Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells
Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells
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DOI：
10.1016/j.lfs.2006.06.044
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发表时间：
2006-10-19
期刊：
影响因子：
6.1
通讯作者：
Ito, Susumu
中科院分区：
文献类型：
--
作者：
Cheng, Xinliang;Shimizu, Ichiro;Ito, Susumu
氧化应激，包括活性氧（ROS）的产生，是已知的参与细胞凋亡。因此，阻止细胞凋亡可诱导肝肿瘤细胞的恶性转化。雌二醇（E2）是一种有效的内源性抗氧化剂。我们研究了孕激素的促凋亡作用以及E2在肿瘤坏死因子（TNF）α诱导的早期凋亡状态下的人肝癌HuH-7细胞中的抗凋亡作用。E2抑制了TNF α诱导的活性氧产生、脂质过氧化、抗氧化酶消耗、Bcl-2家族蛋白的促凋亡优势表达以及线粒体膜电位的破坏，然后在HuH-7细胞中进一步受到黄体酮的刺激。E2的抑制作用可被孕酮阻断。孕酮受体拮抗剂RU 486的治疗导致阻断，孕酮介导的反应，E2预处理TNF α诱导的细胞凋亡。这些结果表明，E2抑制TNF α诱导的肝癌细胞的早期凋亡，通过抑制氧化应激过程，而孕酮的作用方式与E2的作用相反，E2的抑制作用被孕酮阻断，从而导致肝癌细胞的凋亡。(c)2006年爱思唯尔公司All rights reserved.
Oxidative stress, including the generation of reactive oxygen species (ROS), is known to be involved in apoptosis. Preventing apoptosis may thereby induce a malignant transformation of liver tumor cells. Estradiol (E2) is a potent endogenous antioxidant. We examined the proapoptotic role of progesterone as well as the antiapoptotic role of E2 in human hepatoma HuH-7 cells in a state of early apoptosis induced by tumor necrosis factor (TNF) alpha. The TNF alpha-induced ROS generation, lipid peroxidation, antioxidant enzyme consumption, a proapoptotic predominant expression of Bcl-2 family proteins, and a disruption of mitochondrial membrane potential were all inhibited by E2, and then they were further stimulated by progesterone in HuH-7 cells. The inhibitory effects of E2 were blocked by coincubation with progesterone. Treatment with the progesterone receptor antagonist RU486 led to the blockage of the, progesterone-mediated responses to E2 pretreatment in TNF alpha-induced apoptosis. These findings demonstrate that E2 inhibits the TNF alpha-induced early apoptosis in hepatoma cells, by suppressing the oxidative stress processes, whereas progesterone acts in a manner opposite from the effects of E2, and the inhibitory effects of E2 were blocked by progesterone, thus leading to the apoptosis of hepatoma cells. (c) 2006 Elsevier Inc. All rights reserved.