Reactive oxygen species-mitochondria pathway involved in LYG-202-induced apoptosis in human hepatocellular carcinoma HepG2 cells

被引：64

作者：

Chen, Fei-hong ^{[1
]}

Zhang, Lin-bo ^{[1
]}

Qiang, Lei ^{[1
]}

Yang, Zhen ^{[1
]}

Wu, Tian ^{[1
]}

Zou, Mei-juan ^{[1
]}

Tao, Lei ^{[1
]}

You, Qi-dong ^{[1
]}

Li, Zhi-yu ^{[1
]}

Yang, Yong ^{[1
]}

Guo, Qing-Long ^{[1
]}

机构：

[1] China Pharmaceut Univ, Jiangsu Key Lab Carcinogenesis & Intervent, Nanjing 210009, Peoples R China

来源：

CANCER LETTERS | 2010年 / 296卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Apoptosis; MAPK; Mitochondria; MMP; ROS; CANCER-CELLS; DEATH; ROS; KINASE; DEPOLARIZATION; ACTIVATION; INDUCTION; DECREASE; GROWTH;

D O I：

10.1016/j.canlet.2010.04.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Previously, we demonstrated that LYG-202, a newly synthesized flavonoid with a piperazine substitution, exhibited obvious antitumor activity in vivo and in vitro. The exact mechanism of this new compound remains unclear. In the present study, we examined the effects of LYG-202 on reactive oxygen species (ROS) production and the downstream signaling pathway in the apoptosis of human hepatocellular carcinoma HepG2 cells. Pretreatment with NAC (N-acetylcysteine), a ROS production inhibitor, partly inhibited the apoptosis induced by LYG-202 via blocking the ROS generation. Further data revealed that LYG-202 induced ROS accumulation followed by a decrease in mitochondrial membrane potential (MMP), release of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) to cytosol, which induced apoptosis of the cells. Moreover, the mitogen-activated protein kinases (MAPK), the downstream effect of ROS accumulation including c-Jun N-terminal kinase (JNK) and p38 MAPK, could be activated by LYG-202. Taken together, the generation of ROS might play an important role in LYG-202-induced mitochondrial apoptosis pathway, which provided further support for LYG-202 as a novel anticancer therapeutic candidate. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：96 / 105

页数：10

共 27 条

[1]

Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytes [J].