Growth inhibition of human tumor cell lines by withanolides from Withania somnifera leaves.
ABSTRACT Ayurvedic medicines prepared in India consist of Withania somnifera roots as one of the main ingredients. It is consumed as a dietary supplement around the world. The leaves of W. somnifera were used in the treatment of tumors and inflammation in several Asian countries. We have isolated twelve withanolides such as withaferin A (1), sitoindoside IX (2), 4-(1-hydroxy-2, 2-dimethylcyclpropanone)-2, 3-dihydrowithaferin A (3), 2, 3-dihydrowithaferin A (4), 24, 25-dihydro-27-desoxywithaferin A (5), physagulin D (1-->6)-beta-D-glucopyranosyl- (1-->4)-beta-D-glucopyranoside (6), 27-O-beta-D-glucopyranosylphysagulin D (7), physagulin D (8), withanoside IV (9), and 27-O-beta-D-glucopyranosylviscosalactone B (10), 4, 16-dihydroxy-5beta, 6beta-epoxyphysagulin D (11), viscosalactone B (12) from the leaves of this species. Compounds 1-12 and diacetylwithaferin A (13) were tested for their antiproliferative activity on NCI-H460 (Lung), HCT-116 (Colon), SF-268 (Central Nervous System; CNS and MCF-7 (Breast) human tumor cell lines. The inhibitory concentration to afford 50% cell viability (IC50) for these compounds was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Withaferin A and its derivatives exhibited inhibitory concentrations (50%) ranging from 0.24 +/- 0.01 to 11.6 +/- 1.9 microg/mL. Viscosalactone B (12) showed the 50% inhibition at concentrations ranging from 0.32 +/- 0.05 to 0.47 +/- 0.15 microg/mL whereas its 27-O-glucoside derivative (10) exhibited IC50 between 7.9 +/- 2.9 and 17.3 +/- 3.9 microg/ml. However, Physagulin D type withanolides showed either weak or no activity at 30 microg/mL. Therefore, incorporation of withanolides in the diet may prevent or decrease the growth of tumors in human.
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ABSTRACT: Arsenic is present in the environment and human all over the world are exposed to small amounts, mostly through food, water, and air. In the developing countries like Bangladesh and India, the high prevalence of contamination, the isolation and poverty of the rural population and the high cost and complexity of arsenic removal systems have imposed a programmatic and policy challenge on an unprecedented scale. Although in India, Arsenic poisoning in ground water in Gangetic basin especially the districts adjoining the river Ganges right from Eastern Uttar Pradesh, Bihar to West Bengal is the major problem of concern. Due to which, major health related problems are arising in the population.To combat the present problem, a pre-clinical study was done on Charles foster rats and sodium arsenite at the dose of 8 mg Kg-1 body weight per day was administered to these rats for 60 days and upon these arsenic pretreated rats, novel plant extracts of Withania somnifera and Pteris longifolia were administered for 45 days to study the antidote effects of these plant extracts. These plants not only eliminated the toxic effects of arsenic but also reversed the normal physiological activity in the animal. Thus, the present study concludes that these novel plants possesses the best bioremedial impact against arsenic induced toxicity.
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ABSTRACT: Dibenzo[a,l]pyrene (DBP) has been found to be the most potent carcinogen of the polycyclic aromatic hydrocarbons (PAHs). Primary sources for DBP in the environment are combustion of wood and coal burning, gasoline and diesel exhaust, and tires. Given the likelihood of environmental exposure to DBP and strong experimental evidence of its potency, it is likely to contribute to lung cancer development. Intervention with compounds of natural origin ("phytochemicals") is considered an effective means to prevent cancer development and favorably modulate the underlying mechanisms, including DNA adduct formation. In this study, several agents have been identified that inhibit environmental carcinogen-induced DNA adduct formation using a cell-free microsomal system. Of the ten agents tested, resveratrol (648±26 adducts/10(9) nucleotides), oltipraz (1007±348 adducts/10(9) nucleotides), delphinidin (1252±142 adducts/10(9) nucleotides), tanshinone I (1981±213 adducts/10(9) nucleotides), tanshinone IIA (2606±478 adducts/10(9) nucleotides) and diindoylmethane (3643±469 adducts/10(9) nucleotides) were the most effective compared to vehicle treatment (14,062±1097 adducts/10(9) nucleotides). DBP is metabolized by phase I metabolizing enzymes CYP1A1, CYP1A2, and CYP1B1. DBP-induced DNA adducts can be inhibited by several mechanisms. We found that all the test agents inhibited DNA adducts by inhibiting one or more of these enzymes. Oltipraz inhibited DNA adducts entirely by inhibiting the CYP450s, while resveratrol and delphinidin inhibited DNA adducts by also interacting directly with the carcinogenic metabolite, anti-dibenzo(a,l)pyrene-11,12-dihydrodiol-13,14-epoxide. Copyright © 2015 Elsevier B.V. All rights reserved.02/2015; 774. DOI:10.1016/j.mrfmmm.2015.02.003
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ABSTRACT: Cancer, being a cause of death for major fraction of population worldwide, is one of the most studied diseases and is being investigated for the development of new technologies and more accurate therapies. Still the currently available therapies for cancer have many lacunae which affect the patient's health severely in the form of side effects. The natural drugs obtained from the medicinal plants provide a better alternative to fight against this devastating disease. Withania somnifera L. Dunal (Solanaceae), a well-known Ayurvedic medicinal plant, has been traditionally used to cure various ailments for centuries. Considering the immense potential of W. somnifera, this review provides a detail account of its vital phytoconstituents and summarizes the present status of the research carried out on its anticancerous activities, giving future directions. The sources of scientific literature were accessed from various electronic databases such as PubMed, Google Scholar, Science Direct, and library search. Various parts of W. somnifera especially the roots with its unique contents have been proved effective against different kinds of cancers. The most active components withanolides and withaferins along with a few other metabolites including withanone (WN) and withanosides have been reported effective against different types of cancer cell lines. This herb holds an important place among various anticancer medicinal plants. It is very essential to further screen and to investigate different formulations for anticancer therapy in vitro as well as in vivo in combination with established chemotherapy.Pharmaceutical Biology 04/2015; DOI:10.3109/13880209.2015.1027778 · 1.34 Impact Factor