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Selective Killing of Cancer Cells by Leaf Extract of Ashwagandha: Identification of a Tumor-Inhibitory Factor and the First Molecular Insights to Its Effect

Authors' Affiliations: ¹ Research Institute for Cell Engineering, ² GENE Therapeutics, Inc., National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba; and ³ Department of Molecular and Cellular Physiology, University of Tsukuba, Ibaraki, Japan

Requests for reprints: Renu Wadhwa, National Institute of Advanced Industrial Science and Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan. Phone: 81-29-861-9464; Fax: 81-29-861-2900; E-mail: renu-wadhwa{at}aist.go.jp.

Purpose: Ashwagandha is regarded as a wonder shrub of India and is commonly used in Ayurvedic medicine and health tonics that claim its variety of health-promoting effects. Surprisingly, these claims are not well supported by adequate studies, and the molecular mechanisms of its action remain largely unexplored to date. We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha.

Experimental Design: Selective tumor-inhibitory activity of the leaf extract (i-Extract) was identified by in vivo tumor formation assays in nude mice and by in vitro growth assays of normal and human transformed cells. To investigate the cellular targets of i-Extract, we adopted a gene silencing approach using a selected small hairpin RNA library and found that p53 is required for the killing activity of i-Extract.

Results: By molecular analysis of p53 function in normal and a variety of tumor cells, we found that it is selectively activated in tumor cells, causing either their growth arrest or apoptosis. By fractionation, purification, and structural analysis of the i-Extract constituents, we have identified its p53-activating tumor-inhibiting factor as withanone.

Conclusion: We provide the first molecular evidence that the leaf extract of ashwagandha selectively kills tumor cells and, thus, is a natural source for safe anticancer medicine.