Selective Killing of Cancer Cells by Leaf Extract of Ashwagandha

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

1. Nashi Widodo1,3,
2. Kamaljit Kaur1,
3. Bhupal G. Shrestha1,
4. Yasuomi Takagi2,
5. Tetsuro Ishii3,
6. Renu Wadhwa1 and
7. Sunil C. Kaul1

+ Author Affiliations

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

1. 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: [phone]; Fax: [phone]; E-mail: [e-mail].

Abstract

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.

• Medicinal plant extract
• Ashwagandha
• selective killing of cancer cells
• tumor inhibition
• mechanism
• Alternative medicine research
• Natural products
• Cellular models in prevention research
• Animal/transgenic models in promotion and prevention
• Biological and biochemical mechanisms in prevention

Footnotes

• ↵4 Cell Proliferation Reagent WST-1, a colorimetric assay for the quantification of cell proliferation and cell viability, based on the cleavage of the tetrazolium salt WST-1 by mitochondrial dihydrogenases in viable cells.

• The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

• Grant support: The study was partially supported by grants from the New Energy and Industrial Technology Development Organization (NEDO), Japan.
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