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

doi:10.1016/j.bbrc.2014.08.018

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 journal › Article › peer-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 language	English
Pages (from-to)	455-460
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	451
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2014.08.018
State	Published - 29 Aug 2014

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10.1016/j.bbrc.2014.08.018

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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.",

author = "Woo, \{Seon Min\} and Min, \{Kyoung Jin\} and Shin Kim and Park, \{Jong Wook\} and Kim, \{Dong Eun\} and Kim, \{Sang Hyun\} and Choi, \{Yung Hyun\} and Kwon, \{Taeg Kyu\}",

year = "2014",

month = aug,

day = "29",

doi = "10.1016/j.bbrc.2014.08.018",

language = "English",

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pages = "455--460",

journal = "Biochemical and Biophysical Research Communications",

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TY - JOUR

T1 - Axl is a novel target of withaferin A in the induction of apoptosis and the suppression of invasion

AU - Woo, Seon Min

AU - Min, Kyoung Jin

AU - Kim, Shin

AU - Park, Jong Wook

AU - Kim, Dong Eun

AU - Kim, Sang Hyun

AU - Choi, Yung Hyun

AU - Kwon, Taeg Kyu

PY - 2014/8/29

Y1 - 2014/8/29

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84908373375

U2 - 10.1016/j.bbrc.2014.08.018

DO - 10.1016/j.bbrc.2014.08.018

M3 - Article

C2 - 25117439

AN - SCOPUS:84908373375

SN - 0006-291X

VL - 451

SP - 455

EP - 460

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

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

Abstract

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