Curcurnin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells

被引:172
作者
Cao, Jun
Liu, Yong
Jia, Li
Zhou, Hui-Min
Kong, Ying
Yang, Guang
Jiang, Li-Ping
Li, Qiu-Juan
Zhong, Lai-Fu [1 ]
机构
[1] Dalian Med Univ, Dept Toxicol, Dalian 116027, Peoples R China
[2] Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
[3] Dalian Med Univ, Coll Lab Med, Dalian 116027, Peoples R China
[4] Dalian Med Univ, Dept Microbiol, Dalian 116027, Peoples R China
[5] Dalian Med Univ, Dept Biochem & Mol Biol, Dalian 116027, Peoples R China
关键词
curcumin; mitochondrial hyperpolarization; mitochondrial DNA damage; apoptosis; HepG2; cells; free radicals;
D O I
10.1016/j.freeradbiomed.2007.06.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Curcumin, a major pigment of turmeric, is a natural antioxidant possessing a variety of pharmacological activities and therapeutic properties. But its mechanisms are unknown. In our previous study, we found that a 2-h exposure to curcumin induced DNA damage to both the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA) in HepG2 cells and that mtDNA damage was more extensive than nDNA damage. Therefore, experiments were initiated to evaluate the role of mtDNA damage in curcumin-induced apoptosis. The results demonstrated that HepG2 cells challenged with curcumin for I It showed a transient elevation of the mitochondrial membrane potential (Delta Psi(m)), followed by cytochrome c release into the cytosol and disruption of after 6 h exposure to curcumin. Apoptosis was detected by Hoechst 33342 and annexin V/PI assay after 10 h treatment. Interestingly, the expression of Bcl-2 remained unchanged. A resistance to apoptosis for the corresponding p(0) counterparts confirmed a critical dependency for mitochondria during the induction of apoptosis in HepG2 cells mediated by curcumin. The effects of PEGSOD in protecting against curcumin -induced cytotoxicity suggest that curcumin-induced cytotoxicity is directly dependent on superoxide anion O-2(-) production. These data suggest that mitochondrial hyperpolarization is a prerequisite for curcumin -induced apoptosis and that mtDNA damage is the initial event triggering a chain of events leading to apoptosis in HepG2 cells. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:968 / 975
页数:8
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