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Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem cell
Hyun Gyo Lee1, So Jin Shin2, Hye Won Chung2
1Institute for Cancer Research, Keimyung University, School of Medicine, Daegu, Korea.
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.
Insights
Salinomycin effectively targets ovarian cancer stem cells (OCSCs), reducing their stemness. Combining salinomycin with paclitaxel enhances OCSC apoptosis and viability reduction, offering a promising ovarian cancer treatment strategy.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
- Pharmacology
Background:
- Cancer stem cells (CSCs) drive tumor initiation, metastasis, and drug resistance.
- Targeting CSCs is crucial for effective ovarian cancer treatment.
- Salinomycin has shown potential in depleting CSCs.
Purpose of the Study:
- To evaluate the efficacy of salinomycin on ovarian cancer stem cells (OCSCs).
- To assess the combined effect of salinomycin and paclitaxel (PTX) on OCSCs.
- To investigate the impact on OCSC viability, apoptosis, and stemness markers.
Main Methods:
- OCSCs were isolated from epithelial ovarian cancer patients using immune magnetic-activated cell sorting.
- Cells were treated with salinomycin and PTX, alone and in combination.
- Assays included cell viability, apoptosis, spheroid formation, and analysis of stemness markers (SOX2, OCT3/4) via RT-PCR and Western blot.
Main Results:
- Salinomycin alone reduced OCSC stemness markers and spheroid formation.
- PTX alone did not significantly decrease OCSC viability.
- Combination therapy markedly decreased OCSC viability and induced apoptosis, confirmed by Annexin V/PI staining, caspase-3 activity, and DNA fragmentation.
Conclusions:
- Salinomycin demonstrates activity against OCSCs.
- Combining salinomycin with PTX enhances anti-cancer effects by promoting apoptosis.
- This combination therapy presents a promising strategy for targeting OCSCs in ovarian cancer treatment.
