1. Axl is a novel target of withaferin A in the induction of apoptosis and the suppression of invasion.
- Author
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Woo, Seon Min, Min, Kyoung-jin, Kim, Shin, Park, Jong-Wook, Kim, Dong Eun, Kim, Sang Hyun, Choi, Yung Hyun, and Kwon, Taeg Kyu
- Subjects
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APOPTOSIS , *CELL migration , *WITHANOLIDES , *WITHANIA somnifera , *MEDICINAL plants , *ANTINEOPLASTIC agents , *PHOSPHORYLATION - Abstract
Withaferin A, a withanolide derived from the medicinal plant Withania somnifera , has been reported to exhibit anti-tumorigenic activity against various cancer cells. In this study, we show that withaferin A inhibits the constitutive and recombinant human growth-arrest-specific protein 6 (rhGas6)-induced phosphorylation of Axl and STAT3. In addition, withaferin A also induces the down-regulation of Axl protein expression in a lysosome-dependent manner and inhibits rhGas6-induced wound healing and cell migration. Furthermore, the overexpression of Axl attenuates withaferin A-induced apoptosis. Taken together, the data from the present study indicate that the withaferin A-mediated down-regulation of the Gas6/Axl signaling pathway mediates the inhibition of cell migration and the induction of apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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