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eCAM Advance Access published online on February 9, 2005

eCAM, doi:10.1093/ecam/neh064
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© The Author (2005). Published by Oxford University Press. All rights reserved.
Received June 27, 2004
Revised December 17, 2004
Accepted January 10, 2005

Original Article

Roots of Withania somnifera Inhibit Forestomach and Skin Carcinogenesis in Mice

Bandhuvula Padmavathi 1, Pramod C. Rath 1, Araga Ramesha Rao 1, and Rana Pratap Singh 1*

1 School of Life Sciences, Jawaharlal Nehru University, New Delhi, India

* To whom correspondence should be addressed.
Rana Pratap Singh, E-mail: Rana.Singh{at}UCHSC.edu


   Abstract

We evaluated the cancer chemopreventive efficacy of the Withania somnifera root, which has been used in the Indian traditional medicine system for many centuries for the treatment of various ailments. Since, studies showing its mechanism-based cancer chemopreventive efficacy are limited, this was investigated in the present study. We studied the effect of dietary administration of Withania root on hepatic phase I, phase II and antioxidant enzymes by estimation of its level/activity, as well as in attenuating carcinogen- induced forestomach and skin tumorigenesis in the Swiss albino mouse model. Our findings showed that roots of W.somnifera inhibit phase I, and activates phase II and antioxidant enzymes in the liver. Further, in a long-term tumorigenesis study, Withania inhibited benzo(a)pyrene-induced forestomach papillomagenesis, showing up to 60 and 92% inhibition in tumor incidence and multiplicity, respectively. Similarly, Withania inhibited 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 in mice as monitored by the body weight gain profile. Together, these findings suggest that W.somnifera root has chemopreventive efficacy against forestomach and skin carcinogenesis and warrants the identification and isolation of active compounds responsible for its anticancer effects, which may provide the lead for the development of antitumor agents.

Keywords: chemoprevention; drug metabolizing enzymes; antioxidant enzymes; papillomagenesis; Withania somnifera.
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