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

Sun Nyoung Yu, Sang Hun Kim, Kwang Youn Kim, Jae Hoon Ji, Young Kyo Seo, Hak Sun Yu, Soon Cheol Ahn

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3321-3328
Number of pages8
JournalOncology reports
Volume37
Issue number6
DOIs
StatePublished - Jun 2017
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • ER stress
  • Salinomycin
  • U87MG cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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