Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/mTOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells

International Journal of Molecular Sciences
Kwang-Youn KimSoon-Cheol Ahn

Abstract

Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells. Cell viability assay, Western blot, annexin V/propidium iodide assay, acridine orange (AO) staining, caspase-3 activity assay, reactive oxygen species (ROS) production, and mitochondrial membrane potential were assayed. Our data showed that salinomycin alters the sensitivity of prostate cancer cells to autophagy. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, enhanced the salinomycin-induced apoptosis. Notably, salinomycin decreased phosphorylated of AKT and phosphorylated mammalian target of rapamycin (mTOR) in prostate cancer cells. Pretreatment with LY294002, an autophagy and PI3K inhibitor, enhanced the salinomycin-induced apoptosis by decreasing the AKT and mTOR activiti...Continue Reading

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Citations

Sep 29, 2018·Cancers·Vivek KaushikAnand K V Iyer
Feb 13, 2018·Journal of Experimental & Clinical Cancer Research : CR·Jiang JiangZeyao Tang
Jan 17, 2020·Acta Biochimica Et Biophysica Sinica·Xueming ZhangZhituo Li
Aug 20, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Peng ChenBenhong Zhou
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Oct 26, 2018·Stem Cell Research & Therapy·Qiang LiPeisheng Jin
Apr 13, 2020·Molecular Cancer·Yuan TanFaqing Tang
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Feb 13, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hsin-Yu HoMu-Kuan Chen

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Methods Mentioned

BETA
confocal microscopy
flow cytometry
electrophoresis
ELISA

Software Mentioned

Multi Gauge
Cell Quest Pro

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