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Roots of Withania somnifera Inhibit Forestomach and Skin Carcinogenesis in Mice
Authors:Padmavathi Bandhuvula  Rath Pramod C  Rao Araga Ramesha  Singh Rana Pratap
Affiliation:1School of Life Sciences, Jawaharlal Nehru University, New Delhi, India;2Present address: Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, USA.
Abstract:We evaluated the cancer chemopreventive efficacy of the Withaniasomnifera root, which has been used in the Indian traditionalmedicine system for many centuries for the treatment of variousailments. Since, studies showing its mechanism-based cancerchemopreventive efficacy are limited, this was investigatedin the present study. We studied the effect of dietary administrationof Withania root on hepatic phase I, phase II and antioxidantenzymes by estimation of its level/activity, as well as in attenuatingcarcinogen-induced forestomach and skin tumorigenesis in theSwiss albino mouse model. Our findings showed that roots ofW.somnifera inhibit phase I, and activates phase II and antioxidantenzymes in the liver. Further, in a long-term tumorigenesisstudy, Withania inhibited benzo(a)pyrene-induced forestomachpapillomagenesis, showing up to 60 and 92% inhibition in tumorincidence and multiplicity, respectively. Similarly, Withaniainhibited 7,12-dimethylbenzanthracene-induced skin papillomagenesis,showing up to 45 and 71% inhibition in tumor incidence and multiplicity.In both studies, Withania showed no apparent toxic effects inmice as monitored by the body weight gain profile. Together,these findings suggest that W.somnifera root has chemopreventiveefficacy against forestomach and skin carcinogenesis and warrantsthe identification and isolation of active compounds responsiblefor its anticancer effects, which may provide the lead for thedevelopment of antitumor agents.
Keywords:chemoprevention - drug metabolizing enzymes - antioxidant enzymes - papillomagenesis - Withania somnifera
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