Song Yong Jin, Lee Dae Young, Kim Su-Nam, Lee Kang Ro, Lee Hyang Woo, Han Jeung-Whan, Kang Dong-Won, Lee Hoi Young, Kim Yong Kee
College of Medicine, Kwandong University, Gangneung 210-701, Korea.
J Pharm Pharmacol. 2005 Dec;57(12):1591-7. doi: 10.1211/jpp.57.12.0009.
Treatment with ergolide, a sesquiterpene lactone from Inula britannica var chinensis, caused the induction of apoptosis in Jurkat T cells, which was confirmed by DNA fragmentation, caspase-3 activation and cleavage of poly(ADP-ribose) polymerase in response to ergolide. Furthermore, mitochondrial dysfunction appeared to be associated with ergolide-induced apoptosis, because Bax translocation and cytochrome c release were stimulated by ergolide. In parallel, the nuclear factor-kappaB (NF-kappaB) signaling pathway was significantly inhibited by ergolide, which was accompanied by down-regulation of cell survival molecules, such as X-chromosome-linked inhibitor of apoptosis and Bcl-2. In addition, the JNK signaling pathway was involved in ergolide-induced apoptosis. Collectively, our results identified a new mechanism for the anti-cancer property of ergolide, attributable to the induction of apoptosis through down-regulation of cell survival signal molecules resulting from inhibition of the NF-kappaB signaling pathway.
旋覆花内酯是一种来自中华旋覆花的倍半萜内酯，用其进行治疗可诱导Jurkat T细胞凋亡，这通过DNA片段化、半胱天冬酶-3激活以及聚（ADP-核糖）聚合酶对旋覆花内酯的应答裂解得以证实。此外，线粒体功能障碍似乎与旋覆花内酯诱导的凋亡相关，因为旋覆花内酯可刺激Bax转位和细胞色素c释放。同时，核因子-κB（NF-κB）信号通路受到旋覆花内酯的显著抑制，这伴随着细胞存活分子如X染色体连锁凋亡抑制蛋白和Bcl-2的下调。此外，JNK信号通路参与了旋覆花内酯诱导的凋亡。总体而言，我们的结果确定了旋覆花内酯抗癌特性的一种新机制，这归因于通过抑制NF-κB信号通路导致细胞存活信号分子下调从而诱导凋亡。
