium dodecyl sulfate made it easier to enter the cavity of CD as compared to less linear retinoic acid. In addition, the in vitro release profile of retinoic acid from CD-GAMNPs was characterized by an initial fast release followed by a delayed release phase

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

    Science.gov (United States)

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

    2014-06-13

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

  13. In the search for new anticancer drugs XII. Synthesis and biological evaluation of spin labeled nitrosoureas.

    Science.gov (United States)

    Sosnovsky, G; Li, S W

    1985-04-15

    The spin labeled nitrosourea 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6- tetramethyl-piperidinyl)-1-nitrosourea (SLCNU, 4) and its analogues 5-7 were synthesized either by a regio-selective method or by a conventional route via the nitrosation of the spin labeled intermediates (11a-e). Nitrosation of the ureas 11a-e with dinitrogen tetraoxide resulted in better yields than those obtained with sodium nitrite. The nitrosoureas 4-8 were tested for their anticancer activity against the lymphocytic leukemia P388 in mice. Thus, either at the equal molar dose or at the dose of equal toxicity level, the SLCNU (4) was found to be more active than the clinically used CCNU (1). Unlike CCNU (1) whose LD50 is 56 mg/kg, the SLCNU (4) possesses a low toxicity (LD50 123 mg/kg). Therefore, SLCNU (4) is a promising new entry into the nitrosourea class of anticancer drugs.

  14. Analysis of the Anticancer Phytochemicals in Andrographis paniculata Nees. under Salinity Stress

    Directory of Open Access Journals (Sweden)

    Daryush Talei

    2013-01-01

    Full Text Available Salinity causes the adverse effects in all physiological processes of plants. The present study aimed to investigate the potential of salt stress to enhance the accumulation of the anticancer phytochemicals in Andrographis paniculata accessions. For this purpose, 70-day-old plants were grown in different salinity levels (0.18, 4, 8, 12, and 16 dSm−1 on sand medium. After inducing a period of 30-day salinity stress and before flowering, all plants were harvested and the data on morphological traits, proline content and the three anticancer phytochemicals, including andrographolide (AG, neoandrographolide (NAG, and 14-deoxy-11,12-didehydroandrographolide (DDAG, were measured. The results indicated that salinity had a significant effect on the aforementioned three anticancer phytochemicals. In addition, the salt tolerance index (STI was significantly decreased, while, except for DDAG, the content of proline, the AG, and NAG was significantly increased (P≤0.01. Furthermore, it was revealed that significant differences among accessions could happen based on the total dry weight, STI, AG, and NAG. Finally, we noticed that the salinity at 12 dSm−1 led to the maximum increase in the quantities of AG, NAG, and DDAG. In other words, under salinity stress, the tolerant accessions were capable of accumulating the higher amounts of proline, AG, and NAG than the sensitive accessions.

  15. Analysis of the Anticancer Phytochemicals in Andrographis paniculata Nees. under Salinity Stress

    Science.gov (United States)

    Valdiani, Alireza; Maziah, Mahmood; Saad, Mohd Said

    2013-01-01

    Salinity causes the adverse effects in all physiological processes of plants. The present study aimed to investigate the potential of salt stress to enhance the accumulation of the anticancer phytochemicals in Andrographis paniculata accessions. For this purpose, 70-day-old plants were grown in different salinity levels (0.18, 4, 8, 12, and 16 dSm−1) on sand medium. After inducing a period of 30-day salinity stress and before flowering, all plants were harvested and the data on morphological traits, proline content and the three anticancer phytochemicals, including andrographolide (AG), neoandrographolide (NAG), and 14-deoxy-11,12-didehydroandrographolide (DDAG), were measured. The results indicated that salinity had a significant effect on the aforementioned three anticancer phytochemicals. In addition, the salt tolerance index (STI) was significantly decreased, while, except for DDAG, the content of proline, the AG, and NAG was significantly increased (P ≤ 0.01). Furthermore, it was revealed that significant differences among accessions could happen based on the total dry weight, STI, AG, and NAG. Finally, we noticed that the salinity at 12 dSm−1 led to the maximum increase in the quantities of AG, NAG, and DDAG. In other words, under salinity stress, the tolerant accessions were capable of accumulating the higher amounts of proline, AG, and NAG than the sensitive accessions. PMID:24371819

  16. Radiation protective agents possessing anti-oxidative properties

    Energy Technology Data Exchange (ETDEWEB)

    Anzai, Kazunori; Ueno, Emi; Yoshida, Akira; Furuse, Masako; Ikota, Nobuo [National Inst. of Radiological Sciences, Research Center for Radiation Safety, Chiba, Chiba (Japan)

    2005-11-15

    The purpose of studies is to see mechanisms of radiation protection of agents possessing anti-oxidative properties because the initial step resulting in radiation hazard is the formation of radicals by water radiolysis. Agents were commercially available or synthesized proxyl derivatives (spin prove agents), commercially available spin-trapping agents, edaravone and TMG (a tocopherol glycoside). Mice and cultured cells were X-irradiated by Shimadzu Pantak HF-320 or 320S. Survivals of cells were determined by colony assay and of mice, to which the agents were given intraperitoneally before or after X-irradiation, within 30 days post irradiation. Plasma and marrow concentrations of proxyls were estimated by electron spin resonance (ESR) spectrometry. Mechanisms of their radiation protective effects were shown different from agent to agent. TMG was found effective even post irradiation, which suggests a possibility for a new drug development. Some (spin trapping agents and TMG), virtually ineffective at the cell level, were found effective in the whole body, suggesting the necessity of studies on their disposition and metabolism. (S.I.)

  17. Radiation protective agents possessing anti-oxidative properties

    International Nuclear Information System (INIS)

    Anzai, Kazunori; Ueno, Emi; Yoshida, Akira; Furuse, Masako; Ikota, Nobuo

    2005-01-01

    The purpose of studies is to see mechanisms of radiation protection of agents possessing anti-oxidative properties because the initial step resulting in radiation hazard is the formation of radicals by water radiolysis. Agents were commercially available or synthesized proxyl derivatives (spin prove agents), commercially available spin-trapping agents, edaravone and TMG (a tocopherol glycoside). Mice and cultured cells were X-irradiated by Shimadzu Pantak HF-320 or 320S. Survivals of cells were determined by colony assay and of mice, to which the agents were given intraperitoneally before or after X-irradiation, within 30 days post irradiation. Plasma and marrow concentrations of proxyls were estimated by electron spin resonance (ESR) spectrometry. Mechanisms of their radiation protective effects were shown different from agent to agent. TMG was found effective even post irradiation, which suggests a possibility for a new drug development. Some (spin trapping agents and TMG), virtually ineffective at the cell level, were found effective in the whole body, suggesting the necessity of studies on their disposition and metabolism. (S.I.)

  18. The possession law suit, caused by forbidden immissions

    Directory of Open Access Journals (Sweden)

    Popov Danica D.

    2015-01-01

    Full Text Available In the Serbian Law and in most of jurisdictions, there are limits on exercising the right of property. The real estate owner must refrain from activities by which the use of other real estate is being impoded through the immission of execive gasses, vapors, smoke, heat noise, tremors etc. The property ownership whose is affected by immission exceeding the set limits, has the right to request a stop of immisions which exceeded the allowed volume of immissions. In article author describes various kinds of immissions. The general feature of this law suit is that there is only discussion on the facts and not for a legal matters. Subject matter jurisdiction for the resolution of such disputes belongs to the court of general jurisdiction, while the disputes itself is a litigation. The special rule of proceedings of action of disturbance are: provisionality of the protection of possession; urgency in proceedings; initiation of proceedings; limiting of objection; prescribing temporary measures; rendering a ruling in the form of order; appeals which may be filed within a short deadline and which does not have suspensive effect (do not delay the execution of the order; revision is not allowed etc.

  19. Novel β-amyloid aggregation inhibitors possessing a turn mimic.

    Science.gov (United States)

    Hamada, Yoshio; Miyamoto, Naoko; Kiso, Yoshiaki

    2015-04-01

    Amyloid β peptide, the main component of senile plaques found in the brain of Alzheimer disease (AD) patients, is a molecular target for AD therapeutic intervention. A number of potential AD therapeutics have been reported, including inhibitors of β-secretase, γ-secretase, and Aβ aggregation, and anti-amyloid agents, such as neprilysin, insulin degrading enzyme (IDE), and Aβ antibodies. Recently, we reported potent small-sized β-secretase (BACE1) inhibitors, which could serve as anti-AD drugs. However AD is a progressive disorder, where dementia symptoms gradually worsen over several decades, and therefore may require many years to get cured. One possible way to achieve a greater therapeutic effect is through simultaneous administration of multiple drugs, similar to those used in Highly Active Anti-Retroviral Therapy (HAART) used to treat AIDS. In order to overcome AD, we took a drug discovery approach to evaluate, novel β-amyloid aggregation inhibitors. Previously, we reported that a tong-type compound possessing a turn mimic as the inhibitor of HIV-1 protease dimerization. Oligomerized amyloid β peptides contain a turn structure within the molecule. Here, we designed and synthesized novel β-amyloid aggregation inhibitors with a turn-mimic template, based on the turn conformer of the oligomerized amyloid β peptides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Formulation of curcumin delivery with functionalized single-walled carbon nanotubes: characteristics and anticancer effects in vitro.

    Science.gov (United States)

    Li, Haixia; Zhang, Nan; Hao, Yongwei; Wang, Yali; Jia, Shasha; Zhang, Hongling; Zhang, Yun; Zhang, Zhenzhong

    2014-08-01

    Single-walled carbon nanotubes (SWCNTs), an important class of artificial nanomaterials with unique physicochemical properties, were used as novel carriers of curcumin. Formulation and evaluation of curcumin-loaded SWCNTs systems for utilizing the curcumin's anticancer potential by circumventing conventional limitations of extremely low aqueous solubility and instability under physiological conditions, and combining SWCNTs photothermal therapy enabled by the strong optical absorbance of SWCNTs in the 0.8-1.4 μm resulting in excessive local heating. After functionalized SWCNTs were confirmed, they were conjugated with curcumin (SWCNT-Cur). Subsequently, the formulation was analyzed for size, zeta-potential and morphology. And the solubility, stability and release of curcumin were assessed using spectrofluorometer, and the solid state of the curcumin was determined using X-ray diffraction and UV spectroscopy. Furthermore, in PC-3 cells, photothermal response was further determined by irradiating laser after the antitumor effect of SWCNT-Cur was evaluated. SWCNTs were functionalized, and subsequent SWCNT-Cur conjugates were found to possess an average size of 170.4 nm, a zeta potential of -12.5 mV and to significantly enhance the solubility and stability of curcumin, overcoming the barriers to adequate curcumin delivery. Moreover, curcumin in SWCNT-Cur was in an amorphous form and could be rapidly released. In PC-3 cells, improved inhibition efficacy was achieved by SWCNT-Cur compared with native curcumin. Meanwhile, the SWCNTs in SWCNT-Cur served not only as scaffolds but also as thermal ablation agents, further inhibiting PC-3 cell growth. SWCNT-Cur assemblies may provide a promising delivery system for curcumin for use in cancer therapy.

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

    Science.gov (United States)

    2011-01-01

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

  2. Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder

    Directory of Open Access Journals (Sweden)

    Amrita Banerjee

    2014-01-01

    Full Text Available Mithramycin (MTR is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin – histone proteins – as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode or both histones and chromosomal DNA (dual binding mode. The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR–DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg2+. As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies.

  3. Minimalism in fabrication of self-organized nanogels holding both anti-cancer drug and targeting moiety.

    Science.gov (United States)

    Kim, Sungwon; Park, Kyong Mi; Ko, Jin Young; Kwon, Ick Chan; Cho, Hyeon Geun; Kang, Dongmin; Yu, In Tag; Kim, Kwangmeyung; Na, Kun

    2008-05-01

    Recent researches to develop nano-carrier systems in anti-cancer drug delivery have focused on more complicated design to improve therapeutic efficacy and to reduce side effects. Although such efforts have great impact to biomedical science and engineering, the complexity has been a huddle because of clinical and economic problems. In order to overcome the problems, a simplest strategy to fabricate nano-carriers to deliver doxorubicin (DOX) was proposed in the present study. Two significant subjects (i) formation of nanoparticles loading and releasing DOX and (ii) binding specificity of them to cells, were examined. Folic acid (FA) was directly coupled with pullulan (Pul) backbone by ester linkage (FA/Pul conjugate) and the degree of substitution (DS) was varied, which were confirmed by 1H NMR and UV spectrophotometry. Light scattering results revealed that the nanogels possessed two major size distributions around 70 and 270 nm in an aqueous solution. Their critical aggregation concentrations (CACs) were less than 10 microg/mL, which are lower than general critical micelle concentrations (CMCs) of low-molecular-weight surfactants. Transmission electron microscopy (TEM) images showed well-dispersed nanogel morphology in a dried state. Depending on the DS, the nanogels showed different DOX-loading and releasing profiles. The DOX release rate from FA8/Pul (with the highest DS) for 24h was slower than that from FA4/or FA6/Pul, indicating that the FA worked as a hydrophobic moiety for drug holding. Cellular uptake of the nanogels (KB cells) was also monitored by confocal microscopy. All nanogels were internalized regardless of the DS of FA. Based on the results, the objectives of this study, to suggest a new method overcoming the complications in the drug carrier design, were successfully verified.

  4. Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin.

    Science.gov (United States)

    Saavedra, Diana I; Rencher, Benjamin D; Kwon, Doo-Hyun; Smith, Stacey J; Ess, Daniel H; Andrus, Merritt B

    2018-02-16

    Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular styryl Diels-Alder reaction strategy uniquely suited to assemble the deoxypodophyllotoxin core. Density functional theory was used to analyze concerted, polar, and singlet-open-shell diradical reaction pathways, which identified a low-energy concerted [4 + 2] Diels-Alder pathway followed by a faster di-t-butylhydroxytoluene assisted [1,3]-formal hydrogen shift.

  5. Anticancer Activity of Cobra Venom Polypeptide, Cytotoxin-II, against Human Breast Adenocarcinoma Cell Line (MCF-7) via the Induction of Apoptosis

    OpenAIRE

    Ebrahim, Karim; Shirazi, Farshad H.; Vatanpour, Hosein; zare, Abas; Kobarfard, Farzad; Rabiei, Hadi

    2014-01-01

    Purpose Breast cancer is a significant health problem worldwide, accounting for a quarter of all cancer diagnoses in women. Current strategies for breast cancer treatment are not fully effective, and there is substantial interest in the identification of novel anticancer agents especially from natural products including toxins. Cytotoxins are polypeptides found in the venom of cobras and have various physiological effects. In the present study, the anticancer potential of cytotoxin-II against...

  6. Exploring the novel heterocyclic derivatives as lead molecules for design and development of potent anticancer agents.

    Science.gov (United States)

    Azad, Iqbal; Nasibullah, Malik; Khan, Tahmeena; Hassan, Firoj; Akhter, Yusuf

    2018-05-01

    This paper deals with in silico evaluation of newly proposed heterocyclic derivatives in search of potential anticancer activity. Best possible drug candidates have been proposed using a rational approach employing a pipeline of computational techniques namely MetaPrint2D prediction, molinspiration, cheminformatics, Osiris Data warrior, AutoDock and iGEMDOCK. Lazar toxicity prediction, AdmetSAR predictions, and targeted docking studies were also performed. 27 heterocyclic derivatives were selected for bioactivity prediction and drug likeness score on the basis of Lipinski's rule, Viber rule, Ghose filter, leadlikeness and Pan Assay Interference Compounds (PAINS) rule. Bufuralol, Sunitinib, and Doxorubicin were selected as reference standard drug for the comparison of molecular descriptors and docking. Bufuralol is a known non-selective adreno-receptor blocking agent. Studies showed that beta blockers are also used against different types of cancers. Sunitinib is well known Food and Drug administration (FDA) approved pyrrole containing tyrosine kinase inhibitor and our proposed molecules possess similarities with both drug and doxorubicin is another moiety having anticancer activity. All heterocyclic derivatives were found to obey the drug filters except standard drug Doxorubicin. Bioactivity score of the compounds was predicted for drug targets including enzymes, nuclear receptors, kinase inhibitors, G protein-coupled receptor (GPCR) ligands and ion channel modulators. Absorption, distribution, metabolism and toxicity (ADMET) prediction of all proposed compound showed good Blood-brain barrier (BBB) penetration, Human intestinal absorption (HIA), Caco-2 cell permeability except compound-11 and was found to have no AdmetSAR toxicity as well as carcinogenic effect. Compounds 1-9 were slightly mutagenic while compound 2, 11, 20 and 21 showed carcinogenic effect according to Lazar toxicity prediction. Rests of the compounds were predicted to have no side effect

  7. Medication possession ratio predicts antiretroviral regimens persistence in Peru.

    Science.gov (United States)

    Salinas, Jorge L; Alave, Jorge L; Westfall, Andrew O; Paz, Jorge; Moran, Fiorella; Carbajal-Gonzalez, Danny; Callacondo, David; Avalos, Odalie; Rodriguez, Martin; Gotuzzo, Eduardo; Echevarria, Juan; Willig, James H

    2013-01-01

    In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

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

    Directory of Open Access Journals (Sweden)

    Donald Emilio Kalonio

    2017-12-01

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

  9. Isolation and identification of flavonoids from anticancer and ...

    African Journals Online (AJOL)

    Isolation and identification of flavonoids from anticancer and neuroprotective extracts of Trigonella foenum graecum. Shabina Ishtiaq Ahmed, Muhammad Qasim Hayat, Saadia Zahid, Muhammad Tahir, Qaisar Mansoor, Muhammad Ismail, Kristen Keck, Robert Bates ...

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

    African Journals Online (AJOL)

    SAM

    2014-05-21

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

  11. Supramolecular "Trojan Horse" for Nuclear Delivery of Dual Anticancer Drugs.

    Science.gov (United States)

    Cai, Yanbin; Shen, Haosheng; Zhan, Jie; Lin, Mingliang; Dai, Liuhan; Ren, Chunhua; Shi, Yang; Liu, Jianfeng; Gao, Jie; Yang, Zhimou

    2017-03-01

    Nuclear delivery and accumulation are very important for many anticancer drugs that interact with DNA or its associated enzymes in the nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the coassembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin. The resulting nanomaterials behave as the "Trojan Horse" that transported soldiers (anticancer drugs) across the walls of the castle (cell and nucleus membranes). Therefore, they show improved inhibition capacity to cancer cells including the drug resistant cancer cell and promote the synergistic tumor suppression property in vivo. We envision that our strategy of constructing nanomaterials by metal chelation would offer new opportunities to develop nanomedicines for combination chemotherapy.

  12. Screening of potent anticancer drug taxol from Entophytic fungus ...

    African Journals Online (AJOL)

    Muthumary

    2011-02-21

    Feb 21, 2011 ... Isolation and detection of taxol, an anticancer drug produced from ... cancer cell line, taxol produced by the test fungus in MID culture medium was isolated for its .... then plotted on a graph. RESULTS AND ... Wavelength (nm).

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

    Indian Academy of Sciences (India)

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

  14. Anticancer Effect of AntiMalarial Artemisinin Compounds

    African Journals Online (AJOL)

    Artemisinin is a naturally occurring antimalarial showing anticancer properties. ..... Artemisinins usually promote apoptosis rather than necrosis in most cases ... artemisinin-mediated inhibition of vascular endothelial growth factor C (VEGF-C).

  15. NSAIDs: Old Drugs Reveal New Anticancer Targets

    Directory of Open Access Journals (Sweden)

    Gary A. Piazza

    2010-05-01

    Full Text Available There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly, certain derivatives that were synthesized based on in silico modeling displayed increased potency to inhibit tumor cell growth. Other experiments have shown that sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP levels and that this activity is closely associated with its ability to selectively induce apoptosis of tumor cells. Together, these studies suggest that COX-independent mechanisms can be targeted to develop safer and more efficacious drugs for cancer chemoprevention.

  16. Anticancer Vitamin K3 Analogs: A Review.

    Science.gov (United States)

    Badave, Kirti D; Khan, Ayesha A; Rane, Sandhya Y

    2016-01-01

    Menadione (Vitamin K3) comprises of 1,4-naphthoquinone (NQ) moiety that can form redox isomers such as napthosemiquinone (NSQ) and catechol by accepting one or two electrons, respectively. The quinone redox cycling ability leads to the generation of "reactive oxygen species" (ROS) as well as arylation reactions, which are of biological relevance. This ability can be modulated with the help of suitable derivatization. A pharmacophore can be appended at suitable position of Vitamin K3 to have a synergistic or additive effect. In the present review, an attempt has been made to accrue such derivatives modified at 1 or 2 position and evaluated for their cytotoxicity activity on different series of human cancer cell lines such as HeLa, HL-60 and MCF- 7 etc. Production of reactive oxygen species (ROS) and mitochondrial dysfunction caused by Vitamin K3 derivatives leads to apoptosis and tumor inhibition. Recently, the CR-108 compound has shown to exhibit oxidative path together with non-oxidative phosphorylation of p38 MAP kinase in human breast cancer cells. Thus the chemical-biological interactions have been discussed which can be further extrapolated for the development of a potent anticancer drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. MECHANOMAGNETIC REACTOR FOR ACTIVATION OF ANTICANCER DRUGS

    Directory of Open Access Journals (Sweden)

    Orel V. E.

    2014-02-01

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

  18. PP2A-Mediated Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Weibo Chen

    2013-01-01

    Full Text Available PP2A is a family of mammalian serine/threonine phosphatases that is involved in the control of many cellular functions including protein synthesis, cellular signaling, cell cycle determination, apoptosis, metabolism, and stress responses through the negative regulation of signaling pathways initiated by protein kinases. Rapid progress is being made in the understanding of PP2A complex and its functions. Emerging studies have correlated changes in PP2A with human diseases, especially cancer. PP2A is comprised of 3 subunits: a catalytic subunit, a scaffolding subunit, and a regulatory subunit. The alternations of the subunits have been shown to be in association with many human malignancies. Therapeutic agents targeting PP2A inhibitors or activating PP2A directly have shed light on the therapy of cancers. This review focuses on PP2A structure, cancer-associated mutations, and the targeting of PP2A-related molecules to restore or reactivate PP2A in anticancer therapy, especially in digestive system cancer therapy.

  19. Potential Anticancer Properties of Grape Antioxidants

    Directory of Open Access Journals (Sweden)

    Kequan Zhou

    2012-01-01

    Full Text Available Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera, one of the world’s largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted.

  20. In vitro anticancer properties of selected Eucalyptus species.

    Science.gov (United States)

    Bhuyan, Deep Jyoti; Sakoff, Jennette; Bond, Danielle R; Predebon, Melanie; Vuong, Quan V; Chalmers, Anita C; van Altena, Ian A; Bowyer, Michael C; Scarlett, Christopher J

    2017-08-01

    In spite of the recent advancements in oncology, the overall survival rate for pancreatic cancer has not improved over the last five decades. Eucalypts have been linked with cytotoxic and anticancer properties in various studies; however, there is very little scientific evidence that supports the direct role of eucalypts in the treatment of pancreatic cancer. This study assessed the anticancer properties of aqueous and ethanolic extracts of four Eucalyptus species using an MTT assay. The most promising extracts were further evaluated using a CCK-8 assay. Apoptotic studies were performed using a caspase 3/7 assay in MIA PaCa-2 cells. The aqueous extract of Eucalyptus microcorys leaf and the ethanolic extract of Eucalyptus microcorys fruit inhibited the growth of glioblastoma, neuroblastoma, lung and pancreatic cancer cells by more than 80% at 100 μg/mL. The E. microcorys and Eucalyptus saligna extracts showed lower GI 50 values than the ethanolic Eucalyptus robusta extract in MIA PaCa-2 cells. Aqueous E. microcorys leaf and fruit extracts at 100 μg/mL exerted significantly higher cell growth inhibition in MIA PaCa-2 cells than other extracts (p  0.05) were observed in aqueous E. microcorys leaf (86.05 ± 4.75 μg/mL) and fruit (64.66 ± 15.97 μg/mL) and ethanolic E. microcorys leaf (79.30 ± 29.45 μg/mL) extracts in MIA PaCa-2 cells using the CCK-8 assay. Caspase 3/7-mediated apoptosis and morphological changes of cells were also witnessed in MIA PaCa-2 cells after 24 h of treatment with the extracts. This study highlighted the significance of E. microcorys as an important source of phytochemicals with efficacy against pancreatic cancer cells. Further studies are warranted to purify and structurally identify individual compounds and elucidate their mechanisms of action for the development of more potent and specific chemotherapeutic agents for pancreatic cancer.

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

    Directory of Open Access Journals (Sweden)

    Yiming Xu

    2017-11-01

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

  2. When ubiquitin meets NF-κB: a trove for anti-cancer drug development.

    Science.gov (United States)

    Wu, Zhao-Hui; Shi, Yuling

    2013-01-01

    During the last two decades, the studies on ubiquitination in regulating transcription factor NF-κB activation have elucidated the expanding role of ubiquitination in modulating cellular events by non-proteolytic mechanisms, as well as by proteasomal degradation. The significance of ubiquitination has also been recognized in regulating gene transcription, epigenetic modifications, kinase activation, DNA repair and subcellular translocation. This progress has been translated into novel strategies for developing anti-cancer therapeutics, exemplified by the success of the first FDA-approved proteasome inhibitor drug Bortezomib. Here we discuss the current understanding of the ubiquitin-proteasome system and how it is involved in regulating NF-κB signaling pathways in response to a variety of stimuli. We also focus on the recent progress of anti-cancer drug development targeting various steps of ubiquitination process, and the potential of these drugs in cancer treatment as related to their impact on NF-κB activation.

  3. Anticancer Chemodiversity of Ranunculaceae Medicinal Plants: Molecular Mechanisms and Functions.

    Science.gov (United States)

    Hao, Da-Cheng; He, Chun-Nian; Shen, Jie; Xiao, Pei-Gen

    2017-02-01

    The buttercup family, Ranunculaceae, comprising more than 2,200 species in at least 62 genera, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine since the beginning of human civilization. Various medicinal phytometabolites have been found in Ranunculaceae plants, many of which, such as alkaloids, terpenoids, saponins, and polysaccharides, have shown anti-cancer activities in vitro and in vivo. Most concerns have been raised for two epiphany molecules, the monoterpene thymoquinone and the isoquinoline alkaloid berberine. At least 17 genera have been enriched with anti-cancer phytometabolites. Some Ranunculaceae phytometabolites induce the cell cycle arrest and apoptosis of cancer cells or enhance immune activities, while others inhibit the proliferation, invasion, angiogenesis, and metastasis, or reverse the multi-drug resistance of cancer cells thereby regulating all known hallmarks of cancer. These phytometabolites could exert their anti-cancer activities via multiple signaling pathways. In addition, absorption, distribution, metabolism, and excretion/toxicity properties and structure/activity relationships of some phytometabolites have been revealed assisting in the early drug discovery and development pipelines. However, a comprehensive review of the molecular mechanisms and functions of Ranunculaceae anti-cancer phytometabolites is lacking. Here, we summarize the recent progress of the anti-cancer chemo- and pharmacological diversity of Ranunculaceae medicinal plants, focusing on the emerging molecular machineries and functions of anti-cancer phytometabolites. Gene expression profiling and relevant omics platforms (e.g. genomics, transcriptomics, proteomics, and metabolomics) could reveal differential effects of phytometabolites on the phenotypically heterogeneous cancer cells.

