title: Salinomycin activates AMP-activated protein kinase-dependent autophagy in cultured osteoblastoma cells: a negative regulator against cell apoptosis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Salinomycin activates AMPK-dependent autophagy in osteoblastoma cells, which serves as a negative regulator against cell apoptosis. AMPK-autophagy inhibition might be a novel strategy to sensitize salinomycin's effect in cancer cells.
authors.affiliation: The Center of Diagnosis and Treatment for Children's Bone Diseases, the Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.
authors.forename: Lun-qing
authors.initials: LQ
authors.lastname: Zhu
authors.affiliation: The Center of Diagnosis and Treatment for Children's Bone Diseases, the Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.
authors.forename: Yun-fang
authors.initials: YF
authors.lastname: Zhen
authors.affiliation: The Center of Diagnosis and Treatment for Children's Bone Diseases, the Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Center of Diagnosis and Treatment for Children's Bone Diseases, the Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.
authors.forename: Zhi-xiong
authors.initials: ZX
authors.lastname: Guo
authors.affiliation: The Center of Diagnosis and Treatment for Children's Bone Diseases, the Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.affiliation: The Center of Diagnosis and Treatment for Children's Bone Diseases, the Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D018215:Osteoblastoma / Q000378:metabolism*; D011714:Pyrans / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000095662:Polyether Polyketides
chemical_list: D055372:AMP-Activated Protein Kinases; D011714:Pyrans; D017382:Reactive Oxygen Species; C010327:salinomycin; D000095662:Polyether Polyketides