title: Trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway.
abstract: Trichothecin, one of fungal toxins which were encountered in food and in the environment, seriously threatens human and animal health. It has been shown that trichothecin changed the morphology of cellular mitochondria. However, the molecular mechanism remains unknown. Here we found that cell viability was attenuated by trichothecin. Features of apoptosis such as homosomal condensation and inter nucleosomal fragmentation were observed. In consistence with the elevated apoptosis rate, expression of anti-apoptotic protein Bcl-2 was diminished and expression of proapoptotic protein Bax was enhanced at mRNA levels. Furthermore, expression of caspase-9 and activity of caspase-3 were increased after the treatment of trichothecin. Accordingly, the mitochondrial membrane potential (∆Ψm) was decreased in a dose-dependent manner. And Ca(2+) overload was induced by trichothecin, followed by the generation of reactive oxygen species (ROS). Collectedly, our results suggested that apoptosis induced by trichothecin is mediated by caspase-9 activation and the decrement of mitochondrial function resulted from the overloaded calcium and ROS production.
authors: School of Medicine, Nanjing University, 22 Han Kou Road, Nanjing 210093, PR China.
authors: Rong Hui
authors: RH
authors: Du
authors: Jiang Tao
authors: JT
authors: Cui
authors: Ting
authors: T
authors: Wang
authors: Ai Hua
authors: AH
authors: Zhang
authors: Ren Xiang
authors: RX
authors: Tan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014255:Trichothecenes / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014255:Trichothecenes; C025711:trichothecin; D053148:Caspase 3; D053453:Caspase 9; D002118:Calcium