  4. An upper and lower bound of the Medication Possession Ratio

    Directory of Open Access Journals (Sweden)

    Sperber CM

    2017-08-01

    Full Text Available Christian M Sperber, Suren R Samarasinghe, Grace P Lomax Patient Connect Limited, Guildford, UK Background: The Medication Possession Ratio (MPR is a ubiquitous and central measurement for adherence in the health care industry. However, attempts to standardize its calculation have failed, possibly due to the opacity of a single, static MPR, incapability of directly lending itself to a variety of studies, and challenges of comparing the value across studies. This work shows that the MPR strictly depends on the length of the time interval over which it is measured as well as on the dominant dispense quantity for short time intervals. Furthermore, removing a proportion of the patient cohort based on the number of acquisitions may also have a severe impact on the MPR. Therefore, it is suggested that the MPR is represented as a trend over a range of time intervals. To this end, an upper and lower bound of the MPR trend is developed with an upper bound acknowledging patients who change their treatment and the lower bound acknowledging patients who discontinue their treatment.Purpose: Introducing a representation of the MPR value as a trend rather than a static number by developing a quantitative description of an upper and lower bound of the MPR trend, while shedding light on the impacts on prefiltering the patient cohort.Patients and methods: Anonymized patient-level data was utilized as an example for a suggested calculation of an upper and lower bound of the MPR.Results: Representation of the MPR for a predefined time interval precludes a reliable MPR assessment. A quantitative approach is suggested to generate an upper and lower trend of the MPR while emphasizing the impact on removing patients with a limited number of acquisitions.Conclusion: An upper and lower trend makes the MPR more transparent and allows a better comparison across different studies. Removing patients with a limited number of acquisitions should be avoided. Keywords: MPR

  5. Biodegradable polymers for targeted delivery of anti-cancer drugs.

    Science.gov (United States)

    Doppalapudi, Sindhu; Jain, Anjali; Domb, Abraham J; Khan, Wahid

    2016-06-01

    Biodegradable polymers have been used for more than three decades in cancer treatment and have received increased interest in recent years. A range of biodegradable polymeric drug delivery systems designed for localized and systemic administration of therapeutic agents as well as tumor-targeting macromolecules has entered into the clinical phase of development, indicating the significance of biodegradable polymers in cancer therapy. This review elaborates upon applications of biodegradable polymers in the delivery and targeting of anti-cancer agents. Design of various drug delivery systems based on biodegradable polymers has been described. Moreover, the indication of polymers in the targeted delivery of chemotherapeutic drugs via passive, active targeting, and localized drug delivery are also covered. Biodegradable polymer-based drug delivery systems have the potential to deliver the payload to the target and can enhance drug availability at desired sites. Systemic toxicity and serious side effects observed with conventional cancer therapeutics can be significantly reduced with targeted polymeric systems. Still, there are many challenges that need to be met with respect to the degradation kinetics of the system, diffusion of drug payload within solid tumors, targeting tumoral tissue and tumor heterogeneity.

  6. Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Yoo, Young-Choon [Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Hwang, Young-Jeong [Division of Food Science, International University of Korea, Jinju 660-759 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-{alpha} and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX (P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

  7. Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

    International Nuclear Information System (INIS)

    Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il; Yoo, Young-Choon; Byun, Myung-Woo; Hwang, Young-Jeong; Lee, Ju-Woon

    2009-01-01

    Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-α and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX (P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

  8. Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

    Science.gov (United States)

    Mocellin, Simone; Nitti, Donato

    2008-05-01

    Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. Proteomic and metallomic strategies for understanding the mode of action of anticancer metallodrugs.

    Science.gov (United States)

    Gabbiani, Chiara; Magherini, Francesca; Modesti, Alessandra; Messori, Luigi

    2010-05-01

    Since the discovery of cisplatin and its introduction in the clinics, metal compounds have been intensely investigated in view of their possible application in cancer therapy. In this frame, a deeper understanding of their mode of action, still rather obscure, might turn crucial for the design and the obtainment of new and better anticancer agents. Due to the extreme complexity of the biological systems, it is now widely accepted that innovative and information-rich methods are absolutely needed to afford such a goal. Recently, both proteomic and metallomic strategies were successfully implemented for the elucidation of specific mechanistic features of anticancer metallodrugs within an innovative "Systems Biology" perspective. Particular attention was paid to the following issues: i) proteomic studies of the molecular basis of platinum resistance; ii) proteomic analysis of cellular responses to cytotoxic metallodrugs; iii) metallomic studies of the transformation and fate of metallodrugs in cellular systems. Notably, those pioneering studies, that are reviewed here, allowed a significant progress in the understanding of the molecular mechanisms of metal based drugs at the cellular level. A further extension of those studies and a closer integration of proteomic and metallomic strategies and technologies might realistically lead to rapid and significant advancements in the mechanistic knowledge of anticancer metallodrugs.

  11. Are symptoms of spirit possessed patients covered by the DSM-IV or DSM-5 criteria for possession trance disorder? A mixed-method explorative study in Uganda

    NARCIS (Netherlands)

    van Duijl, M.; Kleyn, W.; de Jong, J.

    2013-01-01

    Introduction and aims As in many cultures, spirit possession is a common idiom of distress in Uganda. The DSM-IV contains experimental research criteria for dissociative and possession trance disorder (DTD and PTD), which are under review for the DSM-5. In the current proposed categories of the

  12. The Secret Prover : Proving Possession of Arbitrary Files While not Giving Them Away

    NARCIS (Netherlands)

    Teepe, Wouter

    2005-01-01

    The Secret Prover is a Java application which allows a user (A) to prove to another user (B), that A possesses a file. If B also possesses this file B will get convinced, and if B does not possess this file B will gain no information on (the contents of) this file. This is the first implementation

  13. Clopidogrel in a combined therapy with anticancer drugs-effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models.

    Directory of Open Access Journals (Sweden)

    Agnieszka Denslow

    Full Text Available Clopidogrel, a thienopyridine derivative with antiplatelet activity, is widely prescribed for patients with cardiovascular diseases. In addition to antiplatelet activity, antiplatelet agents possess anticancer and antimetastatic properties. Contrary to this, results of some studies have suggested that the use of clopidogrel and other thienopyridines accelerates the progression of breast, colorectal, and prostate cancer. Therefore, in this study, we aimed to evaluate the efficacy of clopidogrel and various anticancer agents as a combined treatment using mouse models of breast, colorectal, and prostate cancer. Metastatic dissemination, selected parameters of platelet morphology and biochemistry, as well as angiogenesis were assessed. In addition, body weight, blood morphology, and biochemistry were evaluated to test toxicity of the studied compounds. According to the results, clopidogrel increased antitumor and/or antimetastatic activity of chemotherapeutics such as 5-fluorouracil, cyclophosphamide, and mitoxantrone, whereas it decreased the anticancer activity of doxorubicin, cisplatin, and tamoxifen. The mechanisms of such divergent activities may be based on the modulation of tumor vasculature via factors, such as transforming growth factor β1 released from platelets. Moreover, clopidogrel increased the toxicity of docetaxel and protected against mitoxantrone-induced toxicity, which may be due to the modulation of hepatic enzymes and protection of the vasculature, respectively. These results demonstrate that antiplatelet agents can be useful but also dangerous in anticancer treatment and therefore use of thienopyridines in patients undergoing chemotherapy should be carefully evaluated.

  14. Use of proteasome inhibitors in anticancer therapy

    Directory of Open Access Journals (Sweden)

    Sara M. Schmitt

    2011-10-01

    Full Text Available The importance of the ubiquitin-proteasome pathway to cellular function has brought it to the forefront in the search for new anticancer therapies. The ubiquitin-proteasome pathway has proven promising in targeting various human cancers. The approval of the proteasome inhibitor bortezomib for clinical treatment of relapsed/refractory multiple myeloma and mantle cell lymphoma has validated the ubiquitin-proteasome as a rational target. Bortezomib has shown positive results in clinical use but some toxicity and side effects, as well as resistance, have been observed, indicating that further development of novel, less toxic drugs is necessary. Because less toxic drugs are necessary and drug development can be expensive and time-consuming, using existing drugs that can target the ubiquitin-proteasome pathway in new applications, such as cancer therapy, may be effective in expediting the regulatory process and bringing new drugs to the clinic. Toward this goal, previously approved drugs, such as disulfiram, as well as natural compounds found in common foods, such as green tea polyphenol (--EGCG and the flavonoid apigenin, have been investigated for their possible proteasome inhibitory and cell death inducing abilities. These compounds proved quite promising in preclinical studies and have now moved into clinical trials, with preliminary results that are encouraging. In addition to targeting the catalytic activity of the proteasome pathway, upstream regulators, such as the 19S regulatory cap, as well as E1, E2, and E3, are now being investigated as potential drug targets. This review outlines the development of novel proteasome inhibitors from preclinical to clinical studies, highlighting their abilities to inhibit the tumor proteasome and induce apoptosis in several human cancers.

  15. Burdens and Standards of Proof in Possession of Unexplained ...

    African Journals Online (AJOL)

    Worku_Y

    However, society does not want to attain such goals at any cost. .... elements).7 The prosecutor must prove at least the following four threshold .... not significantly contribute to the effective enforcement of the criminal law .... France and the.

  16. Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

    Science.gov (United States)

    Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

    2015-04-10

    Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Readability Comparison of Pro- and Anti-Cancer Screening Online Messages in Japan

    Science.gov (United States)

    Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masahumi; Kato, Mio; Kiuchi, Takahiro

    2016-01-01

    Background: Cancer screening rates are lower in Japan than those in western countries. Health professionals publish pro-cancer screening messages on the internet to encourage audiences to undergo cancer screening. However, the information provided is often difficult to read for lay persons. Further, anti-cancer screening activists warn against cancer screening with messages on the Internet. We aimed to assess and compare the readability of pro- and anti-cancer screening online messages in Japan using a measure of readability. Methods: We conducted web searches at the beginning of September 2016 using two major Japanese search engines (Google.jp and Yahoo!.jp). The included websites were classified as “anti”, “pro”, or “neutral” depending on the claims, and “health professional” or “non-health professional” depending on the writers. Readability was determined using a validated measure of Japanese readability. Statistical analysis was conducted using two-way ANOVA. Results: In the total 159 websites analyzed, anti-cancer screening online messages were generally easier to read than pro-cancer screening online messages, Messages written by health professionals were more difficult to read than those written by non-health professionals. Claim × writer interaction was not significant. Conclusion: When health professionals prepare pro-cancer screening materials for publication online, we recommend they check for readability using readability assessment tools and improve text for easy comprehension when necessary. PMID:28125867

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

    Science.gov (United States)

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

    2016-07-01

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

  19. Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted Leukemia Model

    Directory of Open Access Journals (Sweden)

    Jae Gwang Park

    2017-01-01

    Full Text Available Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm-EE and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a C. militaris-administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3β (p-GSK3β and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3β-related caspase-3-dependent apoptosis.

  20. Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo.

    Science.gov (United States)

    Xiang, Jianfeng; Xiang, Yanjie; Lin, Shengming; Xin, Dongwei; Liu, Xiaoyu; Weng, Lingling; Chen, Tao; Zhang, Minguang

    2014-04-01

    Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world whose chemoprevention became increasingly important in HCC treatment. Although the anticancer effects of asparagus constituents have been investigated in several cancers, its effects on hepatocellular carcinoma have not been fully studied. In this study, we investigated the anticancer effects of the deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells using the in vitro and in vivo experimental model. Our data showed that deproteinized asparagus polysaccharide might act as an effective inhibitor on cell growth in vitro and in vivo and exert potent selective cytotoxicity against human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that it could potently induce cell apoptosis and G2/M cell cycle arrest in the more sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus polysaccharide potentiated the effects of mitomycin both in vitro and in vivo. Mechanistic studies revealed that deproteinized asparagus polysaccharide might exert its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus polysaccharide exhibited significant anticancer activity against hepatocellular carcinoma cells and could sensitize the tumoricidal effects of mitomycin, indicating that it is a potential therapeutic agent (or chemosensitizer) for liver cancer therapy.

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

    Science.gov (United States)

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

    2014-04-22

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

  2. Human synthetic lethal inference as potential anti-cancer target gene detection

    Directory of Open Access Journals (Sweden)

    Solé Ricard V

    2009-12-01

    Full Text Available Abstract Background Two genes are called synthetic lethal (SL if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases as well as on existent approved drugs (DrugBank database supports our selection of cancer-therapy candidates. Conclusions Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.

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

    Directory of Open Access Journals (Sweden)

    Krisada Sakchaisri

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

  4. Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Juan Zhang

    2018-06-01

    Full Text Available The use of photodynamic therapy (PDT and development of novel photosensitizers (PSs for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted.

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

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    Josinete B. Vieira

    2014-07-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

  7. Anti-cancer effect of HIV-1 viral protein R on doxorubicin resistant neuroblastoma.

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    Richard Y Zhao

    Full Text Available Several unique biological features of HIV-1 Vpr make it a potentially powerful agent for anti-cancer therapy. First, Vpr inhibits cell proliferation by induction of cell cycle G2 arrest. Second, it induces apoptosis through multiple mechanisms, which could be significant as it may be able to overcome apoptotic resistance exhibited by many cancerous cells, and, finally, Vpr selectively kills fast growing cells in a p53-independent manner. To demonstrate the potential utility of Vpr as an anti-cancer agent, we carried out proof-of-concept studies in vitro and in vivo. Results of our preliminary studies demonstrated that Vpr induces cell cycle G2 arrest and apoptosis in a variety of cancer types. Moreover, the same Vpr effects could also be detected in some cancer cells that are resistant to anti-cancer drugs such as doxorubicin (DOX. To further illustrate the potential value of Vpr in tumor growth inhibition, we adopted a DOX-resistant neuroblastoma model by injecting SK-N-SH cells into C57BL/6N and C57BL/6J-scid/scid mice. We hypothesized that Vpr is able to block cell proliferation and induce apoptosis regardless of the drug resistance status of the tumors. Indeed, production of Vpr via adenoviral delivery to neuroblastoma cells caused G2 arrest and apoptosis in both drug naïve and DOX-resistant cells. In addition, pre-infection or intratumoral injection of vpr-expressing adenoviral particles into neuroblastoma tumors in SCID mice markedly inhibited tumor growth. Therefore, Vpr could possibly be used as a supplemental viral therapeutic agent for selective inhibition of tumor growth in anti-cancer therapy especially when other therapies stop working.

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

    Science.gov (United States)

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

    2017-06-01

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

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

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    Hafidh Rand R

    2012-11-01

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

  10. Marijuana extracts possess the effects like the endocrine disrupting chemicals

    International Nuclear Information System (INIS)

    Watanabe, Kazuhito; Motoya, Erina; Matsuzawa, Naoki; Funahashi, Tatsuya; Kimura, Toshiyuki; Matsunaga, Tamihide; Arizono, Koji; Yamamoto, Ikuo

    2005-01-01

    The progesterone 17α-hydroxylase activity, which is one of the steroidogenic enzymes in rat testis microsomes, was significantly inhibited by crude marijuana extracts from Δ 9 -tetrahydrocannabinolic acid (THCA)- and cannabidiolic acid (CBDA)-strains. Δ 9 -Tetrahydrocannabinol, cannabidiol and cannabinol also inhibited the enzymatic activitiy with relatively higher concentration (100-1000 μM). Testosterone 6β- and 16α-hydroxylase activities together with androstenedione formation from testosterone in rat liver microsomes were also significantly inhibited by the crude marijuana extracts and the cannabinoids. Crude marijuana extracts (1 and 10 μg/ml) of THCA strain stimulated the proliferation of MCF-7 cells, although the purified cannabinoids (THC, CBD and CBN) did not show significant effects, such as the extract at the concentration of 0.01-1000 nM. These results indicate that there are some metabolic interactions between cannabinoid and steroid metabolism and that the constituents showing estrogen-like activity exist in marijuana

  11. Synthesis and biological evaluation of new C-12(α/β)-(N-) sulfamoyl-phenylamino-14-deoxy-andrographolide derivatives as potent anti-cancer agents.

    Science.gov (United States)

    Kandanur, Sai Giridhar Sarma; Nanduri, Srinivas; Golakoti, Nageswara Rao

    2017-07-01

    Andrographolide, the major diterpenoidal constituent of Andrographis paniculata (Acanthaceae) and its derivatives have been reported to possess plethora of biological properties including potent anti-cancer activity. In this work, synthesis and in-vitro anti-cancer evaluation of new C-12-substituted aryl amino 14-deoxy-andrographolide derivatives (III a-f) are reported. The substitutions include various sulfonamide moieties -SO 2 -NH-R 1 . The new derivatives (III a-e) exhibited improved cytotoxicity (GI 50 , TGI and LC 50 ) compared to andrographolide (I) and the corresponding 3,14,19-O-triacetyl andrographolide (II) when evaluated against 60 NCI cell line panel. Compounds III c and III e are found to be non-toxic to normal human dermal fibroblasts (NHDF) cells compared to reference drug THZ-1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Anticancer and cytotoxic compounds from seashells of the Persian Gulf

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    Iraj Nabipour

    2009-12-01

    Full Text Available Background: Pre-clinical studies for isolation and purification of marine compounds continued at an active pace since the last decade. Today, more than 60% of the anticancer drugs commercially available are of naturally origin thus the sea is a very favorable bed for the discovery of novel anticancer agents. Methods: A total of known 611 seashells species in the Persian Gulf were investigated for synonymy in OBIS database. Then, all the species, including their synonymy were searched in PubMed databse to find their isolated bioactive agents. Results: From 611 known seashells in the Persian Gulf, 172 genera/species had bioactive compounds. Anticancer agents were isolated and purified for 8 genera. These compounds had various structures they were polypeptide, polysaccharide, glycoprotein, alkaloid, cerebroside, and cembranoid which had different mechanism of actions including induction of apoptosis, destroying the skeletal structures of the cells, immune bioactivity and inhibition of topoisomerase I. Spisulosine is the only anticancer agent which is currently under clinical trial. Conclusions: Although, the known seashells from the Persian Gulf have potential anticancer and cytotoxic compounds but a very few investigations had been reported. Further investigations for isolation and purification on bioactive compounds from seashells of the Persian Gulf is recommended.

  13. Anticancer effects of Ganoderma lucidum: a review of scientific evidence.

    Science.gov (United States)

    Yuen, John W M; Gohel, Mayur Danny I

    2005-01-01

    "Lingzhi" (Ganoderma lucidum), a popular medicinal mushroom, has been used in China for longevity and health promotion since ancient times. Investigations into the anticancer activity of lingzhi have been performed in both in vitro and in vivo studies, supporting its application for cancer treatment and prevention. The proposed anticancer activity of lingzhi has prompted its usage by cancer patients. It remains debatable as to whether lingzhi is a food supplement for health maintenance or actually a therapeutic "drug" for medical proposes. Thus far there has been no report of human trials using lingzhi as a direct anticancer agent, despite some evidence showing the usage of lingzhi as a potential supplement to cancer patients. Cellular immune responses and mitogenic reactivity of cancer patients have been enhanced by lingzhi, as reported in two randomized and one nonrandomized trials, and the quality of life of 65% of lung cancer patients improved in one study. The direct cytotoxic and anti-angiogenesis mechanisms of lingzhi have been established by in vitro studies; however, clinical studies should not be neglected to define the applicable dosage in vivo. At present, lingzhi is a health food supplement to support cancer patients, yet the evidence supporting the potential of direct in vivo anticancer effects should not be underestimated. Lingzhi or its products can be classified as an anticancer agent when current and more direct scientific evidence becomes available.

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

    Science.gov (United States)

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

    2012-01-01

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

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

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    Sung-Suk Suh

    2017-08-01

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

  16. Investigation of anticancer potential of hypophyllanthin and phyllanthin against breast cancer by in vitro and in vivo methods

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    Madhukiran Parvathaneni

    2014-02-01

    Full Text Available Objective: To investigate the in vitro and in vivo anticancer activities of hypophyllanthin and phyllanthin isolated from Phyllanthus amarus Schum & Thonn against breast cancer. Methods: In vitro anticancer activity was evaluated against two cell lines (MCF-7 and MDAMB-231 using MTT assay. In vivo anticancer activity was tested using Sprague-Dawley rats with N-methyl-N-nitrosourea induced mammary cancer. Results: In vitro studies demonstrated a dose-dependent inhibitory effect on cell growth with IC50 values of (35.18依1.48 µg/mL (hypophyllanthin and (32.51依0.95 µg/mL (phyllanthin for MCF-7; (38.74 依1.24 (hypophyllanthin and (32.2依1.17 (phyllanthin for MDA-MB-231 breast cancer cell lines. Tumor weights per group at doses of 5 and 10 mg/kg/day for hypophyllanthin (12.82 and 12.06 g and phyllanthin (11.95 and 8.87 g treated groups were significantly (P<0.001 lower than untreated N-methyl-N-nitrosourea group (35.85. Conclusions: Results of the present research work indicated that the isolated lignan compounds, hypophyllanthin and phyllanthin showed significant anticancer activities against breast cancer, in vitro and in vivo.

  17. Nanoformulation for anticancer drug delivery: Enhanced pharmacokinetics and circulation

    Science.gov (United States)

    Parekh, Gaurav

    In this study, we have explored the application of the Layer-by-Layer (LbL) assembly technique for improving injectable drug delivery systems of low soluble anticancer drugs (e.g. Camptothecin (CPT), Paclitaxel (PTX) or Doxorubicin (DOX)). For this study, a polyelectrolyte shell encapsulates different types of drug nanocores (e.g. soft core, nanomicelle or solid lipid nanocores).The low soluble drugs tend to crystallize and precipitate in an aqueous medium. This is the reason they cannot be injected and may have low concentrations and low circulation time in the blood. Even though these drugs when present in the cancer microenvironment have high anti-tumor inhibition, the delivery to the tumor site after intravenous administration is a challenge. We have used FDA-approved biopolymers for the process and elaborated formation of 60-90 nm diameter initial cores, which was stabilized by multilayer LbL shells for controlled release and longer circulation. A washless LbL assembly process was applied as an essential advancement in nano-assembly technology using low density nanocore (lipids) and preventing aggregation. This advancement reduced the number of process steps, enhanced drug loading capacity, and prevented the loss of expensive polyelectrolytes. Finally, we elaborated a general nano-encapsulation process, which allowed these three important anticancer drug core-shell nanocapsules with diameters of ca. 100-130 nm (this small size is a record for LbL encapsulation technique) to be stable in the serum and the blood for at least one week, efficient for cancer cell culture studies, injectable to mice with circulation for 4 hrs, and effective in suppressing tumors. This work is divided into three studies. The first study (CHAPTER 4) explores the application of LbL assembly for encapsulating a soft core of albumin protein and CPT anticancer drug. In order to preserve the activity of drug in the core, a unique technique of pH reversal is employed where the first few

  18. Targeting apoptotic machinery as approach for anticancer therapy: Smac mimetics as anticancer agents

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    Nevine M.Y. Elsayed

    2015-06-01

    Full Text Available Apoptosis is a chief regulator of cellular homeostasis. Impairment of apoptotic machinery is a main characteristic of several diseases such as cancer, where the evasion of apoptosis is a cardinal hallmark of cancer. Apoptosis is regulated by contribution of pro- and anti- apoptotic proteins, where caspases are the main executioners of the apoptotic machinery. IAP (inhibitors of apoptosis proteins is a family of endogenous inhibitors of apoptosis, which perform their function through interference with the function of caspases. Smac (second mitochondria-derived activator of caspases is endogenous inhibitor of IAPs, thus it is one of the major proapoptotic endogenous proteins. Thus, the development of Smac mimetics has evolved as an approach for anticancer therapy. Several Smac mimetic agents have been introduced to clinical trial such as birinapanet 12. Herein, the history of development of Smac mimetics along with the recent development in this field is briefly discussed.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-15

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

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

    International Nuclear Information System (INIS)

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

    2009-07-01

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

  1. Effect of playing tactics on achieving score-box possessions in a random series of team possessions from Norwegian professional soccer matches.

    Science.gov (United States)

    Tenga, Albin; Holme, Ingar; Ronglan, Lars Tore; Bahr, Roald

    2010-02-01

    Methods of analysis that include an assessment of opponent interactions are thought to provide a more valid means of team match performance. The purpose of this study was to examine the effect of playing tactics on achieving score-box possession by assessing opponent interactions in Norwegian elite soccer matches. We analysed a random series of 1703 team possessions from 163 of 182 (90%) matches played in the professional men's league during the 2004 season. Multidimensional qualitative data obtained from ten ordered categorical variables were used. Offensive tactics were more effective in producing score-box possessions when playing against an imbalanced defence (28.5%) than against a balanced defence (6.5%) (P tactics on producing score-box possessions, and improves the validity of team match-performance analysis in soccer.

  2. Alkaloids as Cyclooxygenase Inhibitors in Anticancer Drug Discovery.

    Science.gov (United States)

    Hashmi, Muhammad Ali; Khan, Afsar; Farooq, Umar; Khan, Sehroon

    2018-01-01

    Cancer is the leading cause of death worldwide and anticancer drug discovery is a very hot area of research at present. There are various factors which control and affect cancer, out of which enzymes like cyclooxygenase-2 (COX-2) play a vital role in the growth of tumor cells. Inhibition of this enzyme is a very useful target for the prevention of various types of cancers. Alkaloids are a diverse group of naturally occurring compounds which have shown great COX-2 inhibitory activity both in vitro and in vivo. In this mini-review, we have discussed different alkaloids with COX-2 inhibitory activities and anticancer potential which may act as leads in modern anticancer drug discovery. Different classes of alkaloids including isoquinoline alkaloids, indole alkaloids, piperidine alkaloids, quinazoline alkaloids, and various miscellaneous alkaloids obtained from natural sources have been discussed in detail in this review. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Anti-cancer natural products isolated from chinese medicinal herbs

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    Wu Guosheng

    2011-07-01

    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  4. New Molecular Targets of Anticancer Therapy - Current Status and Perspectives.

