Critical roles of reactive oxygen species in mitochondrial permeability transition in mediating evodiamine-induced human melanoma A375-S2 cell apoptosis
Critical roles of reactive oxygen species in mitochondrial permeability transition in mediating evodiamine-induced human melanoma A375-S2 cell apoptosis
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DOI：
10.1080/10715760701499356
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Ikejima, Takashi
中科院分区：
文献类型：
--
作者：
Yang, Jia;Wu, Li-Jun;Ikejima, Takashi
已有研究表明，吴茱萸碱可在24 h内诱导人恶性黑色素瘤A375-S2细胞凋亡。为了进一步研究这种活性的生化基础，活性氧（ROS）和线粒体通透性转换（MPT）的作用进行了评估。暴露于吴茱萸碱导致细胞内ROS迅速增加，随后发生线粒体去极化。活性氧清除剂可抑制吴茱萸碱诱导的Δ Psi m耗散和细胞死亡，而MPT抑制剂可阻断二次活性氧形成和细胞死亡。进一步检测Fas和Fas介导途径中关键蛋白的表达。这两条途径都被ROS和MPT激活和调节，并最终汇聚成一条涉及caspase-3激活的共同途径。这些数据表明，一种被称为ROS诱导的ROS释放（RIRR）的现象参与了吴茱萸碱处理的A375-S2细胞，并通过外源性和内源性途径极大地促进了凋亡过程。
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 Delta Psi m 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.