ANTITUMOR ACTIVITY OF IONOPHORE ANTIBIOTIC SALINOMYCIN: THE TARGET – CANCER STEM CELLS

In this review the recent data regarding cancer stem cells (CSCs), the mechanisms of their drug resistance and the development of novel anti-CSC therapies are summarized. Recent studies suggest that salinomycin has selective toxicity for CSCs. Salinomycin is a polyether antibiotic with properties of an ionophore. This compound reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. All very recently performed studies have shown that salinomycin can function as a P-gp inhibitor to overcome drug resistance in human cancer cells. Salinomycin induced apoptosis of human prostate cancer cells owing to accumulation of reactive oxygen species, DNA damage and mitochondrial membrane depolarization. This drug also inhibits chemoresistant cancer cells and sensitizes DOX- or ETO-treated or irradiated cancer cells by increasing apoptosis causing DNA damage and reducing p21 protein level. Salinomycin inhibits Wnt signalling and selectively induces apoptosis in tumor cells. Therefore, at present salinomycin is considered to be a potential anticancer drug for cancer therapy.