Axl is a novel target of withaferin A in the induction of apoptosis
and the suppression of invasion
- Seon Min Woo; Kyoung-jin Min; Shin Kim; Jong-Wook Park; Dong Eun Kim; Sang Hyun Kim; Yung Hyun Choi; Taeg Kyu Kwon
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- 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.
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