    Science.gov (United States)

    Zajac, Marianna; Muszalska, Izabela; Jelinska, Anna

    2016-01-01

    Molecularly targeted anticancer therapy involves the use of drugs or other substances affecting specific molecular targets that play a part in the development, progression and spread of a given neoplasm. By contrast, the majority of classical chemotherapeutics act on all rapidly proliferating cells, both healthy and cancerous ones. Target anticancer drugs are designed to achieve a particular aim and they usually act cytostatically, not cytotoxically like classical chemotherapeutics. At present, more than 300 biological molecular targets have been identified. The proteins involved in cellular metabolism include (among others) receptor proteins, signal transduction proteins, mRNA thread matrix synthesis proteins participating in neoplastic transformation, cell cycle control proteins, functional and structural proteins. The receptor proteins that are targeted by currently used anticancer drugs comprise the epithelial growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor(VEGFR). Target anticancer drugs may affect extracellular receptor domains (antibodies) or intracellular receptor domains (tyrosine kinase inhibitors). The blocking of the mRNA thread containing information about the structure of oncogenes (signal transduction proteins) is another molecular target of anticancer drugs. That type of treatment, referred to as antisense therapy, is in clinical trials. When the synthesis of genetic material is disturbed, in most cases the passage to the next cycle phase is blocked. The key proteins responsible for the blockage are cyclines and cycline- dependent kinases (CDK). Clinical trials are focused on natural and synthetic substances capable of blocking various CDKs. The paper discusses the molecular targets and chemical structure of target anticancer drugs that have been approved for and currently applied in antineoplastic therapy together with indications and contraindications for their

  5. Studies on anticancer activities of lactoferrin and lactoferricin.

    Science.gov (United States)

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

    2013-09-01

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

  6. Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives

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    Yang Li

    2016-02-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Christina Leah B. Kline

    2018-01-01

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

  9. Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available The poor bioavailability of Berberine (BBR and Betulinic acid (BA limits the development of these promising anticancer agents for clinical use. In the current study, BBR and BA in spray dried (SD mucoadhesive microparticle formulations were prepared.A patented dual channel spray gun technology established in our laboratory was used for both formulations. Gastrointestinal (GI permeability studies were carried out using Caco-2 cell monolayer grown in in-vitro system. The oral bioavailability and pharmacokinetic profile of SD formulations were studied in Sprague Dawley rats. A549 orthotopic and H1650 metastatic NSCLC models were utilized for the anticancer evaluations.Pharmacokinetic studies demonstrated that BBR and BA SD formulations resulted in 3.46 and 3.90 fold respectively, significant increase in plasma Cmax concentrations. AUC levels were increased by 6.98 and 7.41 fold in BBR and BA SD formulations, respectively. Compared to untreated controls groups, 49.8 & 53.4% decrease in the tumor volumes was observed in SD formulation groups of BBR and BA, respectively. Molecular studies done on excised tumor (A549 tissue suggested that BBR in SD form resulted in a significant decrease in the survivin, Bcl-2, cyclin D1, MMP-9, HIF-1α, VEGF and CD31 expressions. Cleaved caspase 3, p53 and TUNEL expressions were increased in SD formulations. The RT-PCR analysis on H1650 tumor tissue suggested that p38, Phospho-JNK, Bax, BAD, cleaved caspase 3&8 mRNA expressions were significantly increased in BA SD formulations. Chronic administration of BBR and BA SD formulations did not show any toxicity.Due to significant increase in oral bioavailability and superior anticancer effects, our results suggest that spray drying is a superior alternative formulation approach for oral delivery of BBR and BA.

  10. New families of conservative systems on $S^2$ possessing an integral of fourth degree in momenta

    OpenAIRE

    Selivanova, Elena N.

    1997-01-01

    There is a well-known example of integrable conservative system on $S^2$, the case of Kovalevskaya in the dynamics of a rigid body, possessing an integral of fourth degree in momenta. Goryachev proposed a one-parameter family of examples of conservative systems on $S^2$ possessing an integral of fourth degree in momenta which includes the case of Kovalevskaya. In this paper we proposed new examples of conservative systems on $S^2$ possessing an integral of fourth degree in momenta.

  11. Competencies that managers should possess - a case study at IPEN

    International Nuclear Information System (INIS)

    Gimenes, Celso Huerta; Barroso, Antonio Carlos de Oliveira; Imakuma, Kengo

    2009-01-01

    To guide human resources selection and development, organizations usually have a list of the competencies they consider crucial for the various segments of their endeavor. At IPEN, a R and D institute with graduate teaching (within USP framework) and some production facilities, the elaboration of a list of the highly appraised competencies for IPEN's managers become a research theme in itself. This work has produced: a methodology to generate, validate and recycle periodically the list and descriptions of managers' competencies; and the first version of the list. Delphi questionnaires were applied via web using 'Lime Survey', a freeware that enables import and export the data as csv files and has a simple and workable language for database access. The consistency of the numerical results, as well as the consensus preferences manifested by the sample is discussed in the paper. Also a segmentation and multivariate statistical analysis to reveal differences and similarities among the various subgroups of the sample is presented providing a lot of insightful information. The merit of structuring the pertinence of the competencies according to seven BNQA's criteria is discussed. Combining the manifested preference of the sample with a factor analysis to check the most significant loads in each construct a reduced set of competencies is proposed. This reduced set can be the base for IPEN's directors to select the crucial set of managers' competence. The methodology here explained can be used each two years to co-validate and update this reduced set. (author)

  12. Discovery of drugs that possess activity against feline leukemia virus.

    Science.gov (United States)

    Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M

    2012-04-01

    Feline leukemia virus (FeLV) is a gammaretrovirus that is a significant cause of neoplastic-related disorders affecting cats worldwide. Treatment options for FeLV are limited, associated with serious side effects, and can be cost-prohibitive. The development of drugs used to treat a related retrovirus, human immunodeficiency virus type 1 (HIV-1), has been rapid, leading to the approval of five drug classes. Although structural differences affect the susceptibility of gammaretroviruses to anti-HIV drugs, the similarities in mechanism of replication suggest that some anti-HIV-1 drugs may also inhibit FeLV. This study demonstrates the anti-FeLV activity of four drugs approved by the US FDA (Food and Drug Administration) at non-toxic concentrations. Of these, tenofovir and raltegravir are anti-HIV-1 drugs, while decitabine and gemcitabine are approved to treat myelodysplastic syndromes and pancreatic cancer, respectively, but also have anti-HIV-1 activity in cell culture. Our results indicate that these drugs may be useful for FeLV treatment and should be investigated for mechanism of action and suitability for veterinary use.

  13. A high-throughput quantitative expression analysis of cancer-related genes in human HepG2 cells in response to limonene, a potential anticancer agent.

    Science.gov (United States)

    Hafidh, Rand R; Hussein, Saba Z; MalAllah, Mohammed Q; Abdulamir, Ahmed S; Abu Bakar, Fatimah

    2017-11-14

    Citrus bioactive compounds, as active anticancer agent, have been under focus by several studies worldwide. However, the underlying genes responsible for the anticancer potential have not been sufficiently highlighted. The current study investigated the gene expression profile of hepatocellular carcinoma, HepG2, cells after treatment with Limonene. The concentration that killed 50% of HepG2 cells was used to elucidate the genetic mechanisms of limonene anticancer activity. The apoptotic induction was detected by flow cytometry and confocal fluorescence microscope. Two of pro-apoptotic events, caspase-3 activation and phosphatidylserine translocation were manifested by confocal fluorescence microscopy. High-throughput real-time PCR was used to profile 1023 cancer-related genes in 16 different gene families related to the cancer development. In comparison to untreated cells, limonene increased the percentage of apoptotic cells up to 89.61%, by flow cytometry, and 48.2% by fluorescence microscopy. There was a significant limonene-driven differential gene expression of HepG2 cells in 15 different gene families. Limonene was shown to significantly (>2log) up-regulate and down-regulate 14 and 59 genes, respectively. The affected gene families, from most to least affected, were apoptosis induction, signal transduction, cancer genes augmentation, alteration in kinases expression, inflammation, DNA damage repair, and cell cycle proteins. The current study reveals that limonene could be a promising, cheap, and effective anticancer compound. The broad spectrum of limonene anticancer activity is interesting for anticancer drug development. Further research is needed to confirm the current findings and to examine the anticancer potential of limonene along with underlying mechanisms on different cell lines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. 2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent.

    Directory of Open Access Journals (Sweden)

    Masako Yokoo

    Full Text Available 2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-β-CyD has recently been approved for the treatment of Niemann-Pick Type C disease, a lysosomal lipid storage disorder, and is used in clinical practice. Since cholesterol accumulation and/or dysregulated cholesterol metabolism has been described in various malignancies, including leukemia, we hypothesized that HP-β-CyD itself might have anticancer effects. This study provides evidence that HP-β-CyD inhibits leukemic cell proliferation at physiologically available doses. First, we identified the potency of HP-β-CyD in vitro against various leukemic cell lines derived from acute myeloid leukemia (AML, acute lymphoblastic leukemia and chronic myeloid leukemia (CML. HP-β-CyD treatment reduced intracellular cholesterol resulting in significant leukemic cell growth inhibition through G2/M cell-cycle arrest and apoptosis. Intraperitoneal injection of HP-β-CyD significantly improved survival in leukemia mouse models. Importantly, HP-β-CyD also showed anticancer effects against CML cells expressing a T315I BCR-ABL mutation (that confers resistance to most ABL tyrosine kinase inhibitors, and hypoxia-adapted CML cells that have characteristics of leukemic stem cells. In addition, colony forming ability of human primary AML and CML cells was inhibited by HP-β-CyD. Systemic administration of HP-β-CyD to mice had no significant adverse effects. These data suggest that HP-β-CyD is a promising anticancer agent regardless of disease or cellular characteristics.

  15. Caffeine induces metformin anticancer effect on fibrosarcoma in hamsters.

    Science.gov (United States)

    Popović, D J; Lalošević, D; Miljković, D; Popović, K J; Čapo, I; Popović, J K

    2018-04-01

    We investigated the effect of metformin and caffeine on fibrosarcoma in hamsters. 32 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups, with a minimum of 6 animals per group. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' back in 4 groups. The first experimental group started peroral treatment with metformin 500 mg/kg daily, the second with caffeine 100 mg/kg daily and the third with a combination of metformin 500 mg/kg and caffeine 100 mg/kg daily, via a gastric probe 3 days before tumor inoculation. After 2 weeks, when the tumors were approximately 2 cm in the control group, all animals were sacrificed. The blood was collected for glucose and other analyses. The tumors were excised and weighed and their diameters were measured. The tumor samples were pathohistologically (HE) and immunohistochemically (Ki-67, CD 31, COX IV, GLUT-1, iNOS) assessed and the main organs toxicologically analyzed, including the control animals that had received metformin and caffeine. Tumor volume was determined using the formula LxS2/2, where L was the longest and S the shortest diameter. Ki-67-positive cells in the tumor samples were quantified. Images were taken and processed by software UTHSCSA Image Tools for Windows Version 3.00. Statistical significances were determined by the Student's t-test. The combination of metformin and caffeine inhibited fibrosarcoma growth in hamsters without toxicity. Administration of metformin with caffeine might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.

  16. Listeria monocytogenes as a vector for anti-cancer therapies.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    The intracellular pathogen Listeria monocytogenes represents a promising therapeutic vector for the delivery of DNA, RNA or protein to cancer cells or to prime immune responses against tumour-specific antigens. A number of biological properties make L. monocytogenes a promising platform for development as a vector for either gene therapy or as an anti-cancer vaccine vector. L. monocytogenes is particularly efficient in mediating internalization into host cells. Once inside cells, the bacterium produces specific virulence factors which lyse the vaculolar membrane and allow escape into the cytoplasm. Once in the cytosol, L. monocytogenes is capable of actin-based motility and cell-to-cell spread without an extracellular phase. The cytoplasmic location of L. monocytogenes is significant as this potentiates entry of antigens into the MHC Class I antigen processing pathway leading to priming of specific CD8(+) T cell responses. The cytoplasmic location is also beneficial for the delivery of DNA (bactofection) by L. monocytogenes whilst cell-to-cell spread may facilitate access of the vector to cells throughout the tumour. Several preclinical studies have demonstrated the ability of L. monocytogenes for intracellular gene or protein delivery in vitro and in vivo, and this vector has also displayed safety and efficacy in clinical trial. Here, we review the features of the L. monocytogenes host-pathogen interaction that make this bacterium such an attractive candidate with which to induce appropriate therapeutic responses. We focus primarily upon work that has led to attenuation of the pathogen, demonstrated DNA, RNA or protein delivery to tumour cells as well as research that shows the efficacy of L. monocytogenes as a vector for tumour-specific vaccine delivery.

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

    African Journals Online (AJOL)

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

  18. Anticancer Drugs Targeting the Mitochondrial Electron Transport Chain

    Czech Academy of Sciences Publication Activity Database

    Rohlena, Jakub; Dong, L.-F.; Ralph, S.J.; Neužil, Jiří

    2011-01-01

    Roč. 15, č. 12 (2011), s. 2951-2974 ISSN 1523-0864 R&D Projects: GA AV ČR(CZ) KAN200520703 Institutional research plan: CEZ:AV0Z50520701 Keywords : Targets for anticancer drugs * mitochondrial electron transport chain * mitocans Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.456, year: 2011

  19. Anti-cancer and antioxidant properties of phenolics isolated from ...

    African Journals Online (AJOL)

    Purpose: To investigate the antioxidant and anticancer activities of phenolics from the leaf extract of Toona sinensis (TS). Methods: Acetone leaf extract of TS was screened for total phenolic and flavanoid contents, and the flanonoids were subjected to high performance liquid chromatographic (HPLC) analysis. Antioxidant ...

  20. Classification of mitocans, anti-cancer drugs acting on mitochondria

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Dong, L. F.; Rohlena, Jakub; Truksa, Jaroslav; Ralph, S. J.

    2013-01-01

    Roč. 13, č. 3 (2013), s. 199-208 ISSN 1567-7249 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitocans * Anti-cancer therapeutics * Classification Subject RIV: EB - Gene tics ; Molecular Biology Impact factor: 3.524, year: 2013

  1. Natural flora and anticancer regime: milestones and roadmap.

    Science.gov (United States)

    Bhatnagar, Ira; Thomas, Noel Vinay; Kim, Se-Kwon

    2013-07-01

    Cancer has long been an area of extensive research both at the molecular as well as pharmaceutical level. However, lack of understanding of the underlying molecular signalling and the probable targets of therapeutics is a major concern in successful treatment of cancer. The situation becomes even worse, with the increasing side effects of the existing synthetic commercial drugs. Natural compounds especially those derived from plants have been best explored for their anticancer properties and most of them have been efficient against the known molecular targets of cancer. However, advent of biotechnology and resulting advances in medical arena have let to the increasing knowledge of newer carcinogenic signaling agents which has made the anticancer drug discovery even more demanding. The present review aims to bring forward the molecular mediators of cancer and compiles the plant derived anticancer agents with special emphasis on their clinical status. Since marine arena has proved to be a tremendous source of pharmaceutical agents, this review also focuses on the anticancer potential of marine plants especially algae. This is a comprehensive review covering major aspects of cancer mediation and utilization of marine flora for remediation of this deadly disease.

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

    African Journals Online (AJOL)

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

  3. Synthesis and anticancer evaluation of (-1)- aretigenin derivatives

    International Nuclear Information System (INIS)

    Xu, Y.; Chen, G.

    2014-01-01

    Seven (-)-arctigenin derivatives 1-7 were designed and synthesized by using Mannich and acylation methods to improve the activity and bioavailability of (-)-arctigenin. Structures of compounds 1-7 were elucidated on the basis of spectroscopic analysis and chemical evidence. Anticancer activity of these compounds on SGC7901 was assayed in vitro. (author)

  4. Synthesis and anticancer evaluation of (-1)- aretigenin derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Y.; Chen, G. [Liaoning Univ. of Traditional Chinese Medicine, Dalian (China)

    2014-10-15

    Seven (-)-arctigenin derivatives 1-7 were designed and synthesized by using Mannich and acylation methods to improve the activity and bioavailability of (-)-arctigenin. Structures of compounds 1-7 were elucidated on the basis of spectroscopic analysis and chemical evidence. Anticancer activity of these compounds on SGC7901 was assayed in vitro. (author)

  5. Sphingolipid metabolism enzymes as targets for anticancer therapy

    NARCIS (Netherlands)

    Kok, JW; Sietsma, H

    Treatment with anti-cancer agents in most cases ultimately results in apoptotic cell death of the target tumour cells. Unfortunately, tumour cells can develop multidrug resistance, e.g., by a reduced propensity to engage in apoptosis by which they become insensitive to multiple chemotherapeutics.

  6. Classification of mitocans, anti-cancer drugs acting on mitochondria

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Dong, L. F.; Rohlena, Jakub; Truksa, Jaroslav; Ralph, S. J.

    2013-01-01

    Roč. 13, č. 3 (2013), s. 199-208 ISSN 1567-7249 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitocans * Anti-cancer therapeutics * Classification Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.524, year: 2013

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

    African Journals Online (AJOL)

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

  8. Identification of novel anticancer terpenoids from Prosopis juliflora ...

    African Journals Online (AJOL)

    Purpose: To identify a novel source of terpenoid anticancer compounds from P. juliflora (Sw.) DC. (Leguminosae) pods as a medicinal substitute for cancer medicines. Methods: The pods were collected, dried and pulverized. The ethanol extract was prepared by maceration. Various phyto-constituents were detected in the ...

  9. Preclinical and clinical pharmacology of oral anticancer drugs

    NARCIS (Netherlands)

    Oostendorp, R.L.

    2009-01-01

    Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for

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

    African Journals Online (AJOL)

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

  11. Pricing appraisal of anti-cancer drugs in the South East Asian, Western Pacific and East Mediterranean Region.

    Science.gov (United States)

    Salmasi, Shahrzad; Lee, Kah Seng; Ming, Long Chiau; Neoh, Chin Fen; Elrggal, Mahmoud E; Babar, Zaheer-Ud- Din; Khan, Tahir Mehmood; Hadi, Muhammad Abdul

    2017-12-28

    Globally, cancer is one of the leading causes of mortality. High treatment cost, partly owing to higher prices of anti-cancer drugs, presents a significant burden on patients and healthcare systems. The aim of the present study was to survey and compare retail prices of anti-cancer drugs between high, middle and low income countries in the South-East Asia, Western Pacific and Eastern Mediterranean regions. Cross-sectional survey design was used for the present study. Pricing data from ten counties including one from South-East Asia, two from Western Pacific and seven from Eastern Mediterranean regions were used in this study. Purchasing power parity (PPP)-adjusted mean unit prices for 26 anti-cancer drug presentations (similar pharmaceutical form, strength, and pack size) were used to compare prices of anti-cancer drugs across three regions. A structured form was used to extract relevant data. Data were entered and analysed using Microsoft Excel®. Overall, Taiwan had the lowest mean unit prices while Oman had the highest prices. Six (23.1%) and nine (34.6%) drug presentations had a mean unit price below US$100 and between US$100 and US$500 respectively. Eight drug presentations (30.7%) had a mean unit price of more than US$1000 including cabazitaxel with a mean unit price of $17,304.9/vial. There was a direct relationship between income category of the countries and their mean unit price; low-income countries had lower mean unit prices. The average PPP-adjusted unit prices for countries based on their income level were as follows: low middle-income countries (LMICs): US$814.07; high middle income countries (HMICs): US$1150.63; and high income countries (HICs): US$1148.19. There is a great variation in pricing of anticancer drugs in selected countires and within their respective regions. These findings will allow policy makers to compare prices of anti-cancer agents with neighbouring countries and develop policies to ensure accessibility and affordability of

  12. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

    Science.gov (United States)

    Dai, Shao-Xing; Li, Wen-Xing; Han, Fei-Fei; Guo, Yi-Cheng; Zheng, Jun-Juan; Liu, Jia-Qian; Wang, Qian; Gao, Yue-Dong; Li, Gong-Hua; Huang, Jing-Fei

    2016-05-01

    There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

  13. Observation and Analysis of Anti-cancer Drug Use and Dose ...

    African Journals Online (AJOL)

    As all anti-cancer drugs are of narrow therapeutic window so dose individualization is required to be done. A study was conducted to check the use of anti-cancer drugs in the local anti-cancer facility of Bahawalpur i.e. Bahawalpur Institute of Nuclear Medicine and Oncology (BINO). In this study, the dose individualization ...

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

    Science.gov (United States)

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

    2014-12-30

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

  15. 19 CFR 7.2 - Insular possessions of the United States other than Puerto Rico.

    Science.gov (United States)

    2010-04-01

    ... than Puerto Rico. 7.2 Section 7.2 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF... NAVAL STATION § 7.2 Insular possessions of the United States other than Puerto Rico. (a) Insular possessions of the United States other than Puerto Rico are also American territory but, because those insular...

  16. 50 CFR 92.6 - Use and possession of migratory birds.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Use and possession of migratory birds. 92... INTERIOR (CONTINUED) MISCELLANEOUS PROVISIONS MIGRATORY BIRD SUBSISTENCE HARVEST IN ALASKA General Provisions § 92.6 Use and possession of migratory birds. You may not sell, offer for sale, purchase, or offer...

  17. 50 CFR 600.1204 - Shark finning; possession at sea and landing of shark fins.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Shark finning; possession at sea and landing of shark fins. 600.1204 Section 600.1204 Wildlife and Fisheries FISHERY CONSERVATION AND... PROVISIONS Shark Finning § 600.1204 Shark finning; possession at sea and landing of shark fins. (a)(1) No...

  18. 10 CFR 70.20a - General license to possess special nuclear material for transport.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false General license to possess special nuclear material for transport. 70.20a Section 70.20a Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF... transport. (a) A general license is issued to any person to possess formula quantities of strategic special...

  19. Stability properties of solutions to nonlinear models possessing a sign-undefined metric

    International Nuclear Information System (INIS)

    Barashenkov, I.V.

    1983-01-01

    Multicomponent field systems possessing a sign-undefined internal space metric, in particular models with a noncompact global invariance group are investigated. It is shown that the energy cannot have even a conditional relative minimum. It is demonstrated, nevertheless, that the corresponding nonlinear equations of motion are permitted to possess stable particle-like solutions

  20. Stability properties of solutions to nonlinear models possessing a sign-undefined metric

    International Nuclear Information System (INIS)

    Barashenkov, I.V.

    1983-01-01

    Multicomponent field systems possessing a sign-undefined internal space metric, in particular models with a noncompact global invariance group, are investigated. It is shown that the energy cannot have even a conditional relative minimum. It is demonstrated, nevertheless, that the corresponding nonlinear equations of motion are permitted to possess stable particle-like solutions. (Auth.)

  1. The Regulation of the Possession of Weapons at Gatherings | du Toit

    African Journals Online (AJOL)

    The Act also amends the Regulation of Gatherings Act 205 of 1993 to prohibit the possession of any dangerous weapon at a gathering or demonstration. ... (b) possession of dangerous weapons during the participation in any religious or cultural activities or lawful sport, recreation or entertainment or (c) legitimate collection, ...

  2. The expected value of possession in professional rugby league match-play.

    Science.gov (United States)

    Kempton, Thomas; Kennedy, Nicholas; Coutts, Aaron J

    2016-01-01

    This study estimated the expected point value for starting possessions in different field locations during rugby league match-play and calculated the mean expected points for each subsequent play during the possession. It also examined the origin of tries scored according to the method of gaining possession. Play-by-play data were taken from all 768 regular-season National Rugby League (NRL) matches during 2010-2013. A probabilistic model estimated the expected point outcome based on the net difference in points scored by a team in possession in a given situation. An iterative method was used to approximate the value of each situation based on actual scoring outcomes. Possessions commencing close to the opposition's goal-line had the highest expected point equity, which decreased as the location of the possession moved towards the team's own goal-line. Possessions following an opposition error, penalty or goal-line dropout had the highest likelihood of a try being scored on the set subsequent to their occurrence. In contrast, possessions that follow an opposition completed set or a restart were least likely to result in a try. The expected point values framework from our model has applications for informing playing strategy and assessing individual and team performance in professional rugby league.

  3. Are symptoms of spirit possessed patients covered by the DSM-IV or DSM-5 criteria for possession trance disorder? A mixed-method explorative study in Uganda.

    Science.gov (United States)

    van Duijl, Marjolein; Kleijn, Wim; de Jong, Joop

    2013-09-01

    As in many cultures, spirit possession is a common idiom of distress in Uganda. The DSM-IV contains experimental research criteria for dissociative and possession trance disorder (DTD and PTD), which are under review for the DSM-5. In the current proposed categories of the DSM-5, PTD is subsumed under dissociative identity disorder (DID) and DTD under dissociative disorders not elsewhere classified. Evaluation of these criteria is currently urgently required. This study explores the match between local symptoms of spirit possession in Uganda and experimental research criteria for PTD in the DSM-IV and proposed criteria for DID in the DSM-5. A mixed-method approach was used combining qualitative and quantitative research methods. Local symptoms were explored of 119 spirit possessed patients, using illness narratives and a cultural dissociative symptoms' checklist. Possible meaningful clusters of symptoms were inventoried through multiple correspondence analysis. Finally, local symptoms were compared with experimental criteria for PTD in the DSM-IV and proposed criteria for DID in the DSM-5. Illness narratives revealed different phases of spirit possession, with passive-influence experiences preceding the actual possession states. Multiple correspondence analysis of symptoms revealed two dimensions: 'passive' and 'active' symptoms. Local symptoms, such as changes in consciousness, shaking movements, and talking in a voice attributed to spirits, match with DSM-IV-PTD and DSM-5-DID criteria. Passive-influence experiences, such as feeling influenced or held by powers from outside, strange dreams, and hearing voices, deserve to be more explicitly described in the proposed criteria for DID in the DSM-5. The suggested incorporation of PTD in DID in the DSM-5 and the envisioned separation of DTD and PTD in two distinctive categories have disputable aspects.

  4. A functional perspective of nitazoxanide as a potential anticancer drug

    International Nuclear Information System (INIS)

    Di Santo, Nicola; Ehrisman, Jessie

    2014-01-01

    Highlights: • Combination anti-cancer therapies are associated with increased toxicity and cross-resistance. • Some antiparasitic compounds may have anti-cancer potential. • Nitazoxanide interferes with metabolic and pro-death signaling. • Preclinical studies are needed to confirm anticancer ability of nitazoxanide. - Abstract: Cancer is a group of diseases characterized by uncontrolled cell proliferation, evasion of cell death and the ability to invade and disrupt vital tissue function. The classic model of carcinogenesis describes successive clonal expansion driven by the accumulation of mutations that eliminate restraints on proliferation and cell survival. It has been proposed that during cancer's development, the loose-knit colonies of only partially differentiated cells display some unicellular/prokaryotic behavior reminiscent of robust ancient life forms. The seeming “regression” of cancer cells involves changes within metabolic machinery and survival strategies. This atavist change in physiology enables cancer cells to behave as selfish “neo-endo-parasites” that exploit the tumor stromal cells in order to extract nutrients from the surrounding microenvironment. In this framework, it is conceivable that anti-parasitic compounds might serve as promising anticancer drugs. Nitazoxanide (NTZ), a thiazolide compound, has shown antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. NTZ has also been successfully used to promote Hepatitis C virus (HCV) elimination by improving interferon signaling and promoting autophagy. More compelling however are the potential anti-cancer properties that have been observed. NTZ seems to be able to interfere with crucial metabolic and pro-death signaling such as drug detoxification, unfolded protein response (UPR), autophagy, anti-cytokine activities and c-Myc inhibition. In this article, we review the ability of NTZ to interfere with integrated survival mechanisms of

  5. A functional perspective of nitazoxanide as a potential anticancer drug

    Energy Technology Data Exchange (ETDEWEB)

    Di Santo, Nicola, E-mail: nico.disanto@duke.edu; Ehrisman, Jessie, E-mail: jessie.ehrisman@duke.edu

    2014-10-15

    Highlights: • Combination anti-cancer therapies are associated with increased toxicity and cross-resistance. • Some antiparasitic compounds may have anti-cancer potential. • Nitazoxanide interferes with metabolic and pro-death signaling. • Preclinical studies are needed to confirm anticancer ability of nitazoxanide. - Abstract: Cancer is a group of diseases characterized by uncontrolled cell proliferation, evasion of cell death and the ability to invade and disrupt vital tissue function. The classic model of carcinogenesis describes successive clonal expansion driven by the accumulation of mutations that eliminate restraints on proliferation and cell survival. It has been proposed that during cancer's development, the loose-knit colonies of only partially differentiated cells display some unicellular/prokaryotic behavior reminiscent of robust ancient life forms. The seeming “regression” of cancer cells involves changes within metabolic machinery and survival strategies. This atavist change in physiology enables cancer cells to behave as selfish “neo-endo-parasites” that exploit the tumor stromal cells in order to extract nutrients from the surrounding microenvironment. In this framework, it is conceivable that anti-parasitic compounds might serve as promising anticancer drugs. Nitazoxanide (NTZ), a thiazolide compound, has shown antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. NTZ has also been successfully used to promote Hepatitis C virus (HCV) elimination by improving interferon signaling and promoting autophagy. More compelling however are the potential anti-cancer properties that have been observed. NTZ seems to be able to interfere with crucial metabolic and pro-death signaling such as drug detoxification, unfolded protein response (UPR), autophagy, anti-cytokine activities and c-Myc inhibition. In this article, we review the ability of NTZ to interfere with integrated survival mechanisms of

  6. Chemical profiles and anticancer effects of saponin fractions of different polarity from the leaves of Panax notoginseng.

