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.