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


METHODS
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.


CONCLUSIONS
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.
Widodo
Nashi
N
Research Institute for Cell Engineering, GENE Therapeutics, Inc., National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba, Japan.
Kaur
Kamaljit
K
Shrestha
Bhupal G
BG
Takagi
Yasuomi
Y
Ishii
Tetsuro
T
Wadhwa
Renu
R
Kaul
Sunil C
SC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005260:Female; D047468:Immunoprecipitation; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects*; D032341:Withania / Q000737:chemistry*
D000970:Antineoplastic Agents; D010936:Plant Extracts; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C030693:Ashwagandha