title: Salinomycin inhibits Akt/NF-κB and induces apoptosis in cisplatin resistant ovarian cancer cells.
abstract: BACKGROUND
  Despite advances in treatment, ovarian cancer is the most lethal gynecologic malignancy. Therefore significant efforts are being made to develop novel strategies for the treatment of ovarian cancer. Salinomycin has been shown to be highly effective in the elimination of cancer stem cells both in vitro and in vivo. The present study focused on investigating important cell signaling molecules such as Akt and NF-κB during salinomycin-induced apoptosis in cisplatin resistant ovarian cancer cells (A2780cis).
  
  
  METHODS
  MTT assay was performed to determine cell viability. Flow cytometry and DNA fragmentation assay were performed to analyze the effect on cell cycle and apoptosis. The expression of apoptosis related proteins was evaluated by Western blot analysis.
  
  
  RESULTS
  The cell viability was significantly reduced by salinomycin treatment in a dose dependent manner. The flow cytometry result showed an increase in sub-G1 phase. Salinomycin inhibited the nuclear transportation of NF-κB, and downregulated Akt expression. Declined Bcl-2, activation of caspase-3 and increased PARP cleavage triggered apoptosis. Moreover, DNA fragmentation assay also revealed apoptotic induction.
  
  
  CONCLUSIONS
  The result suggested that salinomycin-induced apoptosis in A2780cis was associated with inhibition of Akt/NF-κB. It may become a potential chemotherapeutic agent for the cisplatin resistant ovarian cancer therapy.
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: Hyun-Gyo
authors.initials: HG
authors.lastname: Lee
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kwon
authors.forename: Soon-Do
authors.initials: SD
authors.lastname: Cha
authors.forename: So-Jin
authors.initials: SJ
authors.lastname: Shin
authors.forename: Gun-Ho
authors.initials: GH
authors.lastname: Lee
authors.forename: Insoo
authors.initials: I
authors.lastname: Bae
authors.forename: Chi-Heum
authors.initials: CH
authors.lastname: Cho
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D011714:Pyrans / Q000008:administration & dosage / Q000494:pharmacology*; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides