Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect

Clin Cancer Res. 2007 Apr 1;13(7):2298-306. doi: 10.1158/1078-0432.CCR-06-0948.

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 with a none.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Female
  • Immunoprecipitation
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy*
  • Phytotherapy*
  • Plant Extracts / pharmacology*
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53 / drug effects*
  • Withania / chemistry*

Substances

  • Antineoplastic Agents
  • Plant Extracts
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Ashwagandha