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Oncol Rep. 2017 Jun;37(6):3321-3328. doi: 10.3892/or.2017.5615. Epub 2017 May 2.

Salinomycin induces endoplasmic reticulum stress‑mediated autophagy and apoptosis through generation of reactive oxygen species in human glioma U87MG cells.

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Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Department of Herbal Formula, Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
Genome Instability Research, Ajou University School of Medicine, Suwon 16502, Republic of Korea.
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University, Yangsan 50612, Republic of Korea.


Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell apoptosis in human cancer cells displaying multiple mechanisms of drug resistance. In the present study, we explored the impact of salinomycin on the apoptosis and autophagy as well as the correlation between those effects and endoplasmic reticulum (ER) stress molecular mechanisms in human glioma U87MG cells. Apoptosis, autophagy and reactive oxygen species (ROS) were analyzed using flow cytometry. In addition, expression levels of apoptosis-, autophagy- and ER stress-related proteins were determined by western blotting. The results showed that salinomycin induced apoptosis, ER stress and autophagy in glioma cancer cell lines. In addition, salinomycin also induced ROS generation, and the ROS scavenger N-acetyl-L-cysteine was found to inhibit the salinomycin-induced apoptosis, ER stress and autophagy. The inhibition of ER stress with 4-phenylbutyric acid depressed salinomycin-induced apoptosis and autophagy. Salinomycin increased the expression of autophagy marker protein, LC3B, and accumulation of acidic vesicular organelles. Furthermore, pre-treatment with the autophagy inhibitor 3-methyladenine showed potential in increasing the apoptosis rate induced by salinomycin in the U87MG cells. Taken together, these results revealed that salinomycin induced apoptosis and autophagy via ER stress mediated by ROS, suggesting that ER stress by salinomycin plays a dual function in both promoting and suppressing cell death.

[Indexed for MEDLINE]

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