Rapamycin suppresses ROS-dependent apoptosis caused by selenomethionine in A549 lung carcinoma cells
Rapamycin suppresses ROS-dependent apoptosis caused by selenomethionine in A549 lung carcinoma cells
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DOI：
10.1007/s00280-010-1417-7
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发表时间：
2011-05
影响因子：
3
通讯作者：
Maiko Suzuki;Manabu Endo;F. Shinohara;S. Echigo;H. Rikiishi
中科院分区：
文献类型：
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作者：
Maiko Suzuki;Manabu Endo;F. Shinohara;S. Echigo;H. Rikiishi
目的硒化合物具有诱导癌细胞凋亡的化疗作用，对正常细胞无明显毒副作用，但其抗肿瘤作用的机制尚不清楚。在这项研究中，我们研究了雷帕霉素对硒-L-蛋氨酸（SeMet）或亚硒酸盐诱导的A549细胞凋亡的影响。方法研究了硒化合物SeMet和亚硒酸盐对人腺癌细胞系（A549）增殖、凋亡及其信号通路的影响。在不同时期用每种Se处理癌细胞。细胞凋亡和信号分子进行了分析，通过流式细胞术（TUNEL法）或免疫blotting.ResultsSeMet诱导活性氧的产生与诱导细胞凋亡，因为预处理的细胞与N-乙酰-L-半胱氨酸完全阻断SeMet诱导的细胞凋亡。我们还发现，雷帕霉素完全抑制了SeMet处理的细胞凋亡，而不是亚硒酸盐。SeMet诱导的细胞凋亡与PI 3 K家族抑制剂（LY 294002、渥曼青霉素、PI-103和3-甲基腺嘌呤）组合显著下调。此外，ROS的产生包括在下游信号事件与mTOR的磷酸化，因为雷帕霉素预处理的细胞抑制ROS generation.ConclusionThese结果表明，SeMet诱导的A549细胞凋亡的Akt/mTOR/ROS通路的影响。Akt在SeMet处理的肺癌细胞系统中具有抗存活功能，但自噬信号转导仍然未解决。
PurposeAlthough selenium compounds possess chemotherapeutic features by inducing apoptosis in cancer cells with trivial side effects on normal cells, the mechanisms underlying its anti-cancer activity are insufficiently understood at the present. In this study, we investigated the effects of rapamycin on apoptosis induced by seleno-L-methionine (SeMet) or selenite in A549 cells.MethodsThe effects of Se compounds, SeMet and selenite, on cell proliferation, apoptosis and its signaling pathway were investigated in established human adenocarcinoma cell line (A549). Cancer cells were treated with each Se during different periods. Cell apoptosis and signaling molecules were analyzed by flow cytometry (TUNEL method) or immunoblotting, respectively.ResultsSeMet induces reactive oxygen species generation associated with the induction of apoptosis, because pretreatment of cells with N-acetyl-L-cysteine completely blocked SeMet-induced apoptosis. We also found that rapamycin completely suppressed the apoptosis of cells treated by SeMet, but not selenite. SeMet-induced apoptosis is significantly downregulated in combination with PI3 K family inhibitors (LY294002, wortmannin, PI-103, and 3-methyladenine). In addition, ROS generation was included in downstream signaling events associated with the phosphorylation of mTOR, because pretreatment of cells with rapamycin inhibited ROS generation.ConclusionThese results suggest that SeMet-induced apoptosis is affected by the Akt/mTOR/ROS pathway in A549 cells. Akt serves an anti-survival function in the system of SeMet-treated lung cancer cells, but autophagic signaling remained unsolved.