title: Salinomycin induces apoptosis via death receptor-5 up-regulation in cisplatin-resistant ovarian cancer cells.
abstract: BACKGROUND
  Chemo-resistance to cisplatin-centered cancer therapy is a major obstacle to effective disease treatment. Recently, salinomycin was proven to be highly-effective for the elimination of cancer stem cells both in vitro and in vivo. The objective of the present study was to evaluate the anticancer properties of salinomycin in cisplatin-resistant ovarian cancer cells (A2780cis).
  
  
  METHODS
  The tetrazolium dye (MTT) assay was used to determine cell viability. Flow cytometric analysis was performed to analyze the effect on cell cycle and apoptosis. The expression of apoptosis-related proteins was evaluated by western blot analysis.
  
  
  RESULTS
  Cell viability was significantly reduced by salinomycin treatment in a dose-dependent manner. Flow cytometry showed an increase in sub-G1 phase cells. Salinomycin increased the expression of death receptor-5 (DR5), caspase-8 and Fas-associated protein with death domain (FADD). A decline in the expression of FLICE-like inhibitory protein (FLIP), activation of caspase-3 and increased poly ADP-ribose polymerase (PARP) cleavage, triggered apoptosis. Furthermore, annexin-V staining also revealed the apoptotic induction.
  
  
  CONCLUSIONS
  These findings provide important insights regarding the activation of caspase-8 and DR5, to our knowledge, for the first time in salinomycin-treated cisplatin-resistant ovarian cancer and demonstrate that salinomycin could be a prominent anticancer agent.
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Bidur
authors.initials: B
authors.lastname: Parajuli
authors.forename: So-Jin
authors.initials: SJ
authors.lastname: Shin
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kwon
authors.forename: Soon-Do
authors.initials: SD
authors.lastname: Cha
authors.forename: Rosa
authors.initials: R
authors.lastname: Chung
authors.forename: Won-Jin
authors.initials: WJ
authors.lastname: Park
authors.forename: Hyun-Gyo
authors.initials: HG
authors.lastname: Lee
authors.forename: Chi-Heum
authors.initials: CH
authors.lastname: Cho
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011714:Pyrans / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000095662:Polyether Polyketides
chemical_list: D017304:Annexin A5; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D020169:Caspases; D002945:Cisplatin; D011714:Pyrans; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C010327:salinomycin; D000095662:Polyether Polyketides