J Gynecol Oncol.  2017 Mar;28(2):e14. 10.3802/jgo.2017.28.e14.

Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem cell

• Lee HG
• Shin SJ
• Chung HW
• Kwon SH
• Cha SD
• Lee JE
• Cho CH

• KMID: 2413456
• DOI: http://doi.org/10.3802/jgo.2017.28.e14

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.
CONCLUSION
Based on our findings, combining salinomycin with other anti-cancer therapeutic agents holds promise as an ovarian cancer treatment approach that can target OCSCs.

Keyword

Apoptosis; Salinomycin; Neoplastic Stem Cells

MeSH Terms

Anti-Bacterial Agents/*therapeutic use
Antineoplastic Agents, Phytogenic/therapeutic use
*Antineoplastic Combined Chemotherapy Protocols
*Apoptosis
Enzyme-Linked Immunosorbent Assay
Female
Humans
Neoplastic Stem Cells/*drug effects
Ovarian Neoplasms/*drug therapy/pathology
Paclitaxel/therapeutic use
Pyrans/*therapeutic use
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Anti-Bacterial Agents
Antineoplastic Agents, Phytogenic
Pyrans
Paclitaxel