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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)455-460
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume451
Issue number3
DOIs
StatePublished - 29 Aug 2014

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