Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells.
Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells.
复制标题
盐霉素通过激活人类癌细胞的内质网应激，通过自噬诱导细胞死亡
作者：
Li T;Su L;Zhong N;Hao X;Zhong D;Singhal S;Liu X
盐霉素可能是第一个通过高通量筛选癌症干细胞发现的有前途的化合物。这种新型药物可以选择性地消除乳腺癌和其他癌症干细胞，尽管其作用机制尚不清楚。在这项研究中，我们发现盐霉素诱导人非小细胞肺癌（NSCLC）细胞自噬。此外，我们证明盐霉素刺激内质网应激并通过ATF 4-DDIT 3/CHOP-TRIB 3-AKT 1-MTOR轴介导自噬。此外，我们发现盐霉素诱导的自噬在人NSCLC细胞中发挥了促生存作用，并减弱了凋亡级联反应。我们还发现，盐霉素在CDH 1表达受到抑制的A549细胞中引发了更多的凋亡和更少的自噬，这表明抑制自噬可能是靶向癌症干细胞的有希望的策略。总之，这些研究结果提供了证据表明，盐霉素和药理学自噬抑制剂的联合治疗将是消除癌细胞以及癌症干细胞的有效治疗策略。
Salinomycin is perhaps the first promising compound that was discovered through high throughput screening in cancer stem cells. This novel agent can selectively eliminate breast and other cancer stem cells, though the mechanism of action remains unclear. In this study, we found that salinomycin induced autophagy in human non-small cell lung cancer (NSCLC) cells. Furthermore, we demonstrated that salinomycin stimulated endoplasmic reticulum stress and mediated autophagy via the ATF4-DDIT3/CHOP-TRIB3-AKT1-MTOR axis. Moreover, we found that the autophagy induced by salinomycin played a prosurvival role in human NSCLC cells and attenuated the apoptotic cascade. We also showed that salinomycin triggered more apoptosis and less autophagy in A549 cells in which CDH1 expression was inhibited, suggesting that the inhibition of autophagy might represent a promising strategy to target cancer stem cells. In conclusion, these findings provide evidence that combination treatment with salinomycin and pharmacological autophagy inhibitors will be an effective therapeutic strategy for eliminating cancer cells as well as cancer stem cells.
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DOI：
10.1158/1940-6207.capr-10-0387
发表时间：
2011-07
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Chen HY;White E
通讯作者：
White E
影响因子：
2.6
作者：
Daugschies, A;Gasslein, U;Rommel, M
通讯作者：
Rommel, M
影响因子：
7.3
作者：
Kim, Ju-Hwa;Chae, Minji;Yoon, Sungpil
通讯作者：
Yoon, Sungpil
影响因子：
16
作者：
Kroemer G;Mariño G;Levine B
通讯作者：
Levine B
影响因子：
11.2
作者：
Liu, Xiangguo;Yue, Ping;Sun, Shi-Yong
通讯作者：
Sun, Shi-Yong