    Science.gov (United States)

    Qian, Mao; Yi, Li; Song-Lin, Li; Jie, Yang; Ping-Hu, Zhang; Qiang, Wang

    2014-01-01

    To evaluate the chemical profiles and cytotoxic effects among the total saponin fraction (TSF), 25% ethanol fraction (25EF), 50% ethanol fraction (50EF), and 85% ethanol fraction (85EF) prepared by macroporous resin from the leaves of Panax notoginseng. The simultaneous determination of thirteen main saponins, as well as the chemical profiles of saponin fractions of different polarity, was made by HPLC-DAD and LC-ESI-MS(n) analysis. The cytotoxic effects were determined against KP4 cells (human pancreatic cancer), NCI-H727 cells (human lung cancer), HepG2 cells (human hepatocellular cancer), and SGC-7901 cells (human gastric adenocarcinoma). Chemical analysis indicated that 85EF possessed the most abundant cytotoxic protopanaxadiol saponins, including the marker saponins F2, 20(R)-Rg3, 20(S)-Rg3, and Rh2. The MTT assay showed that 85EF also had the strongest cytotoxic effects among the four fractions. 25EF showed no anti-proliferative effects, while 50EF and TSF exhibited weak anti-proliferative activity. From the aspect of comprehensive utilization of resources, 85EF, enriched with low polarity PPD group saponins, is a new alternative source of anticancer saponins, and a promising botanical preparation for further anticancer studies. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  7. In vitro evaluation of anticancer potentials of lupeol isolated from Elephantopus scaber L. on MCF-7 cell line

    Directory of Open Access Journals (Sweden)

    Daisy Pitchai

    2014-01-01

    Full Text Available Lupeol is a triterpenoid, present in most of the medicinally effective plants and possess a wide range of biological activity against human diseases. The present study aims at evaluating the anticancer potentials of lupeol, isolated from the leaves of Elephantopus scaber L. and thereby explores its action on key cancer marker, Bcl-2. The effect of lupeol on the cell viability of MCF-7 was determined by MTT and lactate dehydrogenase assays at different concentrations. The efficacy of the compound to induce cell death was analyzed using AO/EtBr staining. Phase contrast microscopic analysis provided the changes in cell morphology of the compound treated normal breast cells (MCF-10A and MCF-7 cells. The expression of Bcl-2 and Bcl-xL proteins in the normal, cancer and lupeol treated cancer cell was analyzed by western blotting. Lupeol induced an effective change in the cell viability of MCF-7 cells with IC 50 concentration as 80 μM. Induction of cell death, change in cell morphology and population of the cancer cells was observed in the lupeol treated cells, but the normal cells were not affected. The compound effectively downregulated Bcl-2 and Bcl-xL protein expressions, which directly contribute for the induction of MCF-7 cell apoptosis. Conclusion: Thus, lupeol acts as an anticancer agent against MCF-7 cells and is a potent phytodrug to be explored further for its cytotoxic mechanism.

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  10. "Satan has afflicted me!" Jinn-possession and mental illness in the Qur'an.

    Science.gov (United States)

    Islam, F; Campbell, R A

    2014-02-01

    Mental health stigma in Muslim communities may be partly due to a commonly held belief among some Muslims about the supernatural causes of mental illness (i.e. jinn-possession brought on by one's sinful life). A thematic analysis was carried out on four English translations and the Arabic text of the Qur'an to explore whether the connection between jinn-possession and insanity exists within the Muslim holy book. No connection between spirit-possession and madness or mental illness was found. Pagans taunted and labelled people as jinn-possessed only to ostracize and scapegoat. Linking the labelling of people as jinn-possession to a pagan practice may be used to educate Muslims, so they can reassess their community's stigma towards the mentally ill.

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

    Science.gov (United States)

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

    2013-08-01

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

  12. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

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

    Science.gov (United States)

    Diab, Kawthar Ae

    2016-01-01

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

  14. The law on the streets: Evaluating the impact of Mexico's drug decriminalization reform on drug possession arrests in Tijuana, Mexico.

    Science.gov (United States)

    Arredondo, J; Gaines, T; Manian, S; Vilalta, C; Bañuelos, A; Strathdee, S A; Beletsky, L

    2018-04-01

    In 2009, Mexican Federal Government enacted "narcomenudeo" reforms decriminalizing possession of small amounts of drugs, delegating prosecution of retail drug sales to the state courts, and mandating treatment diversion for habitual drug users. There has been insufficient effort to formally assess the decriminalization policy's population-level impact, despite mounting interest in analagous reforms across the globe. Using a dataset of municipal police incident reports, we examined patterns of drug possession, and violent and non-violent crime arrests between January 2009 and December 2014. A hierarchical panel data analysis with random effects was conducted to assess the impact of narcomenudeo's drug decriminalization provision. The reforms had no significant impact on the number of drug possession or violent crime arrests, after controlling for other variables (e.g. time trends, electoral cycles, and precinct-level socioeconomic factors). Time periods directly preceding local elections were observed to be statistically associated with elevated arrest volume. Analysis of police statistics parallel prior findings that Mexico's reform decriminalizing small amounts of drugs does not appear to have significantly shifted drug law enforcement in Tijuana. More research is required to fully understand the policy transformation process for drug decriminalization and other structural interventions in Mexico and similar regional and international efforts. Observed relationship between policing and political cycles echo associations in other settings whereby law-and-order activities increase during mayoral electoral campaigns. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Lipid Accumulation in Peripheral Blood Dendritic Cells and Anticancer Immunity in Patients with Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ryo Arai

    2018-01-01

    Full Text Available We studied the subsets of peripheral blood dendritic cells (DCs and lipid accumulation in DCs to investigate the involvement of DCs in the decreased anticancer immunity of advanced lung cancer patients. We analyzed the population of DC subsets in peripheral blood using flow cytometry. We then determined lipid accumulation in the DCs using BODIPY 650/665, a fluorophore with an affinity for lipids. Compared with healthy controls, the number of DCs in the peripheral blood of treatment-naive cancer patients was significantly reduced. In patients with stage III + IV disease, the numbers of myeloid DCs (mDCs and plasmacytoid DCs were also significantly reduced. Lipid accumulation in DCs evaluated based on the fluorescence intensity of BODIPY 650/665 was significantly higher in stage III + IV lung cancer patients than in the controls. In the subset analysis, the fluorescence was highest for mDCs. The intracellularly accumulated lipids were identified as triglycerides. A decreased mixed leukocyte reaction was observed in the mDCs from lung cancer patients compared with those from controls. Taken together, the results show that lung cancer patients have a notably decreased number of peripheral blood DCs and their function as antigen-presenting cells is decreased due to their high intracellular lipid accumulation. Thereby, anticancer immunity is suppressed.

  16. Eco-friendly biosynthesis, anticancer drug loading and cytotoxic effect of capped Ag-nanoparticles against breast cancer

    Science.gov (United States)

    Naz, M.; Nasiri, N.; Ikram, M.; Nafees, M.; Qureshi, M. Z.; Ali, S.; Tricoli, A.

    2017-11-01

    The work aimed to prepare silver nanoparticles (Ag-NPs) from silver nitrate and various concentrations of the seed extract ( Setaria verticillata) by a green synthetic route. The chemical and physical properties of the resulting Ag-NPs were investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectrometry and ultraviolet-visible (UV-Vis) spectrophotometry. Anticancer activity of Ag-NPs (5-20 nm) had dose-dependent cytotoxic effect against breast cancer (MCF7-FLV) cells. The in vitro toxicity was studied on adult earthworms (Lumbricina) resulting in statistically significant ( P < 0.05) inhibition. The prepared NPs were loaded with hydrophilic anticancer drugs (ACD), doxorubicin (DOX) and daunorubicin (DNR), for developing a novel drug delivery carrier having significant adsorption capacity and efficiency to remove the side effects of the medicines effective for leukemia chemotherapy.

  17. Delivery Systems for Birch-Bark Triterpenoids and Their Derivatives in Anticancer Research.

    Science.gov (United States)

    Mierina, Inese; Vilskersts, Reinis; Turks, Maris

    2018-05-29

    Birch-bark triterpenoids and their semi-synthetic derivatives possess a wide range of biological activities including cytotoxic effects on various tumour cell lines. However, due to the low solubility and bioavailability, their medicinal applications are rather limited. The use of various nanotechnology-based drug delivery systems is rapidly developing approach to the solubilisation of insufficiently bioavailable pharmaceuticals. Herein, the drug delivery systems deemed to be applicable for birch-bark triterpenoid structures are reviewed. The aforementioned disadvantages of birch-bark triterpenoids and their semi-synthetic derivatives can be overcome through their incorporation into organic nanoparticles, which include various dendrimeric systems, as well as embedding the active compounds into polymer matrices or complexation with carbohydrate nanoparticles without covalent bonding. Some of the known triterpenoid delivery systems consist of nanoparticles featuring inorganic cores covered with carbohydrates or other polymers. Methods for delivering the title compounds through encapsulation and emulsification into lipophilic media are also suitable. Besides, the birch-bark triterpenoids can form self-assembling systems with increased bio-availability. Even more, the self-assembling systems are used as carriers for delivering other chemotherapeutic agents. Another advantage besides increased bioavailability and anticancer activity is the reduced overall systemic toxicity in most of the cases, when triterpenoids are delivered with any of the carriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Directory of Open Access Journals (Sweden)

    R Kowsalya

    2015-01-01

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

  19. Anticancer Potential of Nutraceutical Formulations in MNU-induced Mammary Cancer in Sprague Dawley Rats.

    Science.gov (United States)

    Pitchaiah, Gummalla; Akula, Annapurna; Chandi, Vishala

    2017-01-01

    Nutraceuticals help in combating some of the major health problems of the century including cancer, and 'nutraceutical formulations' have led to the new era of medicine and health. To develop different nutraceutical formulations and to assess the anticancer potential of nutraceutical formulations in N-methyl-N-nitrosourea (MNU)-induced mammary cancer in Sprague Dawley rats. Different nutraceutical formulations were prepared using fine powders of amla, apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Improvement in total phenolic content was significant ( P safe to use in animals. Microbial load was within the limits. Significant longer tumor-free days ( P apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Improvement in total phenolic content was observed after self-fortification process. Toxicity studies showed that the nutraceutical formulations were safe to use in animals. Microbial load was within the limits. Longer tumor-free days, lower tumor incidence, lower tumor multiplicity and tumor burden were observed for nutraceutical formulation-treated groups. This suggests that combination of whole food-based nutraceuticals acted synergistically in the prevention of mammary cancer. Further, the process of fortification enhanced the anticancer potential of nutraceutical formulations. Abbreviations used: HMNU: N-methyl-N-nitrosourea, CAM: Complementary and Alternative Medicine, NF: Nutraceutical

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

    Science.gov (United States)

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

    2018-06-01

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

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

    OpenAIRE

    Md. Azizur Rahman; Arshad Hussain

    2015-01-01

    MTT assay and DAPI staining test were performed to evaluate anticancer potential and to assess apoptosis inducing effect of methanolic extract of Cordia dichotoma leaves (MECD) against human cervical cancer cell line (HeLa). Changes in MMP and intracellular ROS level were also assessed by JC-1 and DCFH-DA staining. Total phenolic contents were determined by colorimetric principle. Levels of statistical significance were determined by one-way analysis of variance followed by Dunnett’s posttest...

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2012-12-05

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

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

    Science.gov (United States)

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

    2013-06-01

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

  5. Cdt1 is differentially targeted for degradation by anticancer chemotherapeutic drugs.

    Directory of Open Access Journals (Sweden)

    Athanasia Stathopoulou

    Full Text Available BACKGROUND: Maintenance of genome integrity is crucial for the propagation of the genetic information. Cdt1 is a major component of the pre-replicative complex, which controls once per cell cycle DNA replication. Upon DNA damage, Cdt1 is rapidly targeted for degradation. This targeting has been suggested to safeguard genomic integrity and prevent re-replication while DNA repair is in progress. Cdt1 is deregulated in tumor specimens, while its aberrant expression is linked with aneuploidy and promotes tumorigenesis in animal models. The induction of lesions in DNA is a common mechanism by which many cytotoxic anticancer agents operate, leading to cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDING: In the present study we examine the ability of several anticancer drugs to target Cdt1 for degradation. We show that treatment of HeLa and HepG2 cells with MMS, Cisplatin and Doxorubicin lead to rapid proteolysis of Cdt1, whereas treatment with 5-Fluorouracil and Tamoxifen leave Cdt1 expression unaffected. Etoposide affects Cdt1 stability in HepG2 cells and not in HeLa cells. RNAi experiments suggest that Cdt1 proteolysis in response to MMS depends on the presence of the sliding clamp PCNA. CONCLUSION/SIGNIFICANCE: Our data suggest that treatment of tumor cells with commonly used chemotherapeutic agents induces differential responses with respect to Cdt1 proteolysis. Information on specific cellular targets in response to distinct anticancer chemotherapeutic drugs in different cancer cell types may contribute to the optimization of the efficacy of chemotherapy.

  6. Physicochemical investigations of biogenic chitosan-silver nanocomposite as antimicrobial and anticancer agent.

    Science.gov (United States)

    Arjunan, Nithya; Kumari, Henry Linda Jeeva; Singaravelu, Chandra Mohan; Kandasamy, Ruckmani; Kandasamy, Jothivenkatachalam

    2016-11-01

    Chitosan (CS), a seaweed polysaccharide is a natural macromolecule which is widely being used in medical applications because of its distinctive antimicrobial and anticancer properties. Silver, a noble metal, is also receiving wide attention for its potential usage in antimicrobial and anticancer therapeutics. In this study, an effective way of reduction of silver using chitosan at varying reaction temperatures and an optimised concentration of silver were performed. The optical, structural, spectral, morphological and elemental studies of the biosynthesized chitosan-silver (CS-Ag) nanocomposites were characterized by several techniques. The synthesized CS-Ag nanocomposites exhibit particle size around 20nm and were further exploited for potent biological applications in nanomedicine due to their nanometric sizes and biocompatibility of chitosan. The antimicrobial activity of the biosynthesized CS-Ag nanocomposites exhibits zone of inhibition ranged between 09.666±0.577 and 19.000±1.000 (mm). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were from 8 to 128μgmL -1 and 16 to 256μgmL -1 respectively, with the highest antimicrobial activity shown against Gram-negative Salmonella sp. The synergistic effect of chitosan and silver as a composite in nanometric size revealed significant IC 50 value of 29.35μgmL -1 and a maximum of 95.56% inhibition at 100μgmL -1 against A549 lung cancer cell line, resulting in potent anticancer effect. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Qin

    2015-11-01

    Full Text Available Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1, phloretin (A2, 3-hydroxyphloretin (A3, phloretin rutinoside (A4, phlorizin (A5, 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6, and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7, all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity.

  8. Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

    Science.gov (United States)

    Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

    2013-07-01

    Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

  9. Molecular Biological Study of Anti-cancer Effects of Bee Venom Aqua-acupuncture

    Directory of Open Access Journals (Sweden)

    Park Chan-Yol

    2000-07-01

    Full Text Available To study anti-cancer effect and molecular biological mechanism of bee venom for aqua-acupuncture, the effects of bee venom on cell viability and apoptosis were analyzed using MTT assay, tryphan blue assay, [3H]thymidine release assay, flow cytometric analysis, and activity of caspase-3 protease activity assay. To explore whether anti-cancer effects of bee venom are associated with the transcriptional control of gene expression, quantitative RT-PCR analysis of apoptosis-related genes was performed. The obtained results are summarized as follows: 1. The MTT assay demonstrated that cell viability was decreased by bee venom in a dose-dependant manner. 2. Significant induction of apoptosis was identified using tryphan blue assay, [3H]thymidine release assay, and flow cytometric analysis of sub G1 fraction. 3. In analysis of caspase-3 protease activity, the activity had increased significantly, in a dose-dependant manner. 4. Quantitative RT-PCR analysis of the apoptosis-related genes showed that Bcl-2 and Bcl-XL were down-regulated whereas Bax was up-regulated by bee venom treatment.

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

    Directory of Open Access Journals (Sweden)

    Antonella Rosa

    2015-01-01

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

  11. HLBT-100: a highly potent anti-cancer flavanone from Tillandsia recurvata (L.) L.

    Science.gov (United States)

    Lowe, Henry I C; Toyang, Ngeh J; Watson, Charah T; Ayeah, Kenneth N; Bryant, Joseph

    2017-01-01

    The incidence and mortalities from cancers remain on the rise worldwide. Despite significant efforts to discover and develop novel anticancer agents, many cancers remain in the unmet need category. As such, efforts to discover and develop new and more effective and less toxic agents against cancer remain a top global priority. Our drug discovery approach is natural products based with a focus on plants. Tillandsia recurvata (L.) L. is one of the plants selected by our research team for further studies based on previous bioactivity findings on the anticancer activity of this plant. The plant biomass was extracted using supercritical fluid extraction technology with CO 2 as the mobile phase. Bioactivity guided isolation was achieved by use of chromatographic technics combined with anti-proliferative assays to determine the active fraction and subsequently the pure compound. Following in house screening, the identified molecule was submitted to the US National Cancer Institute for screening on the NCI60 cell line panel using standard protocols. Effect of HLBT-100 on apoptosis, caspase 3/7, cell cycle and DNA fragmentation were assessed using standard protocols. Antiangiogenic activity was carried out using the ex vivo rat aortic ring assay. A flavonoid of the flavanone class was isolated from T. recurvata (L.) L. with potent anticancer activity. The molecule was code named as HLBT-100 (also referred to as HLBT-001). The compound inhibited brain cancer (U87 MG), breast cancer (MDA-MB231), leukemia (MV4-11), melanoma (A375), and neuroblastoma (IMR-32) with IC 50 concentrations of 0.054, 0.030, 0.024, 0.003 and 0.05 µM, respectively. The molecule also exhibited broad anticancer activity in the NCI60 panel inhibiting especially hematological, colon, CNS, melanoma, ovarian, breast and prostate cancers. Twenty-three of the NCI60 cell lines were inhibited with GI 50 values <0.100 µM. In terms of potential mechanisms of action, the molecule demonstrated effect on the

  12. Unraveling the Anticancer Effect of Curcumin and Resveratrol

    Science.gov (United States)

    Pavan, Aline Renata; da Silva, Gabriel Dalio Bernardes; Jornada, Daniela Hartmann; Chiba, Diego Eidy; Fernandes, Guilherme Felipe dos Santos; Man Chin, Chung; dos Santos, Jean Leandro

    2016-01-01

    Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unravel the molecular mechanism of action of both compounds. Molecular targets and cellular pathways will be described. Furthermore, we also discussed the ability of these natural products act as chemopreventive and its use in association with other anticancer drugs. PMID:27834913

  13. Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications.

    Science.gov (United States)

    Camorani, Simona; Crescenzi, Elvira; Fedele, Monica; Cerchia, Laura

    2018-04-01

    Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell proliferation, survival, migration and differentiation. Area of intense research is searching for effective anticancer therapies targeting these receptors and, to date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors have entered the clinic. However, some of these drugs show limited efficacy and give rise to acquired resistance. Emerging highly selective compounds for anticancer therapy are oligonucleotide aptamers that interact with their targets by recognizing a specific three-dimensional structure. Because of their nucleic acid nature, the rational design of advanced strategies to manipulate aptamers for both diagnostic and therapeutic applications is greatly simplified over antibodies. In this manuscript, we will provide a comprehensive overview of oligonucleotide aptamers as next generation strategies to efficiently target RTKs in human cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Botanical, Phytochemical, and Anticancer Properties of the Eucalyptus Species.

    Science.gov (United States)

    Vuong, Quan V; Chalmers, Anita C; Jyoti Bhuyan, Deep; Bowyer, Michael C; Scarlett, Christopher J

    2015-06-01

    The genus Eucalyptus (Myrtaceae) is mainly native to Australia; however, some species are now distributed globally. Eucalyptus has been used in indigenous Australian medicines for the treatment of a range of aliments including colds, flu, fever, muscular aches, sores, internal pains, and inflammation. Eucalyptus oils containing volatile compounds have been widely used in the pharmaceutical and cosmetics industries for a multitude of purposes. In addition, Eucalyptus extracts containing nonvolatile compounds are also an important source of key bioactive compounds, and several studies have linked Eucalyptus extracts with anticancer properties. With the increasing research interest in Eucalyptus and its health properties, this review briefly outlines the botanical features of Eucalyptus, discusses its traditional use as medicine, and comprehensively reviews its phytochemical and anticancer properties and, finally, proposes trends for future studies. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

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

    KAUST Repository

    Sagar, Sunil

    2010-09-01

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

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

    KAUST Repository

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

    2010-01-01

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

  17. Trial watch: Naked and vectored DNA-based anticancer vaccines.

    Science.gov (United States)

    Bloy, Norma; Buqué, Aitziber; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-05-01

    One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm.

  18. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy.

    Science.gov (United States)

    Pol, Jonathan; Vacchelli, Erika; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-04-01

    The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wen-Xi Cai

    2016-01-01

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

  1. Monitoring of anti-cancer therapies and chemoresistance

    Czech Academy of Sciences Publication Activity Database

    Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Džubák, P.; Hajdúch, M.; Gadher, S. J.; Kovářová, Hana

    2009-01-01

    Roč. 6, č. 1 (2009), s. 63-63 ISSN 1109-6535. [International Conference of the Hellenic Proteomic Society /3./. 30.03.2009-01.04.2009, Nafplio] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : anti-cancer therapies Subject RIV: CE - Biochemistry

  2. Microtubule destabilising agents: far more than just antimitotic anticancer drugs

    OpenAIRE

    Bates, Darcy; Eastman, Alan

    2016-01-01

    Vinca alkaloids have been approved as anticancer drugs for more than 50 years. They have been classified as cytotoxic chemotherapy drugs that act during cellular mitosis, enabling them to target fast growing cancer cells. With the evolution of cancer drug development there has been a shift towards new “targeted” therapies to avoid the side effects and general toxicities of “cytotoxic chemotherapies” such as the vinca alkaloids. Due to their original classification, many have overlooked the fa...

  3. 48 CFR 52.236-11 - Use and Possession Prior to Completion.

    Science.gov (United States)

    2010-10-01

    ... possession or use shall not be deemed an acceptance of any work under the contract. (b) While the Government... adjustment shall be made in the contract price or the time of completion, and the contract shall be modified...

  4. Schizophrenia-The spirit possessed 23 year old male from rural ...

    African Journals Online (AJOL)

    A case of a twenty-three year old rural Ghanaian male suffering from schizophrenia and presenting as “possessed by spirits” is reported. Treatment, and outcome by physical means with chlorpromazine; and implications for further research are discussed.

  5. 32 CFR 552.122 - Personnel not authorized to possess or retain personal weapons.

    Science.gov (United States)

    2010-07-01

    ... THE ARMY MILITARY RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS... person who has been convicted in any court of the possession, use, or sale of marijuana, dangerous or...

  6. Anticancer potential of Thevetia peruviana fruit methanolic extract.

    Science.gov (United States)

    Ramos-Silva, Alberto; Tavares-Carreón, Faviola; Figueroa, Mario; De la Torre-Zavala, Susana; Gastelum-Arellanez, Argel; Rodríguez-García, Aída; Galán-Wong, Luis J; Avilés-Arnaut, Hamlet

    2017-05-02

    Thevetia peruviana (Pers.) K. Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines. The cytotoxic activity of T. peruviana methanolic extract was carried out on human breast, colorectal, prostate and lung cancer cell lines and non-tumorigenic control cells (fibroblast and Vero), using the MTT assay. For proliferation and motility, clonogenic and wound-healing assays were performed. Morphological alterations were monitored by trypan blue exclusion, as well as DNA fragmentation and AO/EB double staining was performed to evaluate apoptosis. The extract was separated using flash chromatography, and the resulting fractions were evaluated on colorectal cancer cells for their cytotoxic activity. The active fractions were further analyzed through mass spectrometry. The T. peruviana methanolic extract exhibited cytotoxic activity on four human cancer cell lines: prostate, breast, colorectal and lung, with values of IC 50 1.91 ± 0.76, 5.78 ± 2.12, 6.30 ± 4.45 and 12.04 ± 3.43 μg/mL, respectively. The extract caused a significant reduction of cell motility and colony formation on all evaluated cancer cell lines. In addition, morphological examination displayed cell size reduction, membrane blebbing and detachment of cells, compared to non-treated cancer cell lines. The T. peruviana extract induced apoptotic cell death, which was confirmed by DNA fragmentation and AO/EB double staining. Fractions 4 and 5 showed the most effective cytotoxic activity and their MS analysis revealed the presence of the secondary metabolites: thevetiaflavone and cardiac glycosides. T. peruviana extract has

  7. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

    Science.gov (United States)

    Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

    2017-08-01

    Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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

    Science.gov (United States)

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

    2018-01-01

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

  9. Peptide-based proteasome inhibitors in anticancer drug design.

    Science.gov (United States)

    Micale, Nicola; Scarbaci, Kety; Troiano, Valeria; Ettari, Roberta; Grasso, Silvana; Zappalà, Maria

    2014-09-01

    The identification of the key role of the eukaryotic 26S proteasome in regulated intracellular proteolysis and its importance as a target in many pathological conditions wherein the proteasomal activity is defective (e.g., malignancies, autoimmune diseases, neurodegenerative diseases, etc.) prompted several research groups to the development of specific inhibitors of this multicatalytic complex with the aim of obtaining valid drug candidates. In regard to the anticancer therapy, the peptide boronate bortezomib (Velcade®) represents the first molecule approved by FDA for the treatment of multiple myeloma in 2003 and mantle cell lymphoma in 2006. Since then, a plethora of molecules targeting the proteasome have been identified as potential anticancer agents and a few of them reached clinical trials or are already in the market (i.e., carfilzomib; Kyprolis®). In most cases, the design of new proteasome inhibitors (PIs) takes into account a proven peptide or pseudopeptide motif as a base structure and places other chemical entities throughout the peptide skeleton in such a way to create an efficacious network of interactions within the catalytic sites. The purpose of this review is to provide an in-depth look at the current state of the research in the field of peptide-based PIs, specifically those ones that might find an application as anticancer agents. © 2014 Wiley Periodicals, Inc.

