Withanone-Rich Combination of Ashwagandha Withanolides Restricts Metastasis and Angiogenesis through hnRNP-K

Ashwagandha is an important herb used in the Indian system of traditional home medicine, Ayurveda. Alcoholic extract (i-Extract) from its leaves and its component, withanone, were previously shown to possess anticancer activity. In the present study, we developed a combination of withanone and withaferin A, major withanolides in the i-Extract, that retained the selective cancer cell killing activity and found that it also has significant antimigratory, -invasive, and -angiogenic activities, in both in vitro and in vivo assays. Using bioinformatics and biochemical approaches, we demonstrate that these phytochemicals caused downregulation of migration-promoting proteins hnRNP-K, VEGF, and metalloproteases and hence are candidate natural drugs for metastatic cancer therapy. (C)2014 AACR.This work was partly supported by grants from the Ministry of Knowledge Economy, Korea (10030051) and the Korea Science and Engineering Foundation (2013K1A1A2A02050188, 2013M3A9D3045879, 2010-0029220) to C.-O. Yun and AIST, Japan Special Budget to S. C. Kaul and R. Wadhwa