Salinomycin activates AMP-activated protein kinase-dependent autophagy in cultured osteoblastoma cells: a negative regulator against cell apoptosis

PloS One
Lun-qing ZhuXiao-dong Wang

Abstract

The malignant osteoblastoma has poor prognosis, thus the search for novel and more efficient chemo-agents against this disease is urgent. Salinomycin induces broad anti-cancer effects both in vivo and in vitro, however, its role in osteoblastoma is still not clear. Salinomycin induced both apoptosis and autophagy in cultured U2OS and MG-63 osteoblastoma cells. Inhibition of autophagy by 3-methyladenine (3-MA), or by RNA interference (RNAi) of light chain 3B (LC3B), enhanced salinomycin-induced cytotoxicity and apoptosis. Salinomycin induced a profound AMP-activated protein kinase (AMPK) activation, which was required for autophagy induction. AMPK inhibition by compound C, or by AMPKα RNAi prevented salinomycin-induced autophagy activation, while facilitating cancer cell death and apoptosis. On the other hand, the AMPK agonist AICAR promoted autophagy activation in U2OS cells. Salinomycin-induced AMPK activation was dependent on reactive oxygen species (ROS) production in osteoblastoma cells. Antioxidant n-acetyl cysteine (NAC) significantly inhibited salinomycin-induced AMPK activation and autophagy induction. Salinomycin activates AMPK-dependent autophagy in osteoblastoma cells, which serves as a negative regulator against cel...Continue Reading

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Dec 3, 2014·Biochemical and Biophysical Research Communications·Zhi XieYa-fang Shen
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Methods Mentioned

BETA
ubiquitination
confocal microscopy
transfection
ELISA
co-IP
protein concentration assay
flow cytometry
fluorescence-activated cell sorting
enzyme-linked immunosorbent assay
PCR

Software Mentioned

SPSS
ImageJ

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