  10. Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Neng [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Yin, Huabing, E-mail: huabing.yin@glasgow.ac.uk [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Ji, Bozhi; Klauke, Norbert; Glidle, Andrew [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Zhang, Yongkui; Song, Hang [Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Cai, Lulu; Ma, Liang; Wang, Guangcheng [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Chen, Lijuan, E-mail: lijuan17@hotmail.com [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Wang, Wenwen [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China)

    2012-12-01

    Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: Black-Right-Pointing-Pointer BSA-doped calcium carbonate microspheres with porous structure were prepared. Black-Right-Pointing-Pointer Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. Black-Right-Pointing-Pointer The release of encapsulated camptothecin is pH dependent Black-Right-Pointing-Pointer In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

  11. Feature interpretability and the positions of 2nd person possessives in Brazilian Portuguese

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    Bruna Karla Pereira

    2016-12-01

    Full Text Available Interpretability and valuation of φ-features (Chomsky, 2001; Pesetsky and Torrego, 2007 have played a central role in the investigation of language universals. With regard to that, in standard Brazilian Portuguese (BP, as well as in other Romance languages, possessives have uninterpretable number features, which are valued via nominal agreement. However, dialects of BP, especially the one spoken in Minas Gerais, have shown that 2nd person possessives, in postnominal position, do not have number agreement with the noun. In order to account for these facts, I will argue that, in this grammar, number features on 2nd person possessives are reanalyzed as being: (i associated with the person (rather than the noun and (ii interpretable. From the first postulation, ‘seu’ is expected to be the possessive for 2nd person singular, and ‘seus’ for 2nd person plural. From the second postulation, no number concord is expected to be triggered on the possessive. In addition, based on Danon (2011 and Norris (2014, I will argue that cardinals divide BP DPs into two domains in that phrases located above NumP are marked with the plural morpheme, while phrases below it are unmarked. In this sense, because prenominal possessives precede cardinals (NumP, they must be marked with the plural morpheme for nominal agreement; whereas postnominal possessives, which follow NumP, must be unmarked. Free from the plural marking associated with nominal agreement, postnominal 2nd person possessives favor the reanalysis of the morpheme ‘-s’ as indicating the number associated with person features.

  12. Silver Nanoparticles Complexed with Bovine Submaxillary Mucin Possess Strong Antibacterial Activity and Protect against Seedling Infection.

    Science.gov (United States)

    Makarovsky, Daria; Fadeev, Ludmila; Salam, Bolaji Babajide; Zelinger, Einat; Matan, Ofra; Inbar, Jacob; Jurkevitch, Edouard; Gozin, Michael; Burdman, Saul

    2018-02-15

    A simple method for the synthesis of nanoparticles (NPs) of silver (Ag) in a matrix of bovine submaxillary mucin (BSM) was reported previously by some of the authors of this study. Based on mucin characteristics such as long-lasting stability, water solubility, and surfactant and adhesive characteristics, we hypothesized that these compounds, named BSM-Ag NPs, may possess favorable properties as potent antimicrobial agents. The goal of this study was to assess whether BSM-Ag NPs possess antibacterial activity, focusing on important plant-pathogenic bacterial strains representing both Gram-negative ( Acidovorax and Xanthomonas ) and Gram-positive ( Clavibacter ) genera. Growth inhibition and bactericidal assays, as well as electron microscopic observations, demonstrate that BSM-Ag NPs, at relatively low concentrations of silver, exert strong antimicrobial effects. Moreover, we show that treatment of melon seeds with BSM-Ag NPs effectively prevents seed-to-seedling transmission of Acidovorax citrulli , one of the most threatening pathogens of cucurbit production worldwide. Overall, our findings demonstrate strong antimicrobial activity of BSM-Ag NPs and their potential application for reducing the spread and establishment of devastating bacterial plant diseases in agriculture. IMPORTANCE Bacterial plant diseases challenge agricultural production, and the means available to manage them are limited. Importantly, many plant-pathogenic bacteria have the ability to colonize seeds, and seed-to-seedling transmission is a critical route by which bacterial plant diseases spread to new regions and countries. The significance of our study resides in the following aspects: (i) the simplicity of the method of BSM-Ag NP synthesis, (ii) the advantageous chemical properties of BSM-Ag NPs, (iii) the strong antibacterial activity of BSM-Ag NPs at relatively low concentrations of silver, and (iv) the fact that, in contrast to most studies on the effects of metal NPs on plant pathogens

  13. Does the copolymer poly(vinylidene cyanide-tricyanoethylene) possess piezoelectricity?

    Science.gov (United States)

    Wang, Zhi-Yin; Su, Ke-He; Xu, Qiong

    2012-10-01

    The geometry, energy, internal rotation barrier, dipole moment, and molecular polarizability of the α- and β-chain models of poly(vinylidene cyanide-tricyanoethylene) [P(VDCN-TrCN)] were studied with density functional theory at the B3PW91/6-31G(d) level. The effects of the chain length and the TrCN content on the copolymer chain stability, the chain conformation, and the electrical properties of P(VDCN-TrCN) were examined and compared with those of poly(vinylidene fluoride-trifluoroethylene) and PVDCN to gauge whether P(VDCN-TrCN) would be expected to possess substantial piezoelectricity. The results of this study showed that the stability of the β conformation increases and the energy difference per monomer unit between the β- and α-chains decreases with increasing TrCN. However, introducing TrCN into VDCN will not significantly enhance the radius of curvature of the P(VDCN-TrCN) chains. The average dipole moment per monomer unit in the β-chain is affected by the chain curvature and the TrCN content. The amount of piezoelectricity present in P(VDCN-TrCN) is slightly smaller than that in PVDCN, and is less than that in poly(vinylidene fluoride-trifluoroethylene).

  14. Steady nanofluid flow with variable fluid possessions over a linearly extending surface: A Lie group exploration

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    Kalidas Das

    2018-03-01

    Full Text Available The temperament of stream characteristic, heat and mass transfer of MHD forced convective flow over a linearly expanding porous medium has been scrutinized in the progress exploration. The germane possessions of the liquid like viscosity along with thermal conductivity are believed to be variable in nature, directly influenced by the temperature of flow. As soon as gaining the system of leading equations of the stream, Lie symmetric group transformations have been employed to come across the fitting parallel conversions to alter the central PDEs into a suit of ODEs. The renovated system of ODE with appropriate boundary conditions is numerically solved with the assistance of illustrative software MAPLE 17. The consequences of the relevant factors of the system have been exemplified through charts and graphs. An analogous qualified survey has been prepared among present inquiry and subsisting reads and achieved an admirable accord between them. The variable viscosity parameter has more significant effect on nanofluid velocity than regular fluid and temporal profile as well as nanoparticle concentration is also influenced with variable viscosity. Keywords: Nanofluid, Stretching sheet, Variable viscosity, Variable thermal conductivity, Lie symmetry group

  15. A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

    Science.gov (United States)

    Shak, S; Perez, H D; Goldstein, I M

    1983-12-25

    We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

  16. A comparative study on the changes of serum fibrosis indicators after TACE with use of low-dose versus conventional-dose of anticancer drugs in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Lu Wei; Li Yanhao; He Xiaofeng; Chen Yong

    2004-01-01

    Objective: To study the changes of serum fibrosis indicators after transcatheter arterial chemo-embolization (TACE) with the use of low-dose vs conventional-dose of anticancer drugs in hepatocellular carcinoma (HCC). Methods: Forty patients with HCC were divided into two groups to receive superselective TACE. Patients in group A(n=20) received low-dose anticancer drug(s): 2-4 mg mitomycin C (MMC) with the tumor mass less than 5 cm in size; while MMC 4-6 mg and epirubicin (EPI) 10 mg were given with tumor size of 5-8 cm in diameter, and MMC 6-8 mg, EPI 10 mg, CBP 100 mg with tumors larger than 8 cm. Patients in group B (n=20) were given conventional-dose of anticancer drugs (MMC 10 mg, EPI 40 mg and CBP 300 mg). Lipiodol-anticancer drugs emulsion was injected into the feeding arteries of tumors and followed by gelatin sponge or PVA particles embolization participation. Four serum fibrosis indicators, including hyaluronate acid (HA), human procollagen type-III (hPC-III), laminin (LN), collagen type-IV (IV-C) were assessed before and 7 days after TACE. Results: There was no significant difference between the two groups concerning the four indicators before TACE, but the concentrations of the four serum indicators were increased significantly in group B (P 0.05). Conclusions: The formation of liver fibrosis after TACE in HCC is related to the dosage of anticancer drugs employed for chemoembolization. Therefore, low-dose anticancer drugs should be advocated. (authors)

  17. Cytotoxic protein from the mushroom Coprinus comatus possesses a unique mode for glycan binding and specificity

    Science.gov (United States)

    Zhang, Peilan; Yang, Guang; Xia, Changqing; Polston, Jane E.; Li, Gengnan; Li, Shiwu; Lin, Zhao; Yang, Li-jun; Bruner, Steven D.

    2017-01-01

    Glycans possess significant chemical diversity; glycan binding proteins (GBPs) recognize specific glycans to translate their structures to functions in various physiological and pathological processes. Therefore, the discovery and characterization of novel GBPs and characterization of glycan–GBP interactions are significant to provide potential targets for therapeutic intervention of many diseases. Here, we report the biochemical, functional, and structural characterization of a 130-amino-acid protein, Y3, from the mushroom Coprinus comatus. Biochemical studies of recombinant Y3 from a yeast expression system demonstrated the protein is a unique GBP. Additionally, we show that Y3 exhibits selective and potent cytotoxicity toward human T-cell leukemia Jurkat cells compared with a panel of cancer cell lines via inducing caspase-dependent apoptosis. Screening of a glycan array demonstrated GalNAcβ1–4(Fucα1–3)GlcNAc (LDNF) as a specific Y3-binding ligand. To provide a structural basis for function, the crystal structure was solved to a resolution of 1.2 Å, revealing a single-domain αβα-sandwich motif. Two monomers were dimerized to form a large 10-stranded, antiparallel β-sheet flanked by α-helices on each side, representing a unique oligomerization mode among GBPs. A large glycan binding pocket extends into the dimeric interface, and docking of LDNF identified key residues for glycan interactions. Disruption of residues predicted to be involved in LDNF/Y3 interactions resulted in the significant loss of binding to Jurkat T-cells and severely impaired their cytotoxicity. Collectively, these results demonstrate Y3 to be a GBP with selective cytotoxicity toward human T-cell leukemia cells and indicate its potential use in cancer diagnosis and treatment. PMID:28784797

  18. Cytotoxic protein from the mushroom Coprinus comatus possesses a unique mode for glycan binding and specificity.

    Science.gov (United States)

    Zhang, Peilan; Li, Kunhua; Yang, Guang; Xia, Changqing; Polston, Jane E; Li, Gengnan; Li, Shiwu; Lin, Zhao; Yang, Li-Jun; Bruner, Steven D; Ding, Yousong

    2017-08-22

    Glycans possess significant chemical diversity; glycan binding proteins (GBPs) recognize specific glycans to translate their structures to functions in various physiological and pathological processes. Therefore, the discovery and characterization of novel GBPs and characterization of glycan-GBP interactions are significant to provide potential targets for therapeutic intervention of many diseases. Here, we report the biochemical, functional, and structural characterization of a 130-amino-acid protein, Y3, from the mushroom Coprinus comatus Biochemical studies of recombinant Y3 from a yeast expression system demonstrated the protein is a unique GBP. Additionally, we show that Y3 exhibits selective and potent cytotoxicity toward human T-cell leukemia Jurkat cells compared with a panel of cancer cell lines via inducing caspase-dependent apoptosis. Screening of a glycan array demonstrated GalNAcβ1-4(Fucα1-3)GlcNAc (LDNF) as a specific Y3-binding ligand. To provide a structural basis for function, the crystal structure was solved to a resolution of 1.2 Å, revealing a single-domain αβα-sandwich motif. Two monomers were dimerized to form a large 10-stranded, antiparallel β-sheet flanked by α-helices on each side, representing a unique oligomerization mode among GBPs. A large glycan binding pocket extends into the dimeric interface, and docking of LDNF identified key residues for glycan interactions. Disruption of residues predicted to be involved in LDNF/Y3 interactions resulted in the significant loss of binding to Jurkat T-cells and severely impaired their cytotoxicity. Collectively, these results demonstrate Y3 to be a GBP with selective cytotoxicity toward human T-cell leukemia cells and indicate its potential use in cancer diagnosis and treatment.

  19. In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS) from Sea Cucumber Cucumaria frondosa.

    Science.gov (United States)

    Liu, Xiaoxiao; Liu, Yong; Hao, Jiejie; Zhao, Xiaoliang; Lang, Yinzhi; Fan, Fei; Cai, Chao; Li, Guoyun; Zhang, Lijuan; Yu, Guangli

    2016-05-12

    The low-molecular-weight fucosylated chondroitin sulfate (LFCS) was prepared from native fucosylated chondroitin sulfate (FCS), which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC) was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF), increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and downregulated the matrix metalloproteinases (MMPs) level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-κB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study.

  20. In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS from Sea Cucumber Cucumaria frondosa

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Liu

    2016-05-01

    Full Text Available The low-molecular-weight fucosylated chondroitin sulfate (LFCS was prepared from native fucosylated chondroitin sulfate (FCS, which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF, increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1 and downregulated the matrix metalloproteinases (MMPs level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-κB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study.

  1. Au/TiO2 nanobelt heterostructures for the detection of cancer cells and anticancer drug activity by potential sensing

    International Nuclear Information System (INIS)

    Cui, Jingjie; Xu, Ping; Li, Hong; Chen, Jing; Chen, Shaowei; Gao, Li

    2016-01-01

    Cancer is a cell dysfunction disease. The detection of cancer cells is extremely important for early diagnosis and clinical treatments. At present, the pretreatment for the detection of cancer cells is costly, complicated and time-consuming. As different species of the analytes may give rise to specific voltammetric signals at distinctly different potentials, simple potential sensing has the specificity to detect different cellular species. By taking advantage of the different electrochemical characteristics of normal cells, cancer cells and biointeractions between anticancer drugs and cancer cells, we develop a specific, sensitive, direct, cost-effective and rapid method for the detection of cancer cells by electrochemical potential sensing based on Au/TiO 2 nanobelt heterostructure electrodes that will be of significance in early cancer diagnosis, in vitro screening of anticancer drugs  and molecular biology research. (paper)

  2. O olhar dos psiquiatras brasileiros sobre os fenômenos de transe e possessão Brazilian psychiatrists’ approaches on trance and possession phenomena

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    Angélica A. Silva de Almeida

    2007-01-01

    Full Text Available CONTEXTO: Os fenômenos de transe e possessão despertaram o interesse da comunidade psiquiátrica brasileira, gerando posturas diversificadas. OBJETIVOS: Descrever e analisar como os fenômenos de transe e possessão foram tratados pelos psiquiatras brasileiros: seu impacto na teoria, na pesquisa e na prática clínica entre 1900 e 1950. MÉTODO: Análise de artigos científicos e leigos, teses e livros sobre transes e possessões produzidos pelos psiquiatras brasileiros entre 1900 e 1950. RESULTADOS: Identificam-se duas correntes de pensamento entre os psiquiatras. A primeira, vinculada às Faculdades de Medicina do Rio de Janeiro e São Paulo, sob forte influência de autores franceses, deteve-se mais na periculosidade do espiritismo para a saúde mental. Defendia a adoção de medidas repressivas com o poder público. O segundo grupo de psiquiatras, ligado às Faculdades de Medicina da Bahia e Pernambuco, embora não desconsiderasse o caráter patológico ou "primitivo" dos fenômenos de transe e possessão, apresentou uma visão mais antropológica e culturalista. Considerando tais fenômenos como manifestações étnicas ou culturais, alguns defenderam o controle médico e a educação do povo para o abandono dessas práticas "primitivas". Outros não consideravam os fenômenos mediúnicos como desencadeadores da loucura, mas manifestações não-patológicas de um universo cultural, além de não vinculá-los ao atraso cultural da população. CONCLUSÕES: As religiões mediúnicas foram objeto de estudo por longo período, resultando hipóteses e práticas diferenciadas por parte da comunidade psiquiátrica brasileira, constituindo-se oportunidade privilegiada para o estudo do impacto dos fatores socioculturais na atividade psiquiátrica.BACKGROUND: Trance and possession experiences have raised interest among Brazilian psychiatrists resulting in a variety of approaches. OBJECTIVES: To describe and analyze how Brazilian psychiatrists

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

    Science.gov (United States)

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

    2017-11-21

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

  4. Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

    International Nuclear Information System (INIS)

    Li, Su; Wang, Anxun; Jiang, Wenqi; Guan, Zhongzhen

    2008-01-01

    It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(γ-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t 1/2 , 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L), and greater distribution volume (V D , 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05). In our

  5. Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

    Directory of Open Access Journals (Sweden)

    Jiang Wenqi

    2008-04-01

    Full Text Available Abstract Background It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU loaded block copolymers, with poly(γ-benzyl-L-glutamate (PBLG as the hydrophobic block and poly(ethylene glycol (PEG as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. Methods 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM and transmission electron microscopy (TEM were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC. To study in vivo effects, LoVo cells (human colon cancer cell line or Tca8113 cells (human oral squamous cell carcinoma cell line were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. Results 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min, lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L, and greater distribution volume (VD, 0.114 L vs. 0.069 L. Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p 0.05. Conclusion In our model system, 5-FU/PEG-PBLG nanoparticles

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

    Science.gov (United States)

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

    2017-10-15

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

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

    Science.gov (United States)

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

    2013-01-01

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

  8. Encapsulation of anticancer drug and magnetic particles in biodegradable polymer nanospheres

    Energy Technology Data Exchange (ETDEWEB)

    Koneracka, M; Zavisova, V; Tomasovicova, N; Kopcansky, P; Timko, M; JurIkova, A; Csach, K; Kavecansky, V; Lancz, G [Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, Kosice (Slovakia); Muckova, M [Hameln rds a.s., Horna 36, Modra (Slovakia)], E-mail: konerack@saske.sk

    2008-05-21

    In this study, we have prepared PLGA (poly-D,L-lactide-co-glycolide) nanospheres loaded with biocompatible magnetic fluid and anticancer drug taxol by a modified nanoprecipitation technique and investigated their magnetic properties. A magnetic fluid, MF-PEG, with a biocompatible layer of polyethylene glycol (PEG), was chosen as a magnetic carrier. The PLGA, whose copolymer ratio of D,L-lactide to glycolide is 85:15, was utilized as a capsulation material. Taxol, as an important anticancer drug, was chosen for its significant role against a wide range of tumours. The morphology and particle size distributions of the prepared nanospheres were investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and showed a spherical shape of prepared nanospheres with size 250 nm. Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetry (TGA) analysis confirmed incorporation of magnetic particles and taxol into the PLGA polymer. The results showed good encapsulation with magnetite content 21.5 wt% and taxol 0.5 wt%. Magnetic properties of magnetic fluids and taxol within the PLGA polymer matrix were investigated by SQUID magnetometry from 4.2 to 300 K. The SQUID measurements showed superparamagnetism of prepared nanospheres with a blocking temperature of 160 K and saturation magnetization 1.4 mT.

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

    Science.gov (United States)

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

    2016-08-25

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

  10. Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.

    Science.gov (United States)

    Chen, Rui; Xu, Liu; Fan, Qin; Li, Man; Wang, Jingjing; Wu, Li; Li, Weidong; Duan, Jinao; Chen, Zhipeng

    2017-11-01

    Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC-MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.

  11. The effect of near-infrared fluorescence conjugation on the anti-cancer potential of cetuximab.

    Science.gov (United States)

    Yun, Ji Young; Hyun, Byung-Hwa; Nam, Sang Yoon; Yun, Young Won; Lee, Hu-Jang; Lee, Beom-Jun

    2018-03-01

    This study investigated the anti-cancer potential of a near-infrared fluorescence (NIRF) molecule conjugated with Cetuximab (Cetuximab-NIRF) in six-week-old female BALB/c athymic (nu+/nu+) nude mice. A431 cells were cultured and injected into the animals to induce solid tumors. Paclitaxel (30 mg/kg body weight (BW)), Cetuximab (1 mg/kg BW), and Cetuximab-NIRF (0.25, 0.5 and 1.0 mg/kg BW) were intraperitoneally injected twice a week into the A431 cell xenografts of the nude mice. Changes in BW, tumor volume and weight, fat and lean mass, and diameter of the peri-tumoral blood vessel were determined after two weeks. Tumor volumes and weights were significantly decreased in the Cetuximab-NIRF (1 mg/kg BW) group compared with the control group ( P <0.001). Lean mass and total body water content were also conspicuously reduced in the Cetuximab-NIRF (1 mg/kg BW) group compared with the vehicle control group. Peri-tumoral blood vessel diameters were very thin in the Cetuximab-NIRF groups compared with those of the paclitaxel group. These results indicate that the conjugation of Cetuximab with NIRF does not affect the anti-cancer potential of Cetuximab and NIRF can be used for molecular imaging in cancer treatments.

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

    Science.gov (United States)

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

    2015-10-30

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

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

    Directory of Open Access Journals (Sweden)

    Emma M Brown

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

  14. Carbohydrate-based heteronuclear complexes as topoisomerase Iα inhibitor: approach toward anticancer chemotherapeutics.

    Science.gov (United States)

    Afzal, Mohd; Al-Lohedan, Hamad A; Usman, Mohammad; Tabassum, Sartaj

    2018-04-18

    Due to the critical role of cellular enzymes necessary for cell proliferation by deciphering topological hurdles in the process of DNA replication, topoisomerases have been one of the major targets in the anticancer drug development area. A need, therefore, arises for new metallodrugs that specifically recognizes DNA and inhibits the activity of topoisomerase enzymes, herein, we report the synthesis and characterization of new metal-based glycoconjugate entities containing heterobimetallic core Cu II -Sn IV (1) and Ni II -Sn IV (2) derived from N-glycoside ligand (L). The optimized structure of complex 1 and other significant vibrational modes have been explained using dispersion corrected B3LYP/DFT calculations. In vitro DNA binding profile of the L and both the complexes 1 and 2 were done by various biophysical studies. Complex 1 breaks pBR322 DNA via a hydrolytic means which was validated by T4 DNA enzymatic assay. To get a mechanistic insight of mode of action topoisomerase I (Topo I) inhibition assay was carried out. Also, we have taken the help of molecular modeling studies in accordance with experimental findings. In vitro cytotoxicity of the complex 1 was evaluated against a panel of cancer cells which exhibited remarkably good anticancer activity (GI 50 values <10 μg/ml). Moreover, intracellular localization of the complex 1 was visualized by confocal microscopy against HeLa cells.

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

    Directory of Open Access Journals (Sweden)

    Amita Mishra

    2013-01-01

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

  16. Synthesis, SAR and pharmacological characterization of novel anthraquinone cation compounds as potential anticancer agents.

    Science.gov (United States)

    Zheng, Yanyan; Zhu, Li; Fan, Lulu; Zhao, Wenna; Wang, Jianlong; Hao, Xianxiao; Zhu, Yunhui; Hu, Xiufang; Yuan, Yaofeng; Shao, Jingwei; Wang, Wenfeng

    2017-01-05

    Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been demonstrated to exhibit good anti-cancer effect. In this study, a series of novel quaternary ammonium salts of emodin, anthraquinone and anthrone were synthesized and their anticancer activities were tested in vitro. The effects of emodin quaternary ammonium salts on cell viability, apoptosis, intracellular ROS, and mitochondrial membrane potential were investigated in A375, BGC-823, HepG2 and HELF cells. The results demonstrated that compound 4a induced morphological changes and decreased cell viability. Apoptosis triggered by compound 4a was visualized using DAPI staining and Annexin V-FITC/PI staining. Compound 4a-induced apoptosis of A375 cells were showed to be associated with the dissipation of mitochondrial membrane potential (ΔΨm) as a result of the up-regulation of P53 and Caspase-3. When cancer cells were treated with emodin derivative, their ability to generate reactive oxygen species (ROS) rose significantly and the mitochondrial membrane potential decreased. Additionally, confocal microscopy assay confirmed that compound 4a was primarily located in the mitochondria of A375 cells. These results suggested that compound 4a has the potential for use in cancer therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Assessment of Olea europaea L. fruit extracts: Phytochemical characterization and anticancer pathway investigation.

    Science.gov (United States)

    Maalej, Amina; Bouallagui, Zouhaier; Hadrich, Fatma; Isoda, Hiroko; Sayadi, Sami

    2017-06-01

    Olea europaea L. has been widely used as an advantageous rich source of bioactive compounds of high economic value leading to its use in pharmaceutical, cosmetic, and agriculture industries. Ethanolic extracts of olive fruits from three different cultivars (OFE) were studied for their phytochemical contents and were investigated for antioxidant activities and anticancer potential. Major polyphenols detected in these extracts were tyrosol, hydroxytyrosol, oleuropein, rutin, quercetin and glucoside forms of luteolin and apigenin. All these compounds have shown to significantly contribute to the antioxidant activity of OFE, which was evaluated by DPPH and ABTS assays. Proliferation of hepatic and colon cancer cells, HepG2 and Caco-2, were shown to be sensitive to OFE with IC 50 less than 1.6mg/ml for all tested extracts. Moreover, flow cytometry analysis showed that OFE induced cell cycle arrest in the S-phase within both HepG2 and Caco-2 cells. This has triggered a cell death mechanism as shown by DNA fragmentation, expression of p53 and phosphorylation level of Akt and Erk proteins. Interestingly, these extracts could be further used as a potential source of natural compounds with both antioxidant and anticancer effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Covalent Organic Framework Material bearing Phloroglucinol Building Units as a Potent Anticancer Agent

    KAUST Repository

    Bhanja, Piyali; Mishra, Snehasis; Manna, Krishnendu; Mallick, Arijit; Das Saha, Krishna; Bhaumik, Asim

    2017-01-01

    Covalent organic frameworks (COFs) having periodicity in pores of nanoscale dimensions can be suitably designed for the organic building units bearing reactive functional groups at their surfaces. Thus, they are an attractive option as an anticancer agent to overcome the limitations of chemotherapy. Herein, we first report a new porous biodegradable nitrogen containing COF material, EDTFP-1 (ethylenedianiline-triformyl phloroglucinol), synthesized using 4,4'-ethylenedianiline and 2,4,6-triformylphloroglucinol via Schiff base condensation reaction. EDTFP-1 exhibited 3D-hexagonal porous structure with average pores of ca. 1.5 nm dimension. Here, we have explored the anti-cancer potentiality of EDTFP-1. Result demonstrated an enhanced cytotoxicity was observed against four cancer cells HCT 116, HepG2, A549, and MIA-Paca2 with significant lower IC50 on HCT116 cells. Additionally, EDTFP-1-induced cell death was associated with the characteristic apoptotic changes like cell membrane blebbing, nuclear DNA fragmentation, externalization of phosphatidylserine from the cell membrane followed by a loss of mitochondrial membrane potential as well as modulation of pro and anti-apoptotic proteins. Further, the result depicted a direct correlation between the generations of ROS with mitochondrial-dependant apoptosis through the involvement of p53 phosphorylation upon EDTFP-1 induction, suggesting this COF material is a novel chemotherapeutic agent for cancer treatment.

