Department of Herbal Resources, Professional Graduate School of Oriental Medicine, Wonkwang University, Republic of Korea.
Evid Based Complement Alternat Med. 2012;2012:981675. doi: 10.1155/2012/981675. Epub 2012 Jun 6.
Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a precursor of various synthetic steroidal drugs. Diosgenin is studied for the mechanism of its action in apoptotic pathway in human hepatocellular carcinoma cells. Based on DAPI staining, diosgenin-treated cells manifested nuclear shrinkage, condensation, and fragmentation. Treatment of HepG2 cells with 40 μM diosgenin resulted in activation of the caspase-3, -8, -9 and cleavage of poly-ADP-ribose polymerase (PARP) and the release of cytochrome c. In the upstream, diosgenin increased the expression of Bax, decreased the expression of Bid and Bcl-2, and augmented the Bax/Bcl-2 ratio. Diosgenin-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of JNK, p38 MAPK and apoptosis signal-regulating kinase (ASK)-1, as well as generation of the ROS. NAC administration, a scavenger of ROS, reversed diosgene-induced cell death. These results suggest that diosgenin-induced apoptosis in HepG2 cells through Bcl-2 protein family-mediated mitochndria/caspase-3-dependent pathway. Also, diosgenin strongly generated ROS and this oxidative stress might induce apoptosis through activation of ASK1, which are critical upstream signals for JNK/p38 MAPK activation in HepG2 cancer cells.
薯蓣皂苷元是一种天然存在的甾体皂苷，在豆类和山药中含量丰富，是各种合成甾体药物的前体。薯蓣皂苷元因其在人肝癌细胞凋亡途径中的作用机制而受到研究。基于 DAPI 染色，薯蓣皂苷元处理的细胞表现出核收缩、浓缩和碎裂。用 40 μM 薯蓣皂苷元处理 HepG2 细胞导致 caspase-3、-8、-9 的激活和多聚 ADP-核糖聚合酶（PARP）的切割以及细胞色素 c 的释放。在上游，薯蓣皂苷元增加了 Bax 的表达，降低了 Bid 和 Bcl-2 的表达，并增加了 Bax/Bcl-2 比值。薯蓣皂苷元诱导的、剂量依赖性的细胞凋亡伴随着 JNK、p38 MAPK 和凋亡信号调节激酶（ASK）-1 的持续磷酸化以及 ROS 的产生。ROS 清除剂 NAC 的给药逆转了薯蓣皂苷元诱导的细胞死亡。这些结果表明，薯蓣皂苷元通过 Bcl-2 蛋白家族介导的线粒体/ caspase-3 依赖性途径诱导 HepG2 细胞凋亡。此外，薯蓣皂苷元强烈产生 ROS，这种氧化应激可能通过激活 ASK1 诱导细胞凋亡，ASK1 是 HepG2 癌细胞中 JNK/p38 MAPK 激活的关键上游信号。
