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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

Research Institute for Cell Engineering, GENE Therapeutics, Inc., National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba, Japan.
Clinical Cancer Research (Impact Factor: 8.19). 04/2007; 13(7):2298-306. DOI: 10.1158/1078-0432.CCR-06-0948
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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    • "Ferlay et al. (2000) reported that worldwide more than 5 million people are diagnosed with cancer and more than 3.5 million people die from cancer each year. Managing human malignancies still constitutes a major challenge for contemporary medicine (Coufal et al., 2007 and Widodo et al., 2007). Although with progress in understanding cancer biology, many new antineoplastic therapies have been developed that rely primarily on surgery, chemotherapy, radiotherapy, hormone therapy, and immunotherapeutic approaches (Khorshid et al., 2010). "
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    • "(Iuvone et al. 2003, Kaileh et al. 2007, Kuboyama et al. 2005, Widodo et al. 2007, Zhao et al. 2002 "
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