铁皮石斛酚 A 抑制 JAK/STAT3 信号通路并诱导人肾癌细胞 Caki 凋亡。
Withaferin A inhibits JAK/STAT3 signaling and induces apoptosis of human renal carcinoma Caki cells.
机构信息
Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
出版信息
Biochem Biophys Res Commun. 2012 Oct 12;427(1):24-9. doi: 10.1016/j.bbrc.2012.08.133. Epub 2012 Sep 12.
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.
铁皮石斛中的活性成分醉茄素 A 可诱导多种肿瘤细胞系发生细胞毒性。在本研究中，我们发现醉茄素 A 可抑制 STAT3（Tyr705 位）的组成性和 IL-6 诱导的磷酸化，但不抑制 IFN-γ诱导的 STAT1 磷酸化。醉茄素 A 诱导的 STAT3 激活下调与 Janus 激活激酶 2（JAK2）活性降低有关。醉茄素 A 还下调 STAT3 调控基因的表达，如 Bcl-xL、Bcl-2、cyclin D1 和 survivin。研究了醉茄素 A 在人肾透明细胞癌细胞系 Caki 中的凋亡作用。流式细胞术分析和 PARP 切割表明，醉茄素 A 诱导 Caki 细胞中剂量依赖性的凋亡细胞死亡。此外，STAT3 的过表达减弱了醉茄素 A 诱导的凋亡。综上所述，本研究提供了强有力的证据表明，STAT3 信号通路的下调介导了醉茄素 A 诱导的细胞凋亡。
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