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Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress
K Ketola1, M Hilvo, T Hyötyläinen
1Medical Biotechnology, VTT Technical Research Centre of Finland, University of Turku, PL 106, FI-20521 Turku, Finland.
Background:
We have shown that a sodium ionophore monensin inhibits prostate cancer cell growth. A structurally related compound to monensin, salinomycin, was recently identified as a putative cancer stem cell inhibitor.
Methods:
The growth inhibitory potential of salinomycin was studied in a panel of prostate cells. To get insights into the mechanism of action, a variety of assays such as gene expression and steroid profiling were performed in salinomycin-exposed prostate cancer cells.
Results:
Salinomycin inhibited the growth of prostate cancer cells, but did not affect non-malignant prostate epithelial cells. Salinomycin impacted on prostate cancer stem cell functions as evidenced by reduced aldehyde dehydrogenase activity and the fraction of CD44(+) cells. Moreover, salinomycin reduced the expression of MYC, AR and ERG, induced oxidative stress as well as inhibited nuclear factor-κB activity and cell migration. Furthermore, profiling steroid metabolites revealed increased levels of oxidative stress-inducing steroids 7-ketocholesterol and aldosterone and decreased levels of antioxidative steroids progesterone and pregnenolone in salinomycin-exposed prostate cancer cells.
Conclusion:
Our results indicate that salinomycin inhibits prostate cancer cell growth and migration by reducing the expression of key prostate cancer oncogenes, inducing oxidative stress, decreasing the antioxidative capacity and cancer stem cell fraction.
Insights
Salinomycin effectively inhibits prostate cancer cell growth and stem cell functions. This compound reduces oncogene expression and migration while inducing oxidative stress, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Monensin, a sodium ionophore, inhibits prostate cancer cell growth.
- Salinomycin, a related compound, is a potential cancer stem cell inhibitor.
Purpose of the Study:
- To investigate the growth inhibitory effects of salinomycin on prostate cancer cells.
- To elucidate the mechanism of action of salinomycin in prostate cancer.
Main Methods:
- Assessed salinomycin's effect on prostate cancer cell growth and stem cell markers (aldehyde dehydrogenase activity, CD44 expression).
- Analyzed gene expression (MYC, AR, ERG), oxidative stress markers, nuclear factor-κB activity, and cell migration.
- Performed steroid metabolite profiling to assess changes in oxidative and antioxidative steroids.
Main Results:
- Salinomycin inhibited prostate cancer cell growth but not non-malignant cells.
- Reduced cancer stem cell fraction, MYC, AR, ERG expression, and nuclear factor-κB activity.
- Induced oxidative stress and inhibited cell migration; altered steroid metabolism towards increased oxidative and decreased antioxidative profiles.
Conclusions:
- Salinomycin demonstrates potent anti-cancer properties against prostate cancer.
- Mechanism involves downregulating oncogenes, reducing stemness, inducing oxidative stress, and inhibiting migration.
- Salinomycin represents a promising therapeutic agent for prostate cancer treatment.
