Critical roles of reactive oxygen species in mitochondrial permeability transition in mediating evodiamine-induced human melanoma A375-S2 cell apoptosis.
Previous studies have shown that evodiamine could trigger apoptosis in human malignant melanoma A375-S2 cells within 24 h. To further investigate the biochemical basis of this activity, the roles of reactive oxygen species (ROS) and mitochondrial permeability transition (MPT) were evaluated. Exposure to evodiamine led to a rapid increase in intracellular ROS followed by an onset of mitochondrial depolarization. ROS scavenger rescued the DeltaPsim dissipation and cell death induced by evodiamine, whilst MPT inhibitor blocked the second-time ROS formation as well as cell death. Expressions of key proteins in Fas- and mitochondria-mediated pathways were furthermore examined. Both pathways were activated and regulated by ROS and MPT and were converged to a final common pathway involving the activation of caspase-3. These data suggested that a phenomenon termed ROS-induced ROS release (RIRR) was involved in evodiamine-treated A375-S2 cells and greatly contributed to the apoptotic process through both extrinsic and intrinsic pathways.
Yang
Jia
J
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, PR China.
Wu
Li-Jun
LJ
Tashino
Shin-Ichi
S
Onodera
Satochi
S
Ikejima
Takashi
T
D000165:Acridine Orange / Q000494:pharmacology; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D010539:Permeability; D010936:Plant Extracts / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D017382:Reactive Oxygen Species
D010936:Plant Extracts; D011799:Quinazolines; D017382:Reactive Oxygen Species; C049639:evodiamine; D020169:Caspases; D000165:Acridine Orange