  19. Covalent Organic Framework Material bearing Phloroglucinol Building Units as a Potent Anticancer Agent

    KAUST Repository

    Bhanja, Piyali

    2017-08-23

    Covalent organic frameworks (COFs) having periodicity in pores of nanoscale dimensions can be suitably designed for the organic building units bearing reactive functional groups at their surfaces. Thus, they are an attractive option as an anticancer agent to overcome the limitations of chemotherapy. Herein, we first report a new porous biodegradable nitrogen containing COF material, EDTFP-1 (ethylenedianiline-triformyl phloroglucinol), synthesized using 4,4\\'-ethylenedianiline and 2,4,6-triformylphloroglucinol via Schiff base condensation reaction. EDTFP-1 exhibited 3D-hexagonal porous structure with average pores of ca. 1.5 nm dimension. Here, we have explored the anti-cancer potentiality of EDTFP-1. Result demonstrated an enhanced cytotoxicity was observed against four cancer cells HCT 116, HepG2, A549, and MIA-Paca2 with significant lower IC50 on HCT116 cells. Additionally, EDTFP-1-induced cell death was associated with the characteristic apoptotic changes like cell membrane blebbing, nuclear DNA fragmentation, externalization of phosphatidylserine from the cell membrane followed by a loss of mitochondrial membrane potential as well as modulation of pro and anti-apoptotic proteins. Further, the result depicted a direct correlation between the generations of ROS with mitochondrial-dependant apoptosis through the involvement of p53 phosphorylation upon EDTFP-1 induction, suggesting this COF material is a novel chemotherapeutic agent for cancer treatment.

  20. Co-possession of phosphodiesterase type-5 inhibitors (PDE5-I) with nitrates.

    Science.gov (United States)

    Chang, Li-Ling; Ma, Mark; Allmen, Heather von; Henderson, Scott C; Harper, Kristine; Hornbuckle, Kenneth

    2010-06-01

    Estimate the proportion of phosphodiesterase type-5 inhibitor (PDE5-I) patients who co-possess nitrates and compare the proportion of tadalafil patients dispensed nitrates to a matched control group. Secondarily, examine the percentage of co-possession of PDE5-Is and nitrates where the products were dispensed on the same day or written by the same prescriber. Male patients aged 18+ years filling PDE5-I prescriptions between December 2003 and March 2006 were identified using a U.S. longitudinal prescription database (IMS Health LRx). Similar patients not dispensed a PDE5-I during this period were matched to the tadalafil-dispensed cohort using a propensity score approach. Co-possession, as a proxy for concurrent use, was defined as an overlap in time on therapy for a PDE5-I and nitrate and was compared for the three PDE5-Is and for tadalafil to the matched control group. Among 601,063 tadalafil patients, 3.31% were dispensed a nitrate during the study period, compared to 6.18% in control patients (n = 601,063). When co-possessed prescriptions were defined by overlapping exposure periods, the proportion of PDE5-I patients with co-possessed nitrates ranged from 1.44% (tadalafil) to 1.72% (vardenafil) and 2.13% (sildenafil). Co-possession percentages of PDE5-I prescriptions were 0.83% for tadalafil and 1.07% for sildenafil and vardenafil. The majority (54.29%) of co-possessed PDE5-I and nitrate prescriptions had the nitrate dispensed prior to the PDE5-I prescription identified in the study cohort. Keeping in mind the limitations of observational studies, these results suggest that co-dispensing of nitrates and PDE5-Is is low. Compared to control patients, the proportion of nitrate co-possession was lowest for patients filling tadalafil. Tadalafil patients also had the lowest co-possessed proportion among the three PDE5-I cohorts. While the majority of co-possessed drug pairs were prescribed by different providers, the highest percentage of co-prescribing from the same

  1. Rheum turkestanicum rhizomes possess anti-hypertriglyceridemic, but not hypoglycemic or hepatoprotective effect in experimental diabetes

    Directory of Open Access Journals (Sweden)

    Mousa-Al-Reza Hadjzadeh

    2017-01-01

    Full Text Available Objective: Rheum turkestanicum (R. turkestanicum rhizomes have been used in Iranain traditional medicine as an anti-diabetic agent. The purpose of the present investigation was to evaluate the anti-diabetic and antioxidant activities of R. turkestanicum rhizome extract in streptozotocin-induced diabetic rats.Materials and Methods: Diabetes was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin in male Wistar rats. Diabetic rats received the decoction extract of R. turkestanicum rhizomes at the doses of 200, 400 and 600 mg/kg daily by gavage for 3 weeks. Serum glucose and lipid levels were measured in all groups before diabetes induction and at the end of week 3. Oxidative stress was evaluated in the liver by measurement of malondialdehyde levels and total thiol concentration at the end of the experiment.Results: A significant increase in serum glucose and triglyceride levels was observed in diabetic rats, which was accompanied by increased malondialdehyde levels and decreased total thiol concentration in the liver after 3 weeks. Treatment of diabetic rats with R. turkestanicum rhizome extract at the doses of 200, 400 and 600 mg/kg over a 3-week period did not change serum glucose, hepatic malondialdehyde and total thiol levels in diabetic rats. However, treatment with R. turkestanicum extract significantly decreased serum triglyceride levels in a dose-dependent manner at the end of the experiment.Conclusion: R. turkestanicum rhizome extract possess anti-hypertriglyceridemic, but not hypoglycemic or hepatoprotective effect in diabetic rats. Therefore, R. turkestanicum rhizome should be consumed with more caution by diabetic patients.

  2. Anticancer effect of a Kampo preparation Daikenchuto.

    Science.gov (United States)

    Nagata, Takuya; Toume, Kazufumi; Long, Lv Xiao; Hirano, Katsuhisa; Watanabe, Toru; Sekine, Shinichi; Okumura, Tomoyuki; Komatsu, Katsuko; Tsukada, Kazuhiro

    2016-07-01

    No traditional Japanese and Chinese herbal preparations have been shown to be effective antitumor agents, and a Japanese herbal therapy (Kampo medicine) for cancer that causes fewer adverse drug reactions than orthodox pharmaceuticals is desired. Our present study demonstrated that a Kampo preparation Daikenchuto (DKT) exerts an antitumor effect against various cancer cells. We also discovered an antitumor factor in Japanese Zanthoxylum peel, which is an ingredient of DKT. Breast, esophageal, gastric, and colon cancer cell lines were individually incubated with DKT for 1-72 h, followed by assessment of tumor growth inhibition by MTT assay. The cancer cells were also analyzed for apoptotic changes after DKT treatment. Nude mice were used to establish a model of gastric cancer tumor growth and peritoneal disseminated metastasis, in which the number of peritoneal disseminations was evaluated after oral administration of DKT for 4 weeks. In addition, the antitumor effects of the individual DKT ingredients (viz., ginseng, Japanese Zanthoxylum peel, and processed ginger) and other Kampo preparations were also analyzed. The antitumor effect of DKT was demonstrated in gastric, breast, esophageal, and colon cancer cells. DKT treatment induced apoptosis in these cells. Oral administration of DKT had a tendency to reduce the growth and significantly reduced the peritoneal dissemination of gastric cancer in the nude mouse model compared with control. DKT exhibited a higher antitumor effect than other Kampo preparations. Furthermore, Japanese Zanthoxylum peel, an ingredient of DKT, showed a particularly potent antitumor effect. Our study indicated that DKT is useful as a Kampo preparation for cancer therapy. We also showed that Japanese Zanthoxylum peel, an ingredient of DKT, contains an antitumor factor.

  3. Moral significance of phenomenal consciousness.

    Science.gov (United States)

    Levy, Neil; Savulescu, Julian

    2009-01-01

    Recent work in neuroimaging suggests that some patients diagnosed as being in the persistent vegetative state are actually conscious. In this paper, we critically examine this new evidence. We argue that though it remains open to alternative interpretations, it strongly suggests the presence of consciousness in some patients. However, we argue that its ethical significance is less than many people seem to think. There are several different kinds of consciousness, and though all kinds of consciousness have some ethical significance, different kinds underwrite different kinds of moral value. Demonstrating that patients have phenomenal consciousness--conscious states with some kind of qualitative feel to them--shows that they are moral patients, whose welfare must be taken into consideration. But only if they are subjects of a sophisticated kind of access consciousness--where access consciousness entails global availability of information to cognitive systems--are they persons, in the technical sense of the word employed by philosophers. In this sense, being a person is having the full moral status of ordinary human beings. We call for further research which might settle whether patients who manifest signs of consciousness possess the sophisticated kind of access consciousness required for personhood.

  4. Investigations into the Mechanisms of Cell Death: The Common Link between Anticancer Nanotherapeutics and Nanotoxicology

    Science.gov (United States)

    Minocha, Shalini

    Nanotoxicology and anticancer nanotherapeutics are essentially two sides of the same coin. The nanotoxicology discipline deals with the nanoparticle (NP)-induced toxicity and mechanisms of cell death in healthy cells, whereas anticancer agents delivered via nano-based approaches aim to induce cell death in abnormally proliferating cancer cells. The objectives of the studies presented herein were two-fold; to (a) systematically study the physico-chemical properties and cell death mechanisms of model NPs and (b) utilize the knowledge gained from cell death-nanotoxicity studies in developing a potentially novel anticancer nanotherapeutic agent. For the first objective, the effect of a distinguishing characteristic, i.e., surface carbon coating on the matched pairs of carbon-coated and non-coated copper and nickel NPs (Cu, C-Cu, Ni and C-Ni) on the physico-chemical properties and toxicity in A549 alveolar epithelial cells were evaluated. The effect of carbon coating on particle size, zeta potential, oxidation state, cellular uptake, release of soluble metal and concentration dependent toxicity of Cu and Ni NPs was systematically evaluated. A significant effect of carbon coating was observed on the physico-chemical properties, interaction with cellular membranes, and overall toxicity of the NPs. C-Cu NPs, compared to Cu NPs, showed four-fold lower release of soluble copper, ten-fold higher cellular uptake and protection against surface oxidation. In toxicity assays, C-Cu NPs induced higher mitochondrial damage than Cu NPs whereas Cu NPs were associated with a significant damage to plasma membrane integrity. Nickel and carbon coated nickel NPs were less toxic compared to Cu and C-Cu NPs. Thus, by studying the effect of carbon coating, correlations between physico-chemical properties and toxicity of NPs were established. The second objective was focused on utilizing nano-based approaches for the intracellular delivery of an anticancer agent, Cytochrome c (Cyt c), to

  5. [Different effects of anticancer drugs on two human thyroid cell lines with different stages of differentiation].

    Science.gov (United States)

    Yamanaka, T; Hishinuma, A

    1995-01-20

    We established two human thyroid tumor cell lines. One cell line (hPTC) was established from the tissue of a papillary thyroid carcinoma surgically excised from a 27-year-old female patient. The other cell line (hAG) was established from the tissue of an adenomatous goiter excised from a 59-year old female patient. Synthesis of cAMP by hPTC and hAG increased when they were stimulated by TSH. hPTC and hAG continued to divide as a monolayer in a tissue culture for three years and two years, respectively. We assessed the efficacy of anticancer drugs (doxorubicin:ADR, cisplatin:CDDP, nimustine:ACNU, bleomycin:BLM, cyclophosphamide:CPA, aclarubicin:ACR) with resard to hPTC. The hPTC cells were cultured in 24-well plates in the presence of the anticancer drugs for 48 hours, and the cellular DNA of the live cells was measured with diaminobenzoic acid. ADR had the lowest ED50 (0.029 mu g/ml) and the clinical blood concentration was 13.8 times that of the ED50. The clinical blood concentration divided by ED50 for the other anticancer drugs are, in order of higher values, 2.3 for CPA, 1.7 for BLM, 1.2 for CDDP, 0.5 for ACR, and less than 0.1 for ACNU. ADR showed time-independent effects since a 2-hour exposure of ADR to the hPTC cells resulted in the significant reduction of the cellular DNA content of the live cells even after 48 hours. The effects of the other anticancer drugs were time-dependent. We then studied the difference of the effects of ADR on hPTC and hAG. ED50 for hPTC was significantly low (0.035 mu g/ml) compared to that for hAG (0.460 mu g/ml). Since free radical formation is one of the major anticancer mechanisms of ADR the effects of free radicals on ED50's for hPTC and hAG were measured by adding glutathione (GSH), N-acetylcystein (NAC), buthionine sulfoximine (BSO), and alpha-tocopherol (alpha-toco) into the culture media. GSH catches up with free radicals in the extracellular fluid. NAC promotes production of GSH in the cytoplasm, but BSO interferes with

  6. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

    Directory of Open Access Journals (Sweden)

    Daniel René

    2008-05-01

    Full Text Available Abstract The acquired immunodeficiency syndrome (AIDS is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis. This review focuses on newly discovered connections of the HIV-1 protein Tat, as well as cellular co-factors of Tat, to double-strand break DNA repair. We propose that the Tat-induced DNA repair deficiencies may play a significant role in the development of AIDS-associated cancer.

  8. Synthesis and characterization of 2-substituted benzimidazoles and their evaluation as anticancer agent

    Science.gov (United States)

    Azam, Mohammad; Khan, Azmat Ali; Al-Resayes, Saud I.; Islam, Mohammad Shahidul; Saxena, Ajit Kumar; Dwivedi, Sourabh; Musarrat, Javed; Trzesowska-Kruszynska, Agata; Kruszynski, Rafal

    2015-05-01

    In this work, we report a series of benzimidazole derivatives synthesized from benzene-1,2-diamine and aryl-aldehydes at room temperature. The synthesized compounds have been characterized on the basis of elemental analysis and various spectroscopic studies viz., IR, 1H- and 13C-NMR, ESI-MS as well by X-ray single X-ray crystallographic study. Interaction of these compounds with CT-DNA has been examined with fluorescence experiments and showed significant binding ability. All the synthesized compounds have been screened for their antitumor activities against various human cancer cell lines viz., Human breast adenocarcinoma cell line (MCF-7), Human leukemia cell line (THP-1), Human prostate cancer cell lines (PC-3) and adenocarcinomic human alveolar basal epithelial cell lines (A-549). Interestingly, all the compounds showed significant anticancer activity.

  9. Investigating the Impact of Possession-Way of a Smartphone on Action Recognition

    Directory of Open Access Journals (Sweden)

    Zae Myung Kim

    2016-06-01

    Full Text Available For the past few decades, action recognition has been attracting many researchers due to its wide use in a variety of applications. Especially with the increasing number of smartphone users, many studies have been conducted using sensors within a smartphone. However, a lot of these studies assume that the users carry the device in specific ways such as by hand, in a pocket, in a bag, etc. This paper investigates the impact of providing an action recognition system with the information of the possession-way of a smartphone, and vice versa. The experimental dataset consists of five possession-ways (hand, backpack, upper-pocket, lower-pocket, and shoulder-bag and two actions (walking and running gathered by seven users separately. Various machine learning models including recurrent neural network architectures are employed to explore the relationship between the action recognition and the possession-way recognition. The experimental results show that the assumption of possession-ways of smartphones do affect the performance of action recognition, and vice versa. The results also reveal that a good performance is achieved when both actions and possession-ways are recognized simultaneously.

  10. Gun possession among American youth: a discovery-based approach to understand gun violence.

    Science.gov (United States)

    Ruggles, Kelly V; Rajan, Sonali

    2014-01-01

    To apply discovery-based computational methods to nationally representative data from the Centers for Disease Control and Preventions' Youth Risk Behavior Surveillance System to better understand and visualize the behavioral factors associated with gun possession among adolescent youth. Our study uncovered the multidimensional nature of gun possession across nearly five million unique data points over a ten year period (2001-2011). Specifically, we automated odds ratio calculations for 55 risk behaviors to assemble a comprehensive table of associations for every behavior combination. Downstream analyses included the hierarchical clustering of risk behaviors based on their association "fingerprint" to 1) visualize and assess which behaviors frequently co-occur and 2) evaluate which risk behaviors are consistently found to be associated with gun possession. From these analyses, we identified more than 40 behavioral factors, including heroin use, using snuff on school property, having been injured in a fight, and having been a victim of sexual violence, that have and continue to be strongly associated with gun possession. Additionally, we identified six behavioral clusters based on association similarities: 1) physical activity and nutrition; 2) disordered eating, suicide and sexual violence; 3) weapon carrying and physical safety; 4) alcohol, marijuana and cigarette use; 5) drug use on school property and 6) overall drug use. Use of computational methodologies identified multiple risk behaviors, beyond more commonly discussed indicators of poor mental health, that are associated with gun possession among youth. Implications for prevention efforts and future interdisciplinary work applying computational methods to behavioral science data are described.

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

    Directory of Open Access Journals (Sweden)

    Myoung Lae Cho

    2010-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Joan Crous-Masó

    2018-05-01

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

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

    Science.gov (United States)

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

    2018-05-11

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

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

    Directory of Open Access Journals (Sweden)

    Baskaran R

    2014-06-01

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

  15. Anti-Cancer Effects of Imperata cylindrica Leaf Extract on Human Oral Squamous Carcinoma Cell Line SCC-9 in Vitro.

    Science.gov (United States)

    Keshava, Rohini; Muniyappa, Nagesh; Gope, Rajalakshmi; Ramaswamaiah, Ananthanarayana Saligrama

    2016-01-01

    Imperata cylindrica, a tall tufted grass which has multiple pharmacological applications is one of the key ingredients in various traditional medicinal formula used in India. Previous reports have shown that I. cylindrica plant extract inhibited cell proliferation and induced apoptosis in various cancer cell lines. To our knowledge, no studies have been published on the effect of I. cylindrica leaf extract on human oral cancers. The present study was undertaken in order to evaluate the anticancer properties of the leaf extract of I. cylindrica using an oral squamous cell carcinoma cell line SCC-9 as an in vitro model system. A methanol extract from dried leaves of I. cylindrica (ICL) was prepared by standard procedures. Effects of the ICL extract on the morphology of SCC-9 cells was visualized by microscopy. Cytotoxicity was determined by MTT assay. Effects of the ICL extract on colony forming ability of SCC-9 cells was evaluated using clonogenic assay. Cell cycle analysis was performed by flow cytometry and induction of apoptosis was determined by DNA fragmentation assay. The ICL extract treatment caused cytotoxicity and induced cell death in vitro in SCC-9 cells in a dose-dependent manner. This treatment also significantly reduced the clonogenic potential and inhibited cell proliferation by arresting the cell cycle in the G2/M phase. Furthermore, DNA fragmentation assays showed that the observed cell death was caused by apoptosis. This is the first report showing the anticancer activity of the methanol extracts from the leaves of I. cylindrica in human oral cancer cell line. Our data indicates that ICL extract could be considered as one of the lead compounds for the formulation of anticancer therapeutic agents to treat/manage human oral cancers. The natural abundance of I. cylindrica and its wide geographic distribution could render it one of the primary resource materials for preparation of anticancer therapeutic agents.

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

    OpenAIRE

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chi H.J. Kao

    2013-02-01

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

  18. Slow angled-descent forepaw grasping (SLAG): an innate behavioral task for identification of individual experimental mice possessing functional vision.

    Science.gov (United States)

    Gil-Pagés, Macarena; Stiles, Robert J; Parks, Christopher A; Neier, Steven C; Radulovic, Maja; Oliveros, Alfredo; Ferrer, Alejandro; Reed, Brendan K; Wilton, Katelynn M; Schrum, Adam G

    2013-08-23

    There is significant interest in the generation of improved assays to clearly identify experimental mice possessing functional vision, a property that could qualify mice for inclusion in behavioral and neuroscience studies. Widely employed current methods rely on mouse responses to visual cues in assays of reflexes, depth perception, or cognitive memory. However, commonly assessed mouse reflexes can sometimes be ambiguous in their expression, while depth perception assays are sometimes confounded by variation in anxiety responses and exploratory conduct. Furthermore, in situations where experimental groups vary in their cognitive memory capacity, memory assays may not be ideal for assessing differences in vision. We have optimized a non-invasive behavioral assay that relies on an untrained, innate response to identify individual experimental mice possessing functional vision: slow angled-descent forepaw grasping (SLAG). First, we verified that SLAG performance depends on vision and not olfaction. Next, all members of an age-ranged cohort of 158 C57BL/6 mice (57 wild-type, 101 knockout, age range 44-241 days) were assessed for functional vision using the SLAG test without training or conditioning. Subjecting the population to a second innate behavioral test, Dark Chamber preference, corroborated that the functional vision assessment of SLAG was valid. We propose that the SLAG assay is immediately useful to quickly and clearly identify experimental mice possessing functional vision. SLAG is based on a behavioral readout with a significant innate component with no requirement for training. This will facilitate the selection of mice of known sighted status in vision-dependent experiments that focus on other types of behavior, neuroscience, and/or cognitive memory.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  20. Demonic possessions and mental illness: discussion of selected cases in late medieval hagiographical literature.

    Science.gov (United States)

    Espí Forcén, Carlos; Espí Forcén, Fernando

    2014-01-01

    During the Middle Ages, demonic possession constituted an explanation for an erratic behavior in society. Exorcism was the treatment generally applied to demoniacs and seems to have caused some alleviation in the suffering of mentally distressed people. We have selected and analyzed some cases of demonic possession from thirteenth-century hagiographical literature. In the description of demoniacs we have been able to find traits of psychotic, mood, neurotic, personality disorders and epilepsy. The exorcisms analyzed in our article are the result of literary invention more than the description of a contemporary event. Nevertheless, the writers were witnesses of their time, transferred their knowledge about exorcism and possession in their narrative and presumably incorporated their actual experience with demoniacs.

  1. Prepositions in Use: Prepositions of Standard, Prepositions of Possession and Prepositions of Accompaniment

    Directory of Open Access Journals (Sweden)

    Naji Masned AlQbailat

    2016-08-01

    Full Text Available The current research paper attempted at investigating the use of prepositions of standard, prepositions of possession and prepositions of accompaniment by some Jordanian learners of English. A total of 53 Jordanian English Majors participated in the study from the department of English language at Princess Alia University College. In collecting the needed data for the purpose of the study, the researchers employed fifteen items of a multiple choice test. The results of the study showed that Jordanian learners of English encountered moderate difficulty in learning the three aforesaid usages of prepositions. This difficulty is ascribed mainly to first language interference more than intralingual interference. It was also found that prepositions of standard are the most difficult to learn by the participants, followed by prepositions of accompaniment and prepositions of possession respectively.       Keywords: First language Interference, Intralingual Interference, Prepositions of Standard, Prepositions of Accompaniment, Prepositions of Possession

  2. Does possession of assets increase women's participation in reproductive decision-making? Perceptions of Nigerian women.

    Science.gov (United States)

    Omeje, Joachim C; Oshi, Sarah N; Oshi, Daniel C

    2011-01-01

    This study is based on a population-based, descriptive questionnaire survey, the objective of which was to elicit the perceptions of women in south-eastern Nigeria on whether possession of economic/household assets by women enhanced their capacity to negotiate reproductive issues with their husbands. The findings show that the respondents believed that possession of economic/household assets by women in their communities might not necessarily increase their negotiation power in their reproductive decision-making. Other factors tend to attenuate the effects of women's possession of economic/household assets on their reproductive bargaining power. Notable among these may be social norms that implicitly arrogate control of the assets owned by the conjugal couple to the man, even when they are bought by the women. Planners of reproductive health intervention projects, policy-makers and researchers need to be aware of such sociocultural specific phenomena, which do not fit with widely held international beliefs.

  3. Novel rod-shaped viruses isolated from garlic, Allium sativum, possessing a unique genome organization.

    Science.gov (United States)

    Sumi, S; Tsuneyoshi, T; Furutani, H

    1993-09-01

    Rod-shaped flexuous viruses were partially purified from garlic plants (Allium sativum) showing typical mosaic symptoms. The genome was shown to be composed of RNA with a poly(A) tail of an estimated size of 10 kb as shown by denaturing agarose gel electrophoresis. We constructed cDNA libraries and screened four independent clones, which were designated GV-A, GV-B, GV-C and GV-D, using Northern and Southern blot hybridization. Nucleotide sequence determination of the cDNAs, two of which correspond to nearly one-third of the virus genomic RNA, shows that all of these viruses possess an identical genomic structure and that also at least four proteins are encoded in the viral cDNA, their M(r)s being estimated to be 15K, 27K, 40K and 11K. The 15K open reading frame (ORF) encodes the core-like sequence of a zinc finger protein preceded by a cluster of basic amino acid residues. The 27K ORF probably encodes the viral coat protein (CP), based on both the existence of some conserved sequences observed in many other rod-shaped or flexuous virus CPs and an overall amino acid sequence similarity to potexvirus and carlavirus CPs. The 11K ORF shows significant amino acid sequence similarities to the corresponding 12K proteins of the potexviruses and carlaviruses. On the other hand, the 40K ORF product does not resemble any other plant virus gene products reported so far. The genomic organization in the 3' region of the garlic viruses resembles, but clearly differs from, that of carlaviruses. Phylogenetic analysis based upon the amino acid sequence of the viral capsid protein also indicates that the garlic viruses have a unique and distinct domain different from those of the potexvirus and carlavirus groups. The results suggest that the garlic viruses described here belong to an unclassified and new virus group closely related to the carlaviruses.

  4. Exosomes carring gag/env of ALV-J possess negative effect on immunocytes.

    Science.gov (United States)

    Wang, Guihua; Wang, Zhenzhen; Zhuang, Pingping; Zhao, Xiaomin; Cheng, Ziqiang

    2017-11-01

    J subgroup avian leukosis virus (ALV-J) is an exogenous retrovirus of avian. A key feature of ALV-J infection is leading to severe immunosuppressive characteristic of diseases. Viral components of retrovirus were reported closely associated with immunosuppression, and several similarities between exosomes and retrovirus preparations have lead to the hypotheses of retrovirus hijacker exosomes pathway. In this study, we purified exosomes from DF-1 cells infected and uninfected by ALV-J. Electron microscopy and mass spectrometry (MS) analysis showed that ALV-J not only increased the production of exosomes from ALV-J infected DF-1 cells (Exo-J) but also stimulated some proteins expression, especially ALV-J components secreted in exosomes. Immunosuppressive domain peptide (ISD) of envelope subunit transmembrane (TM) and gag of ALV-J were secreted in Exo-J. It has been reported that HIV gag was budded from endosome-like domains of the T cell plasma membrane. But env protein was first detected in exosomes from retrovirus infected cells. We found that Exo-J caused negative effects on splenocytes in a dose-dependant manner by flow cytometric analysis. And low dose of Exo-J activated immune activity of splenocytes, while high dose possessed immunosuppressive properties. Interestingly, Exo-J has no significant effects on the immunosuppression induced by ALV-J, and the immunosuppressive effects induced by Exo-J lower than that by ALV-J. Taken together, our data indicated that Exo-J supplied a microenvironment for the replication and transformation of ALV-J. Copyright © 2017. Published by Elsevier Ltd.

