Polyether
ionophore salinomycin (SAL) and its semi-synthetic derivatives are recognized as very promising anticancer drug candidates due to their activity against various types of
cancer cells, including multidrug-resistant populations.
Ovarian cancer is the deadliest among gynecologic
malignancies, which is connected with the development of chemoresistant forms of the disease in over 70% of patients after initial treatment regimen. Thus, we decided to examine the anticancer properties of SAL and selected SAL derivatives against a series of drug-sensitive (A2780, SK-OV-3) and derived drug-resistant (A2780 CDDP, SK-OV-3 CDDP)
ovarian cancer cell lines. Although SAL analogs showed less promising IC50 values than SAL, they were identified as the
antitumor agents that significantly overcome the resistance to
platinum-based drugs in
ovarian cancer, more potent than unmodified SAL and commonly used anticancer drugs-5-fluorouracil,
gemcitabine, and
cisplatin. Moreover, when compared with SAL used alone, our experiments proved for the first time increased selectivity of SAL-based dual
therapy with
5-fluorouracil or
gemcitabine, especially towards A2780 cell line. Looking closer at the results, SAL acted synergistically with
5-fluorouracil towards the drug-resistant A2780 cell line. Our results suggest that combinations of SAL with other
antineoplastics may become a new therapeutic option for patients with
ovarian cancer.