Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase
Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase
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DOI：
10.1158/0008-5472.can-06-3099
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发表时间：
2007-02-01
期刊：
影响因子：
11.2
通讯作者：
Ghafourifar, Pedram
中科院分区：
文献类型：
--
作者：
Nazarewicz, Rafal R.;Zenebe, Woineshet J.;Ghafourifar, Pedram
他莫昔芬是一种抗癌药物，通过氧化应激和一氧化氮（NO）依赖性途径诱导细胞凋亡。本报告显示，他莫昔芬增加线粒体内游离钙离子浓度和刺激线粒体NO合酶（mtNOS）的活性在大鼠肝脏和人乳腺癌MCF-7细胞的线粒体。通过刺激mtNOS，他莫昔芬阻碍线粒体呼吸，释放细胞色素c，提高线粒体脂质过氧化，增加某些线粒体蛋白的蛋白酪氨酸硝化，降低琥珀酰辅酶A：3-氧代酸辅酶A-转移酶的催化活性，并诱导线粒体聚集。本报告表明，在他莫昔芬诱导的细胞凋亡中，线粒体一氧化氮合酶起着至关重要的作用。
Tamoxifen is an anticancer drug that induces oxidative stress and apoptosis via mitochondria-dependent and nitric oxide (NO)-dependent pathways. The present report shows that tamoxifen increases intramitochondrial ionized Ca2+ concentration and stimulates mitochondrial NO synthase (mtNOS) activity in the mitochondria from rat liver and human breast cancer MCF-7 cells. By stimulating mtNOS, tamoxifen hampers mitochondrial respiration, releases cytochrome c, elevates mitochondrial lipid peroxidation, increases protein tyrosine nitration of certain mitochondrial proteins, decreases the catalytic activity of succinyl-CoA:3-oxoacid CoA-transferase, and induces aggregation of mitochondria. The present report suggests a critical role for mtNOS in apoptosis induced by tamoxifen.