Axl is a novel target of withaferin A in the induction of apoptosis and the suppression of invasion

Biochem Biophys Res Commun. 2014 Aug 29;451(3):455-60. doi: 10.1016/j.bbrc.2014.08.018. Epub 2014 Aug 9.

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.

Keywords: Apoptosis; Axl; Gas6; Migration; Withaferin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Axl Receptor Tyrosine Kinase
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Down-Regulation
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Phosphorylation
  • Proto-Oncogene Proteins / drug effects*
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / drug effects*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • STAT3 Transcription Factor / physiology
  • Signal Transduction / drug effects
  • Withanolides / pharmacology*
  • Wound Healing / drug effects

Substances

  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • STAT3 Transcription Factor
  • Withanolides
  • growth arrest-specific protein 6
  • Receptor Protein-Tyrosine Kinases
  • withaferin A
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human