Wuhan University, China.
Biochem Pharmacol. 2010 Jul 15;80(2):247-54. doi: 10.1016/j.bcp.2010.03.021. Epub 2010 Mar 25.
In this study, the apoptotic effect of alpha-bisabolol, a sesquiterpene, against human liver carcinoma cell line HepG2 was investigated. MTT assay showed alpha-bisabolol could effectively induce cytotoxicity in several human cancer cell lines (PC-3, Hela, ECA-109 and HepG2). The results of nuclei morphology examination, DNA fragmentation detection, flow cytometry analysis and cleavage of poly(ADP-ribose) polymerase and caspases indicated alpha-bisabolol might induce dose- and time-dependent apoptosis in HepG2 cells. Western blot data also showed a cascade activation of caspases-8,-9,-3 and promoted expression of Fas, implying caspase-8 might function as an upstream regulator, and the Fas-related pathway might be involved in this process. Preparation of mitochondrial/cytosol fraction followed with immunoblot analysis showed the release of chromosome c from mitochondria, down-regulated expression of Bcl-2 and translocation of Bax, Bak and Bid, suggesting the mitochondrial-related pathway might be involved in alpha-bisabolol-induced apoptosis either. Detection of accumulation of nuclear wild-type p53 and up-regulated expression of NFkappaB indicated these two key regulator with transcriptional decision-making function in various signaling pathways might also play a role in alpha-bisabolol-induced apoptosis in HepG2 cells.
在这项研究中，我们研究了倍半萜烯化合物 α- 姜黄烯对人肝癌细胞系 HepG2 的凋亡作用。MTT 检测结果表明，α- 姜黄烯能有效诱导多种人类癌细胞系（PC-3、Hela、ECA-109 和 HepG2）的细胞毒性。细胞核形态检查、DNA 片段化检测、流式细胞术分析和多聚（ADP-核糖）聚合酶和胱天蛋白酶的切割结果表明，α- 姜黄烯可能在 HepG2 细胞中诱导剂量和时间依赖性凋亡。Western blot 数据还显示 caspase-8、caspase-9、caspase-3 的级联激活和 Fas 的表达促进，提示 caspase-8 可能作为上游调节剂发挥作用，Fas 相关途径可能参与这一过程。线粒体/胞浆部分的制备和免疫印迹分析显示，染色体 c 从线粒体中释放，Bcl-2 表达下调，Bax、Bak 和 Bid 易位，提示线粒体相关途径可能参与 α- 姜黄烯诱导的 HepG2 细胞凋亡。核野生型 p53 的积累和 NFkappaB 的上调表达表明，这两个具有转录决策功能的关键调节因子在各种信号通路中也可能在 α- 姜黄烯诱导的 HepG2 细胞凋亡中发挥作用。
