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: 8.72). 04/2007; 13(7):2298-306. DOI: 10.1158/1078-0432.CCR-06-0948
Source: PubMed


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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Available from: Nashi Widodo, Sep 28, 2015
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    • "Accordingly, one needs to investigate the molecular mechanism(s) of their action (cellular targets and molecular response) for their use in therapeutics. In order to investigate the cellular targets of the alcoholic extract (i-Extract) of Ashwagandha leaves, rich in Wi-A and Wi-N, we previously adopted loss-of-function screenings using siRNA and ribozyme libraries in conjugation with the cell viability assays[20,21]. These assays revealed the involvement of tumor suppressor protein p53 and oxidative stress pathways in i-Extract induced killing of cancer cells. "
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    • "The limonoids isolated from the methanol extract of Khaya Senegalensis proved good anticancer activity (Zhang et al., 2007). The leaf extract of Ashwagandha selectively killed tumor cells and thus it was a natural source for safe anticancer medicine (Widodo et al., 2007). The fruit of deerberry (Vaccinium stamineum) exhibited the anti-cancer capability of human lung and leukemia cancer cells (Wamg et al., 2007). "

    Full-text · Article · Jul 2014
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    • "Therefore, we first investigated the presence of withanone in the water extract. HPLC of ASH-WEX was performed at conditions that detected withanone and withaferin A in the alcoholic extract and as described earlier [38]. As shown in Figure 2A-2, there was neither withanone nor withaferin A in the ASH-WEX. "
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    ABSTRACT: Cancer is a leading cause of death accounting for 15-20% of global mortality. Although advancements in diagnostic and therapeutic technologies have improved cancer survival statistics, 75% of the world population live in underdeveloped regions and have poor access to the advanced medical remedies. Natural therapies hence become an alternative choice of treatment. Ashwagandha, a tropical herb used in Indian Ayurvedic medicine, has a long history of its health promoting and therapeutic effects. In the present study, we have investigated an anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX). Anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX) was detected by in vitro and in vivo assays. Bioactivity-based size fractionation and NMR analysis were performed to identify the active anticancer component(s). Mechanism of anticancer activity in the extract and its purified component was investigated by biochemical assays. We report that the ASH-WEX is cytotoxic to cancer cells selectively, and causes tumor suppression in vivo. Its active anticancer component was identified as triethylene glycol (TEG). Molecular analysis revealed activation of tumor suppressor proteins p53 and pRB by ASH-WEX and TEG in cancer cells. In contrast to the hypophosphorylation of pRB, decrease in cyclin B1 and increase in cyclin D1 in ASH-WEX and TEG-treated cancer cells (undergoing growth arrest), normal cells showed increase in pRB phosphorylation and cyclin B1, and decrease in cyclin D1 (signifying their cell cycle progression). We also found that the MMP-3 and MMP-9 that regulate metastasis were down regulated in ASH-WEX and TEG-treated cancer cells; normal cells remained unaffected. We provide the first molecular evidence that the ASH-WEX and TEG have selective cancer cell growth arrest activity and hence may offer natural and economic resources for anticancer medicine.
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