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Autophagy. 2013 Jul;9(7):1057-68. doi: 10.4161/auto.24632. Epub 2013 Apr 18.

Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells.

Author information

1
Key Laboratory for Experimental Teratology of the Ministry of Education and School of Life Sciences; Shandong University; Jinan, China.

Abstract

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.

KEYWORDS:

MTOR; apoptosis; autophagy; endoplasmic reticulum stress; salinomycin

PMID:
23670030
PMCID:
PMC3722315
DOI:
10.4161/auto.24632
[Indexed for MEDLINE]
Free PMC Article
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