Withanone-rich combination of Ashwagandha withanolides restricts metastasis and angiogenesis through hnRNP-K

• Published in: Molecular cancer therapeutics Vol. 13; no. 12; pp. 2930 - 2940
• Main Authors: Gao, Ran, Shah, Navjot, Lee, Jung-Sun, Katiyar, Shashank P, Li, Ling, Oh, Eonju, Sundar, Durai, Yun, Chae-Ok, Wadhwa, Renu, Kaul, Sunil C
• Format: Journal Article
• Language: English
• Published: United States 01.12.2014
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Disease Models, Animal; Heterogeneous-Nuclear Ribonucleoprotein K - antagonists & inhibitors; Heterogeneous-Nuclear Ribonucleoprotein K - chemistry; Heterogeneous-Nuclear Ribonucleoprotein K - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Mice; Models, Molecular; Molecular Conformation; Neoplasm Metastasis; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Neovascularization, Pathologic - metabolism; Plant Extracts - chemistry; Reproducibility of Results; Triterpenes - chemistry; Triterpenes - pharmacology; Tumor Burden - drug effects; Withanolides - chemistry; Withanolides - pharmacology; Xenograft Model Antitumor Assays
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.mct-14-0324

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.