Shinsegae Women's Hospital, Busan, Korea.
Int J Oncol. 2010 Nov;37(5):1177-85. doi: 10.3892/ijo_00000769.
Triptolide, the main active component of the traditional Chinese herbal medicine Tripterygium wilfordii Hook F, has been shown to have potent immunosuppressive and anti-inflammatory properties. Here, we investigated the pro-apoptotic effect of triptolide in human cervical cancer cells and its underlying mechanisms. Exposure of cervical cancer cells to triptolide induced apoptosis, which was accompanied by loss of mitochondrial membrane potential, caspase processing (caspase-8, -9 and -3), and cleavage of the caspase substrate, poly(ADP-ribose) polymerase. The cytotoxic effects of triptolide were significantly inhibited by the caspase inhibitor, z-VAD-fmk. Triptolide-induced apoptosis was associated with a marked reduction in Akt phosphorylation and was exacerbated by LY294002 (phosphatidylinositol-3'-kinase inhibitor). Conversely, it was attenuated by Akt overexpression. Triptolide-induced apoptosis was also associated with downregulation of Mcl-1 and was significantly inhibited by Mcl-1 overexpression. These findings show that triptolide induces caspase-dependent, mitochondria-mediated apoptosis in cervical cancer cells, in part, by negatively regulating Akt and Mcl-1.
雷公藤红素是传统中药雷公藤的主要活性成分，具有很强的免疫抑制和抗炎作用。在这里，我们研究了雷公藤红素在人宫颈癌中的促凋亡作用及其机制。雷公藤红素处理宫颈癌细胞后可诱导细胞凋亡，同时伴随着线粒体膜电位丧失、半胱氨酸天冬氨酸蛋白酶（caspase）的加工（caspase-8、-9 和 -3）以及半胱氨酸天冬氨酸蛋白酶底物聚（ADP-核糖）聚合酶的切割。半胱氨酸天冬氨酸蛋白酶抑制剂 z-VAD-fmk 显著抑制了雷公藤红素的细胞毒性作用。雷公藤红素诱导的细胞凋亡与 Akt 磷酸化的显著减少有关，并被 LY294002（磷脂酰肌醇-3'-激酶抑制剂）加重。相反，Akt 的过表达可减弱其作用。雷公藤红素诱导的凋亡还与 Mcl-1 的下调有关，Mcl-1 的过表达可显著抑制其作用。这些发现表明，雷公藤红素通过负调控 Akt 和 Mcl-1 诱导宫颈癌细胞中的 caspase 依赖性、线粒体介导的细胞凋亡。