  5. Mycobacterium avium Possesses Extracellular DNA that Contributes to Biofilm Formation, Structural Integrity, and Tolerance to Antibiotics.

    Directory of Open Access Journals (Sweden)

    Sasha J Rose

    Full Text Available Mycobacterium avium subsp. hominissuis is an opportunistic pathogen that is associated with biofilm-related infections of the respiratory tract and is difficult to treat. In recent years, extracellular DNA (eDNA has been found to be a major component of bacterial biofilms, including many pathogens involved in biofilm-associated infections. To date, eDNA has not been described as a component of mycobacterial biofilms. In this study, we identified and characterized eDNA in a high biofilm-producing strain of Mycobacterium avium subsp. hominissuis (MAH. In addition, we surveyed for presence of eDNA in various MAH strains and other nontuberculous mycobacteria. Biofilms of MAH A5 (high biofilm-producing strain and MAH 104 (reference strain were established at 22°C and 37°C on abiotic surfaces. Acellular biofilm matrix and supernatant from MAH A5 7 day-old biofilms both possess abundant eDNA, however very little eDNA was found in MAH 104 biofilms. A survey of MAH clinical isolates and other clinically relevant nontuberculous mycobacterial species revealed many species and strains that also produce eDNA. RAPD analysis demonstrated that eDNA resembles genomic DNA. Treatment with DNase I reduced the biomass of MAH A5 biofilms when added upon biofilm formation or to an already established biofilm both on abiotic surfaces and on top of human pharyngeal epithelial cells. Furthermore, co-treatment of an established biofilm with DNase 1 and either moxifloxacin or clarithromycin significantly increased the susceptibility of the bacteria within the biofilm to these clinically used antimicrobials. Collectively, our results describe an additional matrix component of mycobacterial biofilms and a potential new target to help treat biofilm-associated nontuberculous mycobacterial infections.

  6. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  7. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-01

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

  8. Enhanced anticancer effects of Scutellaria barbata D. Don in combination with traditional Chinese medicine components on non-small cell lung cancer cells.

    Science.gov (United States)

    Wang, Qian; Acharya, Narayan; Liu, Zhongwei; Zhou, Xianmei; Cromie, Meghan; Zhu, Jia; Gao, Weimin

    2018-05-10

    Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells. Four different NSCLC cell lines (A549, H460, H1650, and H1975) were used. Cytotoxicity, in vitro tumorigenicity, gene expression, and protein expression were analyzed by MTT assay, soft agar assay, real-time PCR, and Western blots, respectively. Among the 14 components in LJSJF, SB was the only one to possess cytotoxic effects at its pharmacologically relevant doses. Additionally, we observed synergistically dose-dependent cytotoxic effects of SB in combination with other LJSJF components. After SB or LJSJF treatment, significant reductions in colony number and/or size were observed in A549 and H460; a notable dose-dependent decrease in EGFR was observed in A549, H460, and H1650; significant downregulation in EGFR and its downstream signaling targets mTOR and p38MAPK were also observed in A549 and H460; and p53 and p21 were significantly increased while survivin, cyclin D1, and MDM2 were significantly decreased in A549. Additionally, p53, p21, and Mettl7b were decreased, but p73 was increased in H460. Neither EGFR nor p53 was changed in H1975. Therefore, SB or LJSJF may induce cytotoxic effects by regulating multiple and/or distinct apoptotic pathways in different NSCLC cells. LJSJF exerts more pronounced cytotoxic effects against NSCLC cells than SB does by synergistically regulating the underlining molecular mechanisms including EGFR and/or p53 signaling pathways. Copyright © 2018 Elsevier B.V. All

  9. uPAR as anti-cancer target

    DEFF Research Database (Denmark)

    Lund, Ida K; Illemann, Martin; Thurison, Tine

    2011-01-01

    , and a potential diagnostic and predictive impact of the different uPAR forms has been reported. Hence, pericellular proteolysis seems to be a suitable target for anti-cancer therapy and numerous approaches have been pursued. Targeting of this process may be achieved by preventing the binding of uPA to u...... using mouse monoclonal antibodies (mAbs) against mouse uPA or uPAR. These reagents will target uPA and uPAR in both stromal cells and cancer cells, and their therapeutic potential can now be assessed in syngenic mouse cancer models....

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

    CSIR Research Space (South Africa)

    Korir, E

    2014-01-01

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

  11. Enabling Anticancer Therapeutics by Nanoparticle Carriers: The Delivery of Paclitaxel

    Directory of Open Access Journals (Sweden)

    Bing Yan

    2011-07-01

    Full Text Available Anticancer drugs, such as paclitaxel (PTX, are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to enable drug delivery due to their low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. This review takes paclitaxel as an example and compares different nanoparticle-based delivery systems for their effectiveness in cancer chemotherapy.

  12. Rulings in Argentinean and Colombian courts decriminalize possession of small amounts of narcotics.

    Science.gov (United States)

    Cozac, David

    2009-12-01

    Two recent court decisions in South America have reflected a growing backlash in the region against the so-called, U.S.-led "war on drugs". In Argentina, the Supreme Court of Justice ruled unanimously on 25 August 2009 that the second paragraph of Article 14 of the country's drug control legislation, which punishes the possession of drugs for personal consumption, was unconstitutional. In Colombia, the Supreme Court of Justice ruled on 8 July 2009 that the possession of illegal drugs for personal use was not a criminal offence.

  13. Racial and Ethnic Differences in Advance Directive Possession: Role of Demographic Factors, Religious Affiliation, and Personal Health Values in a National Survey of Older Adults.

    Science.gov (United States)

    Huang, Ivy A; Neuhaus, John M; Chiong, Winston

    2016-02-01

    Black and Hispanic older Americans are less likely than white older Americans to possess advance directives. Understanding the reasons for this racial and ethnic difference is necessary to identify targets for future interventions to improve advance care planning in these populations. The aim of the study was to evaluate whether racial and ethnic differences in advance directive possession are explained by other demographic factors, religious characteristics, and personal health values. A general population survey was conducted in a nationally representative sample using a web-enabled survey panel of American adults aged 50 and older (n = 2154). In a sample of older Americans, white participants are significantly more likely to possess advance directives (44.0%) than black older Americans (24.0%, p personal health values. These findings support targeted efforts to mitigate racial disparities in access to advance care planning.

  14. Virtual Dual inhibition of COX-2 / 5-LOX enzymes based on binding properties of alpha-amyrins, the anti-inflammatory compound as a promising anti-cancer drug

    Science.gov (United States)

    Ranjbar, Mohammad Mehdi; Assadolahi, Vahideh; Yazdani, Mohsen; Nikaein, Donya; Rashidieh, Behnam

    2016-01-01

    Hydro-alcoholic fruit extract of Cordia myxa was considerably effective on curing acute inflammation in mouse model. Previous studies suggested significant anti-inflammatory activities as well as potential anticancer agent of α-amyrins in seeds. Inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipooxygenase (5-LOX) is significant in cancer prevention and therapeutics although this inhibition with chemo-drugs has its own side-effects. It is shown that these enzymes pathways are related to several cancers including colon, breast and lung cancer. This study was conducted based on Cordia species' α-amyrins as a safer natural anti-cancer compound for inhibition of COX-2 and 5-LOX enzymes by molecular docking. The X-ray crystal structure of COX2 / 5-LOX enzymes and α-amyrins was retrieved and energetically minimized respectively. The binding site and surface of enzymes were detected. Docking studies were performed by AutoDock 4.2 using Lamarckian genetic algorithm (LGA). Finally drug likeness, molecular pharmacokinetic properties and toxicity of α-amyrins was calculated. Molecular Docking revealed hydrogen and hydrophobic interactions between α-amyrins with both active sites of COX-2 and 5-LOX enzymes. Interestingly, it covalently bonded to Fe cofactor of 5-LOX enzyme and chelated this molecule. Base on binding energies (∆G) α-amyrin has more inhibitory effects on 5-LOX (-10.45 Kcal/mol) than COX-2 (-8.02 Kcal/mol). Analysis of molecular pharmacokinetic parameters suggested that α-amyrins complied with most sets of Lipinski's rules, and so it could be a suitable ligand for docking studies. Eventually, bioactivity score showed α-amyrins possess considerable biological activities as nuclear receptor, enzyme inhibitor, GPCR and protease inhibitor ligand. These results clearly demonstrate that α-amyrins could act as potential highly selective COX-/5-LOX inhibitor. Also, it is a safe compound in comparison with classical non-steroidal anti-inflammatory drugs (NSAIDs

  15. ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments.

    Science.gov (United States)

    Hatakeyama, Shinji; Summermatter, Serge; Jourdain, Marie; Melly, Stefan; Minetti, Giulia C; Lach-Trifilieff, Estelle

    2016-01-01

    Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced cancer often receive anti-cancer therapies against their specific cancer type as a standard of care, and whether specific ActRII inhibition is efficacious when combined with anti-cancer agents has not been elucidated yet. In this study, we evaluated interactions between ActRII blockade and anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model. CDD866 (murinized version of bimagrumab) is a neutralizing antibody against the activin receptor type II (ActRII) preventing binding of ligands such as myostatin and activin A, which are involved in cancer cachexia. CDD866 was evaluated in association with cisplatin as a standard cytotoxic agent or with everolimus, a molecular-targeted agent against mammalian target of rapamycin (mTOR). In the early studies, the treatment effect on cachexia was investigated, and in the additional studies, the treatment effect on progression of cancer and the associated cachexia was evaluated using body weight loss or tumor volume as interruption criteria. Cisplatin accelerated body weight loss and tended to exacerbate skeletal muscle loss in cachectic animals, likely due to some toxicity of this anti-cancer agent. Administration of CDD866 alone or in combination with cisplatin protected from skeletal muscle weight loss compared to animals receiving only cisplatin, corroborating that ActRII inhibition remains fully efficacious under cisplatin treatment. In contrast, everolimus treatment alone significantly protected the tumor-bearing mice against skeletal muscle weight loss caused by CT-26 tumor. CDD866 not only remains efficacious in the presence of everolimus but also showed a non-significant trend for an additive effect on reversing skeletal muscle weight loss. Importantly, both combination therapies slowed down time

  16. In vitro antioxidant and anticancer effects of solvent fractions from Prunella vulgaris var. lilacina.

    Science.gov (United States)

    Hwang, Yu-Jin; Lee, Eun-Ju; Kim, Haeng-Ran; Hwang, Kyung-A

    2013-11-09

    Recently, considerable attention has been focused on exploring the potential antioxidant properties of plant extracts or isolated products of plant origin. Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and it continues to be used to treat inflammation, eye pain, headache, and dizziness. However, reports on the antioxidant activities of P. vulgaris var. lilacina are limited, particularly concerning the relationship between its phenolic content and antioxidant capacity. In this study, we investigated the antioxidant and anticancer activities of an ethanol extract from P. vulgaris var. lilacina and its fractions. Dried powder of P. vulgaris var. lilacina was extracted with ethanol, and the extract was fractionated to produce the hexane fraction, butanol fraction, chloroform fraction and residual water fraction. The phenolic content was assayed using the Folin-Ciocalteu colorimetric method. Subsequently, the antioxidant activities of the ethanol extract and its fractions were analyzed employing various antioxidant assay methods including DPPH, FRAP, ABTS, SOD activity and production of reactive oxygen species. Additionally, the extract and fractions were assayed for their ability to exert cytotoxic activities on various cancer cells using the MTT assay. We also investigated the expression of genes associated with apoptotic cell death by RT-PCR. The total phenolic contents of the ethanol extract and water fraction of P. vulgaris var. lilacina were 303.66 and 322.80 mg GAE/g dry weight (or fractions), respectively. The results showed that the ethanol extract and the water fraction of P. vulgaris var. lilacina had higher antioxidant content than other solvent fractions, similar to their total phenolic content. Anticancer activity was also tested using the HepG2, HT29, A549, MKN45 and HeLa cancer cell lines. The results clearly demonstrated that the P. vulgaris var. lilacina ethanol extract induced significant cytotoxic effects

  17. Characterizing the Effective Bandwidth of Nonlinear Vibratory Energy Harvesters Possessing Multiple Stable Equilibria

    Science.gov (United States)

    Panyam Mohan Ram, Meghashyam

    In the last few years, advances in micro-fabrication technologies have lead to the development of low-power electronic devices spanning critical fields related to sensing, data transmission, and medical implants. Unfortunately, effective utilization of these devices is currently hindered by their reliance on batteries. In many of these applications, batteries may not be a viable choice as they have a fixed storage capacity and need to be constantly replaced or recharged. In light of such challenges, several novel concepts for micro-power generation have been recently introduced to harness, otherwise, wasted ambient energy from the environment and maintain these low-power devices. Vibratory energy harvesting is one such concept which has received significant attention in recent years. While linear vibratory energy harvesters have been well studied in the literature and their performance metrics have been established, recent research has focused on deliberate introduction of stiffness nonlinearities into the design of these devices. It has been shown that, nonlinear energy harvesters have a wider steady-state frequency bandwidth as compared to their linear counterparts, leading to the premise that they can used to improve performance, and decrease sensitivity to variations in the design and excitation parameters. This dissertation aims to investigate this premise by developing an analytical framework to study the influence of stiffness nonlinearities on the performance and effective bandwidth of nonlinear vibratory energy harvesters. To achieve this goal, the dissertation is divided into three parts. The first part investigates the performance of bi-stable energy harvesters possessing a symmetric quartic potential energy function under harmonic excitations and carries out a detailed analysis to define their effective frequency bandwidth. The second part investigates the relative performance of mono- and bi-stable energy harvesters under optimal electric loading

  18. Enhanced osteoblast adhesion on nanostructured selenium compacts for anti-cancer orthopedic applications

    Directory of Open Access Journals (Sweden)

    Phong Tran

    2008-10-01

    Full Text Available Phong Tran1, Thomas J Webster21Physics Department; 2Division of Engineering and Department of Orthopedics, Brown University, Providence, USAAbstract: Metallic bone implants possess numerous problems limiting their long-term efficacy, such as poor prolonged osseointegration, stress shielding, and corrosion under in vivo environments. Such problems are compounded for bone cancer patients since numerous patients receive orthopedic implants after cancerous bone resection. Unfortunately, current orthopedic materials were not originally developed to simultaneously increase healthy bone growth (as in traditional orthopedic implant applications while inhibiting cancerous bone growth. The long-term objective of the present research is to investigate the use of nano-rough selenium to prevent bone cancer from re-occurring while promoting healthy bone growth for this select group of cancer patients. Selenium is a well known anti-cancer chemical. However, what is not known is how healthy bone cells interact with selenium. To determine this, selenium, spherical or semispherical shots, were pressed into cylindrical compacts and these compacts were then etched using 1N NaOH to obtain various surface structures ranging from the micron, submicron to nano scales. Changes in surface chemistry were also analyzed. Through these etching techniques, results of this study showed that biologically inspired surface roughness values were created on selenium compacts to match that of natural bone roughness. Moreover, results showed that healthy bone cell adhesion increased with greater nanometer selenium roughness (more closely matching that of titanium. In this manner, this study suggests that nano-rough selenium should be further tested for orthopedic applications involving bone cancer treatment.Keywords: selenium, nano-rough, osteoblast, cancer, chemopreventive

  19. The putative roles of the ubiquitin/proteasome pathway in resistance to anticancer therapy.

    Science.gov (United States)

    Smith, Laura; Lind, Michael J; Drew, Philip J; Cawkwell, Lynn

    2007-11-01

    The ubiquitin/proteasome (UP) pathway plays a significant role in many important biological functions and alterations in this pathway have been shown to contribute to the pathology of many human diseases, including cancer. Proteasome inhibition has been well established as a rational strategy for the treatment of multiple myeloma and is currently under investigation for the treatment of other haematological malignancies and solid tumours. Recent evidence suggests that proteasome inhibition may also sensitise tumour cells to the actions of both conventional chemotherapy and radiotherapy, suggesting that this pathway may modify clinical response to anticancer therapy. However, conflicting evidence exists as to the roles of the UP pathway in resistance to treatment. This review endeavours to discuss such roles.

  20. Anti-cancer potential of banana flower extract: An in vitro study

    Directory of Open Access Journals (Sweden)

    Varalakshmi Kilingar Nadumane

    2014-12-01

    Full Text Available Banana (Musa paradisiaca flower is rich in phytochemicals (vitamins, flavonoids, proteins and has antioxidant properties. The anti-cancer activity of banana flower extract has been evaluated on the cervical cancer cell line HeLa. The antiproliferative effects were evaluated by MTT assay. The extract was further purified by TLC and characterized by LC-MS method. The ethanol extract had significant cytotoxicity to HeLa cells with an IC50 of 20 µg/mL. By thin layer chromatography we could isolate three fractions out of which fraction 2 had exhibited maximum anti-proliferative effects with an IC50 value of <10 µg/mL. By LC-MS analysis, bioactive fraction was found to have an m/z value of 224.2 indicating it as a novel one.

  1. Photolabile ruthenium complexes to cage and release a highly cytotoxic anticancer agent.

    Science.gov (United States)

    Wei, Jianhua; Renfrew, Anna K

    2018-02-01

    CHS-828 (N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N″-4-pyridyl guanidine) is an anticancer agent with low bioavailability and high systemic toxicity. Here we present an approach to improve the therapeutic profile of the drug using photolabile ruthenium complexes to generate light-activated prodrugs of CHS-828. Both prodrug complexes are stable in the dark but release CHS-828 when irradiated with visible light. The complexes are water-soluble and accumulate in tumour cells in very high concentrations, predominantly in the mitochondria. Both prodrug complexes are significantly less cyototoxic than free CHS-828 in the dark but their toxicity increases up to 10-fold in combination with visible light. The cellular responses to light treatment are consistent with release of the cytotoxic CHS-828 ligand. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    1984-11-01

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

  4. Plant Sterols as Anticancer Nutrients: Evidence for Their Role in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Bruce J. Grattan

    2013-01-01

    Full Text Available While many factors are involved in the etiology of cancer, it has been clearly established that diet significantly impacts one’s risk for this disease. More recently, specific food components have been identified which are uniquely beneficial in mitigating the risk of specific cancer subtypes. Plant sterols are well known for their effects on blood cholesterol levels, however research into their potential role in mitigating cancer risk remains in its infancy. As outlined in this review, the cholesterol modulating actions of plant sterols may overlap with their anti-cancer actions. Breast cancer is the most common malignancy affecting women and there remains a need for effective adjuvant therapies for this disease, for which plant sterols may play a distinctive role.

  5. Strategies to enhance the anticancer potential of TNF.

    Science.gov (United States)

    Pilati, Pierluigi; Rossi, Carlo Riccardo; Mocellin, Simone

    2008-01-01

    Although tumor necrosis factor (TNF) antitumor activity is evident in several preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Furthermore, due to systemic toxicity, TNF can only be administered via sophisticated drug-delivery systems in patients with solid tumors confined to one extremity or organ. The impossibility to administer TNF systemically does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. Dissecting the cascade of molecular events underlying tumor sensitivity to TNF researchers will allow to further exploit the anticancer potential of this molecule. The rational for the development of strategies aimed at sensitizing malignant cells to TNF is to modulate tumor-specific molecular derangements in order to maximize the selectivity of TNF cytotoxicity towards cancer. This would enhance the anticancer activity of current TNF-based locoregional regimens and would pave the way to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field.

  6. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2016-07-01

    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

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

    Science.gov (United States)

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

    2014-01-01

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

  8. Genetic Interactions of STAT3 and Anticancer Drug Development

    International Nuclear Information System (INIS)

    Fang, Bingliang

    2014-01-01

    Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors

  9. Anticancer Activity from Active Fraction of Sea Cucumber

    Directory of Open Access Journals (Sweden)

    Nurul Mutia Putram

    2017-05-01

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

  10. PRESCRIPTION PATTERN OF ANTICANCER DRUGS IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Mary Rohini

    2015-05-01

    Full Text Available Carcinoma is one of the most common cause of morbidity and mortality all over the world . Chemotherapy is main stay of treatment with other modalities in the management. Present study had been conducted to evaluate prescribing pattern of anticancer drugs. An observational, retrospective study was conducted in the oncology department of ESI hos pital over a period of one year. Data of patients greater than 19 years and diagnosed as carcinoma were included in the study. Out of 197 enrolled patients, majority were female (134, 68% and in the age group of 41 - 60 years (147, 74.61% patients. Carcino ma of breast (58, 29.44% was most commonly reported followed by carcinoma head and neck (46, 23.35%, and carcinoma cervix (34, 17.25%. Chemotherapy was commonly used as combination regimens (160, 81.21%. 5 - Fluoro Uracil (5 - FU and platinum based combin ation were most frequently prescribed (60, 30.45% especially in head and neck carcinoma (46, 23.35%. Platinum based combinations were also used in management of lung carcinoma. Dexamethasone, Ranitidine, Ondansetron, were used as palliative therapy eithe r to prevent or manage adverse reactions of anticancer drugs

  11. Telomerase Inhibitors from Natural Products and Their Anticancer Potential

    Directory of Open Access Journals (Sweden)

    Kumar Ganesan

    2017-12-01

    Full Text Available Telomeres and telomerase are nowadays exploring traits on targets for anticancer therapy. Telomerase is a unique reverse transcriptase enzyme, considered as a primary factor in almost all cancer cells, which is mainly responsible to regulate the telomere length. Hence, telomerase ensures the indefinite cell proliferation during malignancy—a hallmark of cancer—and this distinctive feature has provided telomerase as the preferred target for drug development in cancer therapy. Deactivation of telomerase and telomere destabilization by natural products provides an opening to succeed new targets for cancer therapy. This review aims to provide a fundamental knowledge for research on telomere, working regulation of telomerase and its various binding proteins to inhibit the telomere/telomerase complex. In addition, the review summarizes the inhibitors of the enzyme catalytic subunit and RNA component, natural products that target telomeres, and suppression of transcriptional and post-transcriptional levels. This extensive understanding of telomerase biology will provide indispensable information for enhancing the efficiency of rational anti-cancer drug design.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Urszula Gawlik-Dziki

    2014-01-01

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

  14. Effects of Offense, Defense, and Ball Possession on Mobility Performance in Wheelchair Basketball

    NARCIS (Netherlands)

    de Witte, Annemarie M. H.; Berger, Monique A. M.; Hoozemans, Marco J. M.; Veeger, Dirkjan H. E. J.; van der Woude, Lucas H. V.

    2017-01-01

    The aim of this study was to determine to what extent mobility performance is influenced by offensive or defensive situations and ball possession and to what extent these actions are different for the field positions. From video analysis, the relative duration of the various wheelchair movements

  15. What does it mean to be possessed by a spirit or demon? Some ...

    African Journals Online (AJOL)

    2015-07-08

    Jul 8, 2015 ... Commons Attribution. License. .... Klass (2003:3) I therefore want to ask the question: 'What is actually .... help to categorise possession in terms of possible causal ... control of life. .... a social structure, the complex formed by all his [her] social ... a way to cope with stressful experiences and, together with.

  16. Competences possessed and required by European graduates. REFLEX Report to HEFCE No 4

    OpenAIRE

    Little, Brenda; Braun, Edith; Tang, Win-Yee

    2008-01-01

    The report is based on the results of a major international study of graduate employment some five years after graduation. It presents an analysis of graduates' perceptions of what competences they need to do their current jobs and whether they possess these competences.

  17. 31 CFR 601.5 - Penalty for unauthorized control or possession.

    Science.gov (United States)

    2010-07-01

    ... CURRENCY AND OTHER SECURITIES § 601.5 Penalty for unauthorized control or possession. The Secretary of the... heretofore adopted for the printing of paper currency or other obligations or securities of the United States, is and will be subject to the provisions of 18 U.S.C. 474A which provides, in part, that it is...

  18. 7 CFR 330.300 - Soil from foreign countries or Territories or possessions. 1

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Soil from foreign countries or Territories or possessions. 1 330.300 Section 330.300 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FEDERAL PLANT PEST REGULATIONS; GENERAL; PLANT PESTS; SOIL, STONE, AND QUARRY...

  19. What does it mean to be possessed by a spirit or demon? Some ...

    African Journals Online (AJOL)

    The visible growth in possession and exorcism in Southern Africa can, amongst others, be attributed to the general impression in Christianity that, since Jesus was a successful exorcist, his followers should follow his example. Historical Jesus research generally endorses a view of Jesus as exorcist, which probably also ...

  20. 50 CFR 648.322 - Skate allocation, possession, and landing provisions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Skate allocation, possession, and landing provisions. 648.322 Section 648.322 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Management Measures for the NE Skate...

  1. 27 CFR 479.105 - Transfer and possession of machine guns.

    Science.gov (United States)

    2010-04-01

    ... a department, agency, or political subdivision thereof; or any lawful transfer or lawful possession... distribution to any department or agency of the United States or any State or political subdivision thereof, or... entities expressing a need for a particular model or interest in seeing a demonstration of a particular...

  2. Logarithmic residues of analytic Banach algebra valued functions possessing a simply meromorphic inverse

    NARCIS (Netherlands)

    H. Bart (Harm); T. Ehrhardt; B. Silbermann

    2001-01-01

    textabstractA logarithmic residue is a contour integral of a logarithmic derivative (left or right) of an analytic Banach algebra valued function. For functions possessing a meromorphic inverse with simple poles only, the logarithmic residues are identified as the sums of idempotents. With the help

  3. Possession, Transportation, and Use of Firearms by Older Youth in 4-H Shooting Sports Programs

    Science.gov (United States)

    White, David J.; Williver, S. Todd

    2014-01-01

    Thirty years ago we would think nothing of driving to school with a jackknife in our pocket or rifle in the gun rack. Since then, the practices of possessing, transporting, and using firearms have been limited by laws, rules, and public perception. Despite restrictions on youth, the Youth Handgun Safety Act does afford 4-H shooting sports members…

  4. THE RELATIONSHIP BETWEEN RESEARCH AND TEACHING: THE CHART OF POSSESSIVE PRONOUNS IN PORTUGUESE

    Directory of Open Access Journals (Sweden)

    Leonardo Lennertz Marcotulio

    2016-01-01

    Full Text Available The aim of this article is to investigate the relationship between research and teaching, concerning the rearrangements operated in the chart of possessive pronouns,  observing in which way sociolinguistic studies have been applied to the teaching of Portuguese through the didactic material prepared for High School and the courses of Portuguese as a Foreign Language.

  5. Effects of offense, defense, and ball possession on mobility performance in wheelchair basketball

    NARCIS (Netherlands)

    De Witte, Annemarie M.H.; Berger, Monique A.M.; Hoozemans, Marco J.M.; Veeger, H.E.J.; van der Woude, Lucas H.V.

    2017-01-01

    The aim of this study was to determine to what extent mobility performance is influenced by offensive or defensive situations and ball possession and to what extent these actions are different for the field positions. From video analysis, the relative duration of the various wheelchair movements

  6. How Risky Is Marijuana Possession? Considering the Role of Age, Race, and Gender

    Science.gov (United States)

    Nguyen, Holly; Reuter, Peter

    2012-01-01

    Arrest rates per capita for possession of marijuana have increased threefold over the last 20 years and now constitute the largest single arrest offense category. Despite the increase in arrest numbers, rates of use have remained stable during much of the same period. This article presents the first estimates of the arrest probabilities for…

  7. 27 CFR 478.40 - Manufacture, transfer, and possession of semiautomatic assault weapons.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Manufacture, transfer, and... COMMERCE IN FIREARMS AND AMMUNITION Administrative and Miscellaneous Provisions § 478.40 Manufacture, transfer, and possession of semiautomatic assault weapons. (a) Prohibition. No person shall manufacture...

