title: Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells.
abstract: 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 1 h showed a transient elevation of the mitochondrial membrane potential (DeltaPsim), followed by cytochrome c release into the cytosol and disruption of DeltaPsim 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 rho0 counterparts confirmed a critical dependency for mitochondria during the induction of apoptosis in HepG2 cells mediated by curcumin. The effects of PEG-SOD in protecting against curcumin-induced cytotoxicity suggest that curcumin-induced cytotoxicity is directly dependent on superoxide anion O2- 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.
authors: Department of Toxicology, Dalian Medical University, Dalian 116027, China.
authors: Jun
authors: J
authors: Cao
authors: Yong
authors: Y
authors: Liu
authors: Li
authors: L
authors: Jia
authors: Hui-Min
authors: HM
authors: Zhou
authors: Ying
authors: Y
authors: Kong
authors: Guang
authors: G
authors: Yang
authors: Li-Ping
authors: LP
authors: Jiang
authors: Qiu-Juan
authors: QJ
authors: Li
authors: Lai-Fu
authors: LF
authors: Zhong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D003474:Curcumin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D016166:Free Radical Scavengers; D019253:Proto-Oncogene Proteins c-bcl-2; D013481:Superoxides; D045304:Cytochromes c; D003474:Curcumin