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

Biochem Biophys Res Commun 2012 Oct 12;427(1):24-9. Epub 2012 Sep 12.

Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2012.08.133DOI Listing
October 2012
26 Reads

Publication Analysis

Top Keywords

withaferin a-induced
12
withaferin
9
a-induced apoptosis
8
caki cells
8
down-regulation stat3
8
human renal
8
withaferin inhibits
8
stat3
5
facs analysis
4
induced dose-dependent
4
reduction janus-activated
4
janus-activated kinase
4
analysis parp
4
jak2 activity
4
kinase jak2
4
associated reduction
4
activity withaferin
4
parp cleavage
4
overexpression stat3
4
ifn-γ-induced stat1
4

Similar Publications