  8. Whose name is it anyway? Varying patterns of possessive usage in eponymous neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Michael R. MacAskill

    2013-04-01

    Full Text Available There has been long-standing debate over whether use of the possessive form of the names of eponymous neurological disorders should be abandoned. Which view has actually predominated in practice? We empirically assessed current and historical usage in the scientific literature. The PubMed database was queried for the percentage of titles published each year from 1960–2012 which contained the possessive form of Parkinson’s (PD, Alzheimer’s (AD, Huntington’s (HD, Wilson’s (WD, and Gaucher’s (GD diseases (e.g. Huntington’s disease or chorea vs Huntington disease or chorea. Down syndrome (DS, well known for its changes in terminology, was used as a reference. The possessive form was nearly universal in all conditions from 1960 until the early 1970s. In both DS and GD it then declined at an approximately constant rate of 2 percentage points per year to drop below 15%. The possessive forms of both PD and AD began to decline at the same time but stabilised and have since remained above 80%, with a similar but more volatile pattern in HD. WD, meanwhile, is intermediate between the DS/GD and PD/AD/HD patterns, with a slower decline to its current value of approximately 60%. Declining possessive form usage in GD and DS papers has been remarkably uniform over time and has nearly reached completion. PD and AD appear stable in remaining predominantly possessive. The larger volume of papers published in those fields and their possibly greater public recognition and involvement may make that unlikely to change in the short-term. In a secondary analysis restricted to PD, we found that practices have switched dramatically several times in each of three US-published general neurology journals. Meanwhile, in two UK-published journals, and in the specialist title “Movement Disorders”, the possessive form has been maintained consistently. The use of eponyms in neurology shows systematic variation across time, disorders, and journals.

  9. Bio-fabrication of silver nanoparticles using the leaf extract of an ancient herbal medicine, dandelion (Taraxacum officinale), evaluation of their antioxidant, anticancer potential, and antimicrobial activity against phytopathogens.

    Science.gov (United States)

    Saratale, Rijuta G; Benelli, Giovanni; Kumar, Gopalakrishnan; Kim, Dong Su; Saratale, Ganesh D

    2018-04-01

    In recent years, the use of nanoparticle-based antimicrobials has been increased due to many advantages over conventional agrochemicals. This study investigates the utilization of common medicinal plant dandelion, Taraxacum officinale, for the synthesis of silver nanoparticles (TOL-AgNPs). AgNPs were evaluated for antimicrobial activity against two important phytopathogens, Xanthomonas axonopodis and Pseudomonas syringae. The morphology, size, and structure of TOL-AgNPs were characterized using UV-visible spectroscopy and X-ray diffraction (XRD). Fourier transform infrared spectroscopy (FT-IR) showed the presence of phytochemicals involved during synthesis of NPs. High-resolution transmission electron microscopy (HR-TEM) analysis shed light on the size of monodispersed spherical AgNPs ranging between 5 and 30 nm, with an average particle size of about 15 nm. The TOL-AgNPs (at 20 μg/mL concentration) showed significant antibacterial activity with significant growth inhibition of phytopathogens X. axonopodis (22.0 ± 0.84 mm) and P. syringae (19.5 ± 0.66 mm). The synthesized AgNPs had higher antibacterial activity in comparison with commercial AgNPs. Synergistic assays with standard antibiotics revealed that nanoformulations with tetracycline showed better broad-spectrum efficiency to control phytopathogens. They also possessed significant antioxidant potential in terms of ABTS (IC 50  = 45.6 μg/mL), DPPH (IC 50  = 56.1 μg/mL), and NO (IC 50  = 55.2 μg/mL) free radical scavenging activity. The TOL-AgNPs showed high cytotoxic effect against human liver cancer cells (HepG2). Overall, dandelion-mediated AgNPs synthesis can represent a novel approach to develop effective antimicrobial and anticancer drugs with a cheap and eco-friendly nature.

  10. Endogenously generated DNA nucleobase modifications source, and significance as possible biomarkers of malignant transformation risk, and role in anticancer therapy.

    Science.gov (United States)

    Olinski, Ryszard; Gackowski, Daniel; Cooke, Marcus S

    2018-01-01

    The DNA of all living cells undergoes continuous structural and chemical alteration, which may be derived from exogenous sources, or endogenous, metabolic pathways, such as cellular respiration, replication and DNA demethylation. It has been estimated that approximately 70,000 DNA lesions may be generated per day in a single cell, and this has been linked to a wide variety of diseases, including cancer. However, it is puzzling why potentially mutagenic DNA modifications, occurring at a similar level in different organs/tissue, may lead to organ/tissue specific cancers, or indeed non-malignant disease - what is the basis for this differential response? We suggest that it is perhaps the precise location of damage, within the genome, that is a key factor. Finally, we draw attention to the requirement for reliable methods for identification and quantification of DNA adducts/modifications, and stress the need for these assays to be fully validated. Once these prerequisites are satisfied, measurement of DNA modifications may be helpful as a clinical parameter for treatment monitoring, risk group identification and development of prevention strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

    Directory of Open Access Journals (Sweden)

    Brody LP

    2017-09-01

    Full Text Available Leigh P Brody,1,* Meliz Sahuri-Arisoylu,1,* James R Parkinson,1 Harry G Parkes,2 Po Wah So,3 Nabil Hajji,4 E Louise Thomas,1 Gary S Frost,5 Andrew D Miller,6,* Jimmy D Bell1,* 1Department of Life Sciences, Faculty of Science and Technology, University of Westminster, 2CR-UK Clinical MR Research Group, Institute of Cancer Research, Sutton, Surrey, 3Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 4Department of Medicine, Division of Experimental Medicine, Centre for Pharmacology & Therapeutics, Toxicology Unit, Imperial College London, 5Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6Institute of Pharmaceutical Science, King’s College London, London, UK *These authors contributed equally to this work Abstract: Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN. We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo. Keywords: lipid-based nanoparticles, liposomes, cancer, short-chain fatty acids, epigenetics

  12. 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.

  13. Lappaol F, a novel anticancer agent isolated from plant arctium Lappa L.

    Science.gov (United States)

    Sun, Qing; Liu, Kanglun; Shen, Xiaoling; Jin, Weixin; Jiang, Lingyan; Sheikh, M Saeed; Hu, Yingjie; Huang, Ying

    2014-01-01

    In an effort to search for new cancer-fighting therapeutics, we identified a novel anticancer constituent, Lappaol F, from plant Arctium Lappa L. Lappaol F suppressed cancer cell growth in a time- and dose-dependent manner in human cancer cell lines of various tissue types. We found that Lappaol F induced G(1) and G(2) cell-cycle arrest, which was associated with strong induction of p21 and p27 and reduction of cyclin B1 and cyclin-dependent kinase 1 (CDK1). Depletion of p21 via genetic knockout or short hairpin RNA (shRNA) approaches significantly abrogated Lappaol F-mediated G(2) arrest and CDK1 and cyclin B1 suppression. These results suggest that p21 seems to play a crucial role in Lappaol F-mediated regulation of CDK1 and cyclin B1 and G(2) arrest. Lappaol F-mediated p21 induction was found to occur at the mRNA level and involved p21 promoter activation. Lappaol F was also found to induce cell death in several cancer cell lines and to activate caspases. In contrast with its strong growth inhibitory effects on tumor cells, Lappaol F had minimal cytotoxic effects on nontumorigenic epithelial cells tested. Importantly, our data also demonstrate that Lappaol F exhibited strong growth inhibition of xenograft tumors in nude mice. Lappaol F was well tolerated in treated animals without significant toxicity. Taken together, our results, for the first time, demonstrate that Lappaol F exhibits antitumor activity in vitro and in vivo and has strong potential to be developed as an anticancer therapeutic.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2018-06-01

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

  16. Gun possession among American youth: a discovery-based approach to understand gun violence.

    Directory of Open Access Journals (Sweden)

    Kelly V Ruggles

    Full Text Available OBJECTIVE: To apply discovery-based computational methods to nationally representative data from the Centers for Disease Control and Preventions' Youth Risk Behavior Surveillance System to better understand and visualize the behavioral factors associated with gun possession among adolescent youth. RESULTS: Our study uncovered the multidimensional nature of gun possession across nearly five million unique data points over a ten year period (2001-2011. Specifically, we automated odds ratio calculations for 55 risk behaviors to assemble a comprehensive table of associations for every behavior combination. Downstream analyses included the hierarchical clustering of risk behaviors based on their association "fingerprint" to 1 visualize and assess which behaviors frequently co-occur and 2 evaluate which risk behaviors are consistently found to be associated with gun possession. From these analyses, we identified more than 40 behavioral factors, including heroin use, using snuff on school property, having been injured in a fight, and having been a victim of sexual violence, that have and continue to be strongly associated with gun possession. Additionally, we identified six behavioral clusters based on association similarities: 1 physical activity and nutrition; 2 disordered eating, suicide and sexual violence; 3 weapon carrying and physical safety; 4 alcohol, marijuana and cigarette use; 5 drug use on school property and 6 overall drug use. CONCLUSIONS: Use of computational methodologies identified multiple risk behaviors, beyond more commonly discussed indicators of poor mental health, that are associated with gun possession among youth. Implications for prevention efforts and future interdisciplinary work applying computational methods to behavioral science data are described.

  17. Enhanced Production of Gypenoside LXXV Using a Novel Ginsenoside-Transforming β-Glucosidase from Ginseng-Cultivating Soil Bacteria and Its Anti-Cancer Property

    Directory of Open Access Journals (Sweden)

    Chang-Hao Cui

    2017-05-01

    Full Text Available Minor ginsenosides, such as compound K, Rg3(S, which can be produced by deglycosylation of ginsenosides Rb1, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb1, is still unknown due to the rarity of its content in plants. Here, we cloned and characterized a novel ginsenoside-transforming β-glucosidase (BglG167b derived from Microbacterium sp. Gsoil 167 which can efficiently hydrolyze gypenoside XVII into gypenoside LXXV, and applied it to the production of gypenoside LXXV at the gram-scale with high specificity. In addition, the anti-cancer activity of gypenoside LXXV was investigated against three cancer cell lines (HeLa, B16, and MDA-MB231 in vitro. Gypenoside LXXV significantly reduced cell viability, displaying an enhanced anti-cancer effect compared to gypenoside XVII and Rb1. Taken together, this enzymatic method would be useful in the preparation of gypenoside LXXV for the functional food and pharmaceutical industries.

  18. Anticancer and antibacterial secondary metabolites from the endophytic fungus Penicillium sp. CAM64 against multi-drug resistant Gram-negative bacteria.

    Science.gov (United States)

    Jouda, Jean-Bosco; Tamokou, Jean-de-Dieu; Mbazoa, Céline Djama; Sarkar, Prodipta; Bag, Prasanta Kumar; Wandji, Jean

    2016-09-01

    The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., an endophytic fungus associated with leaves of Garcinia nobilis. The culture filtrate from the fermentation of Penicillium sp. was extracted and analyzed by liquid chromatography-mass spectrometry, and the major metabolites were isolated and identified by spectroscopic analyses and by comparison with published data. The antibacterial activity of the compounds was assessed by broth microdilution method while the anticancer activity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The fractionation of the crude extract afforded penialidin A-C (1-3), citromycetin (4), p-hydroxyphenylglyoxalaldoxime (5) and brefelfin A (6). All of the compounds tested here showed antibacterial activity (MIC = 0.50 - 128 µg/mL) against Gramnegative multi-drug resistance bacteria, Vibrio cholerae (causative agent of dreadful disease cholera) and Shigella flexneri (causative agent of shigellosis), as well as the significant anticancer activity (LC 50 = 0.88 - 9.21 µg/mL) against HeLa cells. The results obtained indicate that compounds 1-6 showed good antibacterial and anticancer activities with no toxicity to human red blood cells and normal Vero cells.

  19. Hydroxycamptothecin-loaded nanoparticles enhance target drug delivery and anticancer effect

    Directory of Open Access Journals (Sweden)

    Li Su

    2008-05-01

    Full Text Available Abstract Background Hydroxycamptothecin (HCPT has been shown to have activity against a broad spectrum of cancers. In order to enhance its tissue-specific delivery and anticancer activity, we prepared HCPT-loaded nanoparticles made from poly(ethylene glycol-poly(γ-benzyl-L-glutamate (PEG-PBLG, and then studied their release characteristics, pharmacokinetic characteristics, and anticancer effects. PEG-PBLG nanoparticles incorporating HCPT were prepared by a dialysis method. Scanning electron microscopy (SEM was used to observe the shape and diameter of the nanoparticles. The HCPT release characteristics in vitro were evaluated by ultraviolet spectrophotometry. A high-performance liquid chromatography (HPLC detection method for determining HCPT in rabbit plasma was established. The pharmacokinetic parameters of HCPT/PEG-PBLG nanoparticles were compared with those of HCPT. Results The HCPT-loaded nanoparticles had a core-shell spherical structure, with a core diameter of 200 nm and a shell thickness of 30 nm. Drug-loading capacity and drug encapsulation were 7.5 and 56.8%, respectively. The HCPT release profile was biphasic, with an initial abrupt release, followed by sustained release. The terminal elimination half-lives (t 1/2 β of HCPT and HCPT-loaded nanoparticles were 4.5 and 10.1 h, respectively. Peak concentrations (Cmax of HCPT and HCPT-loaded nanoparticles were 2627.8 and 1513.5 μg/L, respectively. The apparent volumes of distribution of the HCPT and HCPT-loaded nanoparticles were 7.3 and 20.0 L, respectively. Compared with a blank control group, Lovo cell xenografts or Tca8113 cell xenografts in HCPT or HCPT-loaded nanoparticle treated groups grew more slowly and the tumor doubling times were increased. The tumor inhibition effect in the HCPT-loaded nanosphere-treated group was significantly higher than that of the HCPT-treated group (p 0.05. Conclusion Compared to the HCPT- and control-treated groups, the HCPT-loaded nanoparticle

  20. Anti-Cancer Effect of Angelica Sinensis on Women’s Reproductive Cancer

    Directory of Open Access Journals (Sweden)

    Hong-Hong Zhu

    2012-06-01

    Full Text Available Objective: Danggui, the root of Angelica Sinensis, has traditionally been used for the treatment of women’s reproductive disorders in China for thousands of years. This study was to determine whether Danggui have potential anti-cancer effect on women’s cancer and its potential mechanism. Methods: Danggui was extracted by ethanol. The Cell Titer 96® Aqueous Non-Radioactive Cell Proliferation Assay was used to compare the effects of Danggui on human breast (MCF-7 and 7368 and cervical (CaSki and SiHa cancer cells with its effects on normal fibroblasts (HTB-125. A revised Ames test was used to test for antimutagenicity. The standard strains of Salmonella typhimarium (TA 100 and 102 were used in the test. Methyl methane sulfonate (MMS and UV light were used as positive mutagen controls and ethanol and double distilled water (DDW as controls. The SAS statistical software was used to analyze the data. Results: Danggui was found to be much more toxic to all cancer cell lines tested than to normal fibroblasts. There was a significant negative dose-effect relationship between Danggui and cancer cell viability. Average viability of MCF-7 was 69.5%, 18.4%, 5.7%, 5.7%, and 5.0% of control for Danggui doses 0.07, 0.14, 0.21, 0.32, and 0.64 ug/ul, respectively, with a Ptrend < 0.0001. Half maximal inhibitory dose (ID50 of Danggui for cancer cell lines MCF-7, CaSki, SiHa and CRL-7368 was 0.10, 0.09, 0.10 and 0.07 ug/ul, Functional Foods in Health and Disease 2012, 2(6:242-250respectively. For the normal fibroblasts, ID50 was 0.58 ug/ul. At a dose of 0.32 ug/ul, Danggui killed over 90% of the cells in each cancer cell line, but at the same dose, only 12.3 % of the normal HTB-125 cells were killed. Revertants per plate of TA 100 decreased with the introduction of increasing doses of Danggui extracts with a Ptrend < 0.0001 when UV light was used as a mutagen. There was no difference in revertants per plate between ethanol and DDW control groups. Conclusions

  1. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    van Leeuwen, R. W. F.; Brundel, D. H. S.; Neef, C.; van Gelder, T.; Mathijssen, R. H. J.; Burger, D. M.; Jansman, F. G. A.

    2013-01-01

    Background: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. Methods: A

  2. Pharmacokinetic-Pharmacodynamic Modelling & Simulation for Anticancer Drugs with Complex Absorption Characteristics

    NARCIS (Netherlands)

    Yu, Huixin

    2016-01-01

    Cancer is still one of the leading causes of death in the world. In recent years, targeted anticancer agents have shown to be a major breakthrough in the battle against cancer. These targeted anticancer agents, mostly administered orally, specifically target molecular defects of tumour cells

  3. Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs

    NARCIS (Netherlands)

    R.W.F. van Leeuwen (Roelof); D.H.S. Brundel (D. H S); C. Neef (Cees); T. van Gelder (Teun); A.H.J. Mathijssen (Ron); D.M. Burger (David); F.G.A. Jansman (Frank)

    2013-01-01

    textabstractBackground: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.

  4. The effect of playing tactics and situational variables on achieving score-box possessions in a professional soccer team.

    Science.gov (United States)

    Lago-Ballesteros, Joaquin; Lago-Peñas, Carlos; Rey, Ezequiel

    2012-01-01

    The aim of this study was to analyse the influence of playing tactics, opponent interaction and situational variables on achieving score-box possessions in professional soccer. The sample was constituted by 908 possessions obtained by a team from the Spanish soccer league in 12 matches played during the 2009-2010 season. Multidimensional qualitative data obtained from 12 ordered categorical variables were used. Sampled matches were registered by the AMISCO PRO system. Data were analysed using chi-square analysis and multiple logistic regression analysis. Of 908 possessions, 303 (33.4%) produced score-box possessions, 477 (52.5%) achieved progression and 128 (14.1%) failed to reach any sort of progression. Multiple logistic regression showed that, for the main variable "team possession type", direct attacks and counterattacks were three times more effective than elaborate attacks for producing a score-box possession (P tactics on producing score-box possessions.

  5. Detecting Novelty and Significance

    Science.gov (United States)

    Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

    2013-01-01

    Studies of cognition often use an “oddball” paradigm to study effects of stimulus novelty and significance on information processing. However, an oddball tends to be perceptually more novel than the standard, repeated stimulus as well as more relevant to the ongoing task, making it difficult to disentangle effects due to perceptual novelty and stimulus significance. In the current study, effects of perceptual novelty and significance on ERPs were assessed in a passive viewing context by presenting repeated and novel pictures (natural scenes) that either signaled significant information regarding the current context or not. A fronto-central N2 component was primarily affected by perceptual novelty, whereas a centro-parietal P3 component was modulated by both stimulus significance and novelty. The data support an interpretation that the N2 reflects perceptual fluency and is attenuated when a current stimulus matches an active memory representation and that the amplitude of the P3 reflects stimulus meaning and significance. PMID:19400680

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  7. Significant NRC Enforcement Actions

    Data.gov (United States)

    Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

  8. Boron nitride nanotubes for delivery of 5-fluorouracil as anticancer drug: a theoretical study

    Science.gov (United States)

    Shayan, Kolsoom; Nowroozi, Alireza

    2018-01-01

    The electronic structure and properties of the armchair boron nitride nanotubes (BNNTs) interacted with the 5-FU drug, as an anticancer drug, are studied at the B3LYP/6-31G(d,p) level of theory. D3-Corrections were carried out for the treatment of intermolecular interactions in the hybrid complexes and encapsulated nanotubes, exactly. Results have shown that the encapsulation and adsorption of 5-FU molecule on the studied BNNTs surface are favorable processes, with a few exceptions. Also, it is found that the encapsulated nanotubes are stable than the hybrid complexes. Furthermore, we estimated the strengths of the intermolecular bonds of the benchmark systems by energetic, geometric, topological and molecular orbital descriptors. Some analyses have been made to explore any changes in the binding characteristics of the drug molecule after its attachment to the nanotubes. According to the NBO results, the charge transfer phenomenon is observed from the bonding or nonbonding orbitals of drug to the antibonding orbitals of BNNTs. Moreover, HOMO-LUMO analysis indicated that, after the adsorption process, the HOMO value slightly increased, while the LUMO value in these systems significantly reduced in the both of Drug@BNNTs groups. So, the energy gaps between HOMO and LUMO (Eg) are reduced, which emphasis on the greater intermolecular bond strength. Finally, the stability and reactivity of the Drug@BNNTs complexes have been examined from the magnitudes of the chemical reactivity descriptors such as chemical potential, global hardness, and electrophilicity index. As a consequence, BNNTs can be considered as a drug delivery vehicle for the transportation of 5-FU as anticancer drug within the biological systems.

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

    KAUST Repository

    Hasan, Mohammed Nihal

    2018-02-09

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

  10. [Evolution of reimbursement of high-cost anticancer drugs: Financial impact within a university hospital].

    Science.gov (United States)

    Baudouin, Amandine; Fargier, Emilie; Cerruti, Ariane; Dubromel, Amélie; Vantard, Nicolas; Ranchon, Florence; Schwiertz, Vérane; Salles, Gilles; Souquet, Pierre-Jean; Thomas, Luc; Bérard, Frédéric; Nancey, Stéphane; Freyer, Gilles; Trillet-Lenoir, Véronique; Rioufol, Catherine

    2017-06-01

    In the context of health expenses control, reimbursement of high-cost medicines with a 'minor' or 'nonexistent' improvement in actual health benefit evaluated by the Haute Autorité de santé is revised by the decree of March 24, 2016 related to the procedure and terms of registration of high-cost pharmaceutical drugs. This study aims to set up the economic impact of this measure. A six months retrospective study was conducted within a French university hospital from July 1, 2015 to December 31, 2015. For each injectable high-cost anticancer drug prescribed to a patient with cancer, the therapeutic indication, its status in relation to the marketing authorization and the associated improvement in actual health benefit were examined. The total costs of these treatments, the cost per type of indication and, in the case of marketing authorization indications, the cost per improvement in actual health benefit were evaluated considering that all drugs affected by the decree would be struck off. Over six months, 4416 high-cost injectable anticancer drugs were prescribed for a total cost of 4.2 million euros. The costs of drugs with a minor or nonexistent improvement in actual benefit and which comparator is not onerous amount 557,564 euros. The reform of modalities of inscription on the list of onerous drugs represents a significant additional cost for health institutions (1.1 million euros for our hospital) and raises the question of the accessibility to these treatments for cancer patients. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  11. Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong, E-mail: pharmsong@henu.edu.cn [Henan University, Institute of Pharmacy (China)

    2016-11-15

    Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

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

    KAUST Repository

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

    2018-01-01

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

  13. Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

    International Nuclear Information System (INIS)

    Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong

    2016-01-01

    Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

  14. [A nosology for supernatural phenomena and the construction of the 'possessed' brain in the nineteenth century].

    Science.gov (United States)

    Goncalves, Valeria Portugal; Ortega, Francisco

    2013-06-01

    At the end of the twentieth century, supernatural phenomena such as so called trances and possession by spirits received a scientific classification, which includes the numerous diagnoses of the dominant psychiatry. At the end of the nineteenth century we can observe a process of scientific categorization of phenomena considered to have originated in superstition or popular imagination. In this work we show how trances and spiritual possession were studied by Franz Anton Mesmer and his followers when developing the concept of magnetism; by James Braid during the creation of his theory of hypnosis; and by Jean Martin Charcot, which marked the entry of hysteria into nosological classification. Despite the differences between these schools, we identify the use of the brain and cerebral metaphors as the foundation of theories of the mind.

  15. Physicochemical properties of polysaccharides from Lentinus edodes under high pressure cooking treatment and its enhanced anticancer effects.

    Science.gov (United States)

    Li, Weiwei; Wang, Jingya; Chen, Zhongqin; Gao, Xudong; Chen, Yue; Xue, Zihan; Guo, Qingwen; Ma, Qiqi; Chen, Haixia

    2018-04-22

    This study was to investigate the physicochemical properties and anticancer effects of polysaccharides from Lentinus edodes extracted under high pressure cooking treatment (HPLPS) in vitro and in vivo. The extraction efficiency was improved. The main molecular weight of HPLPS was about 540 and about 227 kDa. And the inhibitory effects on HepG2 and HeLa cells of HPLPS were significantly increased (p Lentinus edodes might be effectively used for the treatment of hepatocellular carcinoma through its antioxidant and immunomodulatory effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

    Science.gov (United States)

    Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

    2012-02-01

    The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings.

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

    Science.gov (United States)

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

    2010-07-01

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

  18. Silibinin inhibits translation initiation: implications for anticancer therapy.

    Science.gov (United States)

    Lin, Chen-Ju; Sukarieh, Rami; Pelletier, Jerry

    2009-06-01

    Silibinin is a nontoxic flavonoid reported to have anticancer properties. In this study, we show that silibinin exhibits antiproliferative activity on MCF-7 breast cancer cells. Exposure to silibinin leads to a concentration-dependent decrease in global protein synthesis associated with reduced levels of eukaryotic initiation factor 4F complex. Moreover, polysome profile analysis of silibinin-treated cells shows a decrease in polysome content and translation of cyclin D1 mRNA. Silibinin exerts its effects on translation initiation by inhibiting the mammalian target of rapamycin signaling pathway by acting upstream of TSC2. Our results show that silibinin blocks mammalian target of rapamycin signaling with a concomitant reduction in translation initiation, thus providing a possible molecular mechanism of how silibinin can inhibit growth of transformed cells.

  19. Plant Phenolics: Extraction, Analysis and Their Antioxidant and Anticancer Properties

    Directory of Open Access Journals (Sweden)

    Jin Dai

    2010-10-01

    Full Text Available Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro and in-vivo animal models are viewed, including recent human intervention studies. Finally, possible mechanisms of action involving antioxidant and pro-oxidant activity as well as interference with cellular functions are discussed.

  20. Anticancer Properties of Psidium guajava - a Mini-Review.

    Science.gov (United States)

    Correa, Mariana Goncalves; Couto, Jessica Soldani; Teodoro, Anderson Junger

    2016-01-01

    Cancer is a complex disease caused by a progressive accumulation of multiple genetic mutations. Consumption of fruits is associated with lower risk of several cancers, which is mainly associated to their phytochemical content. The use of functional foods and chemopreventive compounds seems to contribute in this process, acting by mechanisms of antioxidant, anti-inflammatory, anti-angiogenic and hormonal. The Psidium Guajava has high potential functional related to pigments who are involved in the process of cancer prevention by having antioxidant activity. The aim of the present review is to expose some chemical compounds from P. Guajava fractions and their association with anti-carcinogenic function. The evidences supports the theory of anticancer properties of P. Guajava, although the mechanisms are still not fully elucidated, but may include scavenging free radicals, regulation of gene expression, modulation of cellular signalling pathways including those involved in DNA damage repair, cell proliferation and apoptosis.