ONTD inhibits the growth of human hepatoma Bel-7402 cells via a MAPK dependent mitochondrial pathway and apoptosis accompanied with the depletion of intracellular glutathione

摘要：

　　Background: ONTD, a novel synthetic triterpenoid from enoxolone, is a promising anticancer agent that has shown strong activity against a wide variety cancer types in vitro.Methods: The cytotoxic activity was evaluated by MTT assay.Flow cytometry was employed to detect mitochondrial membrane potential, apoptosis and ROS.Western blot was used to analyze signaling pathways.Results: ONTD concentration-dependently reduces Bel-7402 cells without affecting normal human liver cell line L-02 cells.ONTD-induced apoptosis of was characterized by the generation of intracellular reactive oxygen species (ROS), loss ofmitochondrial membrane potential (△Ψm), the release of apoptotic inducing factor (AlF) and cytochrome c (Cyt c) from mitochondria and cleavage of PARP-1 and procaspases-3,-9.In addition, ONTD activated the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK but not ERK1/2.Treatment with SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38) prior to ONTD markedly rescued Bel-7402 cells from ONTD-induced apoptosis.Conclusions and general significance: ONTD inhibits the growth of Bel-7402 cells through a mitochondrialmediated pathway and triggering apoptosis accompanied with the depletion of intracellular GSH.These data support development of ONTD as a potential agent for hepatocellular carcinoma therapy.

关键词： Hepatocellular carcinoma Apoptosis mitogen-activated protein kinases (MAPKs) Mitochondria ROS GSH

作者: Jiani Tan Ling Liu Tong Chen Jun Zha Linna Wang Hui Ji

作者单位: Department of Pharmacology, China Pharmaceutical University, 24 Tong Jia Xiang, 210009, Nanjing, P.R.China

会议类型: 国内会议

会议名称: 江苏省药理学会青年工作委员会成立大会暨药理学科青年科技创新学术研讨会

会议地点: 苏州

会议语种:英文

页码: 114-125

在线出版日期: 2013-05-24（万方平台首次上网日期，不代表论文的发表时间）