title: Axl is a novel target of withaferin A in the induction of apoptosis and the suppression of invasion.
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.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
authors.forename: Seon Min
authors.initials: SM
authors.lastname: Woo
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
authors.forename: Kyoung-jin
authors.initials: KJ
authors.lastname: Min
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Otolaryngology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Kim
authors.affiliation: Deaprtment of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, South Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea. Electronic address: kwontk@dsmc.or.kr.
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D054358:Withanolides / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D050796:STAT3 Transcription Factor; D054358:Withanolides; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C009684:withaferin A; C000722289:AXL protein, human
keywords: Apoptosis; Axl; Gas6; Migration; Withaferin A