title: Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem cell.
abstract: OBJECTIVE
  Cancer stem cells (CSCs) represent a subpopulation of undifferentiated tumorigenic cells thought to be responsible for tumor initiation, maintenance, drug resistance, and metastasis. The role of CSCs in drug resistance and relapse of cancers could significantly affect outcomes of ovarian cancer patient. Therefore, therapies that target CSCs could be a promising approach for ovarian cancer treatment. The antibiotic salinomycin has recently been shown to deplete CSCs. In this study, we evaluated the effect of salinomycin on ovarian cancer stem cells (OCSCs), both alone and in combination with paclitaxel (PTX).
  
  
  METHODS
  The CD44⁺CD117⁺CSCs were obtained from the ascitic fluid of patients with epithelial ovarian cancer by using an immune magnetic-activated cell sorting system. OCSCs were treated with PTX and salinomycin either singly or in combination. Cell viability and apoptosis assays were performed and spheroid-forming ability was measured. The expression of sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 3/4 (OCT3/4) mRNA was determined using reverse transcription polymerase chain reaction, and protein expression was observed using western blot analysis.
  
  
  RESULTS
  Treatment with salinomycin alone reduced the stemness marker expression and spheroid-forming ability of OCSCs. Treatment with PTX alone did not decrease the viability of OCSCs. Treatment with a combination of salinomycin decreased the viability of OCSCs and promoted cell apoptosis. The enhancement of combination treatment was achieved through the apoptosis as determined by annexin V/propidium iodide (PI) staining, caspase-3 activity, and DNA fragmentation assay.
  
  
  CONCLUSIONS
  Based on our findings, combining salinomycin with other anti-cancer therapeutic agents holds promise as an ovarian cancer treatment approach that can target OCSCs.
authors.affiliation: Institute for Cancer Research, Keimyung University, School of Medicine, Daegu, Korea.
authors.forename: Hyun Gyo
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University, School of Medicine, Daegu, Korea.
authors.forename: So Jin
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University, School of Medicine, Daegu, Korea.
authors.forename: Hye Won
authors.identifier: http://orcid.org/0000-0001-5142-4346
authors.initials: HW
authors.lastname: Chung
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University, School of Medicine, Daegu, Korea.
authors.forename: Sang Hoon
authors.identifier: http://orcid.org/0000-0002-9121-3954
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Department of Obstetrics and Gynecology, Keimyung University, School of Medicine, Daegu, Korea.
authors.forename: Soon Do
authors.initials: SD
authors.lastname: Cha
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Jin Eui
authors.identifier: http://orcid.org/0000-0003-2072-2775
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Institute for Cancer Research, Keimyung University, School of Medicine, Daegu, Korea.|Department of Obstetrics and Gynecology, Keimyung University, School of Medicine, Daegu, Korea. chcho@kmu.ac.kr.
authors.forename: Chi Heum
authors.identifier: http://orcid.org/0000-0002-0437-4099
authors.initials: CH
authors.lastname: Cho
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use; D011714:Pyrans / Q000627:therapeutic use*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000095662:Polyether Polyketides
chemical_list: D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Apoptosis; Neoplastic Stem Cells; Salinomycin