Atmospheric gas plasma-induced ROS production activates TNF-ASK1 pathway for the induction of melanoma cancer cell apoptosis.
Atmospheric gas plasma-induced ROS production activates TNF-ASK1 pathway for the induction of melanoma cancer cell apoptosis.
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DOI：
10.1091/mbc.e13-10-0590
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发表时间：
2014-05
影响因子：
3.3
通讯作者：
Ostrikov K
中科院分区：
文献类型：
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作者：
Ishaq M;Kumar S;Varinli H;Han ZJ;Rider AE;Evans MD;Murphy AB;Ostrikov K
大气等离子体 (AGP) 上调细胞内 ROS 水平并诱导黑色素瘤细胞凋亡。 ASK1 介导的细胞凋亡依赖 TNF 信号的证据表明，肿瘤细胞中 AGP 激活和细胞凋亡信号通路调节的可能机制。大气等离子体（AGP）能够选择性地诱导癌细胞凋亡，为具有耐药性和毒性等不良副作用的传统疗法提供了一种有前景的替代方案。然而，AGP 诱导癌细胞死亡的机制尚不清楚。在这项研究中，AGP 被证明可以上调细胞内活性氧 (ROS) 水平并诱导黑色素瘤细胞凋亡，但不能诱导正常黑色素细胞凋亡。通过筛选参与细胞凋亡的基因，我们确定肿瘤坏死因子 (TNF) 家族成员是 AGP 处理黑色素瘤细胞后表达差异最大的细胞基因。 TNF 受体 1 (TNFR1) 拮抗剂 - 中和抗体特异性抑制 AGP 诱导的细胞凋亡信号，调节细胞凋亡信号 - 调节激酶 1 (ASK1) 活性和随后的 ASK1 依赖性细胞凋亡。用细胞内 ROS 清除剂 N-乙酰基-L-半胱氨酸处理细胞也会抑制 AGP 诱导的 ASK1 激活以及细胞凋亡。此外，细胞内 ASK1 的消耗降低了 AGP 诱导的氧化应激和细胞凋亡的水平。 ASK1 介导的细胞凋亡依赖 TNF 信号的证据表明肿瘤细胞中 AGP 激活和细胞凋亡信号通路调节的可能机制。
Atmospheric gas plasmas (AGPs) up-regulate intracellular ROS levels and induce apoptosis in melanoma cells. Evidence for TNF-signaling dependence of ASK1-mediated apoptosis suggests possible mechanisms for AGP activation and regulation of apoptosis-signaling pathways in tumor cells. Atmospheric gas plasmas (AGPs) are able to selectively induce apoptosis in cancer cells, offering a promising alternative to conventional therapies that have unwanted side effects such as drug resistance and toxicity. However, the mechanism of AGP-induced cancer cell death is unknown. In this study, AGP is shown to up-regulate intracellular reactive oxygen species (ROS) levels and induce apoptosis in melanoma but not normal melanocyte cells. By screening genes involved in apoptosis, we identify tumor necrosis factor (TNF)–family members as the most differentially expressed cellular genes upon AGP treatment of melanoma cells. TNF receptor 1 (TNFR1) antagonist–neutralizing antibody specifically inhibits AGP-induced apoptosis signal, regulating apoptosis signal–regulating kinase 1 (ASK1) activity and subsequent ASK1-dependent apoptosis. Treatment of cells with intracellular ROS scavenger N-acetyl-l-cysteine also inhibits AGP-induced activation of ASK1, as well as apoptosis. Moreover, depletion of intracellular ASK1 reduces the level of AGP-induced oxidative stress and apoptosis. The evidence for TNF-signaling dependence of ASK1-mediated apoptosis suggests possible mechanisms for AGP activation and regulation of apoptosis-signaling pathways in tumor cells.