Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Basic Clin Pharmacol Toxicol. 2010 Jun;106(6):446-53. doi: 10.1111/j.1742-7843.2009.00509.x. Epub 2009 Dec 29.
The apoptotic effect of fluoxetine (FLX), an antidepressant, against human epithelial ovarian cancer cell lines OVCAR-3 and SK-OV-3 was investigated in relation to the mitochondria-mediated cell death process and nuclear factor (NF)-kappaB activation. FLX-induced mitochondrial membrane permeability change and formation of reactive oxygen species, leading to cell death. FLX-induced increase in mitochondrial Bax levels, decrease in cytosolic Bid and Bcl-2 levels, loss of the mitochondrial transmembrane potential, cytochrome c release, caspase-3 activation and up-regulation of p53. Oxidant scavengers and Bay 11-7085 [an inhibitor of nuclear factor kappaB (NF-kappaB) activation] prevented the FLX-induced cell death, increase in phosphorylated inhibitory kappaB-alpha and NF-kappaB p65 levels, and binding of NF-kappaB p65 to DNA. Results from this study suggest that FLX may exhibit apoptotic effect against ovarian cancer cell lines by inducing the mitochondrial membrane permeability change, which leads to cytochrome c release and subsequent caspase-3 activation, through reactive oxygen species-dependent activation of NF-kappaB.
研究了抗抑郁药氟西汀（FLX）对人卵巢上皮癌细胞系 OVCAR-3 和 SK-OV-3 的凋亡作用与线粒体介导的细胞死亡过程和核因子（NF）-κB 激活的关系。FLX 诱导线粒体膜通透性改变和活性氧形成，导致细胞死亡。FLX 诱导线粒体 Bax 水平增加，胞质 Bid 和 Bcl-2 水平降低，线粒体跨膜电位丧失，细胞色素 c 释放，caspase-3 激活，p53 上调。抗氧化剂清除剂和 Bay 11-7085（NF-κB 激活抑制剂）可预防 FLX 诱导的细胞死亡、磷酸化抑制κB-α和 NF-κB p65 水平增加以及 NF-κB p65 与 DNA 的结合。本研究结果表明，FLX 可能通过诱导线粒体膜通透性改变，通过活性氧依赖的 NF-κB 激活导致细胞色素 c 释放和随后的 caspase-3 激活，对卵巢癌细胞系发挥凋亡作用。
