Efeito antitumoral da moxidectina e seu potencial sinérgico à quimioterapia com cisplatina

Abstract

The repositioning of drugs as a therapeutic alternative for cancer has gained prominence through the use of medicines approved in preclinical and clinical trials, reducing expenses and the development time of new pharmaceuticals. In this context, Moxidectin (MOX) is a broad-spectrum anthelmintic belonging to the macrocyclic lactone family. Unlike other drugs in the same family, there is a lack of studies exploring its therapeutic potential. Therefore, the aim of this study was to evaluate the antitumor potential of MOX on cervical cancer cell lines (HeLa and SiHa) and breast cancer cell lines (MCF-7 and MDA-MB-231). Cell viability was assessed after 24 and 48 hours of MOX treatment (0.48 to 62 μM) using the MTT reduction assay to determine the IC50 and selectivity index. Proliferative capacity was evaluated in the colony formation assay, as well as the morphology of treated cells. To assess the possible mechanism of action, cell death processes (apoptosis and necrosis) and cell cycle were examined, including the effect of MOX in combination with cisplatin. Results demonstrate that MOX selectively reduced cell viability in all evaluated cell lines, except for HeLa. MDA-MB-231 and SiHa cell lines were more sensitive to treatment, with IC50 values ranging from 1.055 to 4.030 μM, suggesting time-dependent toxicity. Additionally, MOX significantly reduced the ability to form new colonies in all treated cells. Data showed that MOX induced apoptosis in tumor cells with a synergistic effect with cisplatin, increasing cell death by over 80%. Combined treatment in the MCF-7 cell line resulted in an additive effect on apoptosis induction and cell cycle arrest in the S phase (49.2% of cells), suggesting cell cycle arrest as the pro-apoptotic pathway. These findings were supported by morphological changes observed in treated cells, including condensed nuclei, loss of cytoplasmic volume, and loss of cell adhesion. Conversely, in other cell lines, MOX did not induce significant changes in the cell cycle. Overall, the data highlight the antitumor activity of MOX, contributing to its repositioning in therapeutic regimens as a pharmacological adjuvant in antitumor chemotherapy.