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Withaferin A inhibits JAK/STAT3 signaling and induces apoptosis of human renal carcinoma Caki cells

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Author(s)
권택규김동은
Alternative Author(s)
Kwon, Taeg KyuKim, Dong Eun
Publication Year
2012
Abstract
Withaferin A, the active component of Withania somnifera, causes cytotoxicity in a variety of tumor cell lines. In this study, we show that withaferin A inhibits constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705), but not IFN-γ-induced STAT1 phosphorylation. Withaferin A-induced down-regulation of STAT3 activation is associated with a reduction in Janus-activated kinase 2 (JAK2) activity. Withaferin A also down-regulates the expression of STAT3 regulated genes such as Bcl-xL, Bcl-2, cyclin D1 and survivin. The apoptotic effect of withaferin A in Caki human renal cancer cells was investigated. Withaferin A induced dose-dependent apoptotic cell death in Caki cells, as measured by FACS analysis and PARP cleavage. Furthermore, overexpression of STAT3 attenuated withaferin A-induced apoptosis. Taken together, the present study provides strong evidence that down-regulation of the STAT3 signaling pathway mediates withaferin A-induced apoptosis.
Department
Dept. of Immunology (면역학)
Dept. of Otorhinolaryngology (이비인후과학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.427(1) : 24-29, 2012
Type
Article
ISSN
0006-291X
DOI
10.1016/j.bbrc.2012.08.133
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35204
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