ANTICANCER ACTIVITY OF MELATONIN AND METFORMIN ALONE AND IN COMBINATION AGAINST MELANOMA AND BREAST CANCER CELLS

Drug repositioning has received increasing attention in cancer treatment. Metformin and melatonin are among the drugs screened for new biological activities that could be used in therapeutic applications. The aim of this study was to perform a predictive in silico study of the potential outcomes of melatonin and metformin co-treatment, and to evaluate the impact of melatonin and metformin individually and in combination on the growth of melanoma and breast cancer cells. Computer-based analysis identified diseases, proteins, and pathways that were susceptible to modulation by these two drugs simultaneously. Among proteins with the highest probability of interaction with both drugs were molecules related to intracellular signaling pathways and apoptosis, such as AKT kinase, MAPK8 kinase, mTOR, FOXO3, p53, and caspases. These results revealed that the simultaneous use of melatonin and metformin exerted an additive or synergistic inhibitory effect on the growth of breast cancer cells, although this effect was not observed in melanoma cells. The synergistic effect of both compounds used together was caused by the reduced proliferation and/or increased apoptosis of breast cancer cells. In conclusion, our results indicate that the combination of melatonin and metformin may have potential anticancer effects on breast cancer cells. However, additional studies are needed to evaluate the mechanism of action of the combined treatment of melatonin and metformin in cancer cells.