Mitochondrial reactive oxygen species affect sensitivity to curcumin-induced apoptosis.
Curcumin exhibits anticancer activity in vivo and triggers tumor cell apoptosis in vivo and in vitro. Several in vitro studies suggest that curcumin-induced apoptosis is associated with reactive oxygen species (ROS) production and/or oxidative stress in transformed cells. This study compared and contrasted the effects of curcumin on human skin cancer cells and their respiration-deficient (rho0) clones to characterize the prospective oxidative stress signaling responsible for initiating apoptosis. Curcumin promoted a dose-and time-dependent G2/M cell cycle arrest and/or apoptosis in COLO 16 cells. Apoptosis induction in COLO 16 cells was associated with DNA fragmentation, cell shrinkage, the externalization of cell membrane phosphatidylserine, and mitochondrial disruption, which were preceded by an increase in intracellular ROS production. Pharmacologically lowering the mitochondrial bioenergetic capacity, as well as the constitutive ROS levels, in COLO 16 cells suppressed the cytotoxic effects of curcumin. Correspondingly, the rho0 counterparts of COLO 16 cells were markedly resistant to ROS production, mitochondrial disruption, and DNA fragmentation following curcumin exposure. These observations implied that the diminution of mitochondrial ROS production protected cells against the cytotoxic effects of curcumin, and support the notion that mitochondrial respiration and redox tone are pivotal determinants in apoptosis signaling by curcumin in human skin cancer cells.
Hail
Numsen
N
Department of Pharmaceutical Sciences, The University of Colorado Denver School of Pharmacy, Denver, CO 80220, USA. Numsen.Hail@UCHSC.edu
D017209:Apoptosis; D002453:Cell Cycle; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D010101:Oxygen Consumption; D010718:Phosphatidylserines / Q000737:chemistry; D017382:Reactive Oxygen Species; D013997:Time Factors
D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D003474:Curcumin