Melatonin promotes cytotoxicity while reducing cell motility and antioxidant defenses in ovarian cancer cell lines

Ovarian cancer (OC), a highly recurrent and fatal tumor, poses diagnostic challenges due to generic symptoms and chemoresistance. Melatonin (Mel) is an indoleamine acting against tumor progression and exhibiting pro-oxidative actions in tumor cells. This in vitro study explores the impact of Mel on antioxidant defenses of OC cells (high-grade SKOV-3 and low-grade CAISMOV-24 lines), focusing on its receptor-dependent and -independent effects. Cell viability was evaluated through MTT assay and antioxidant system was assessed in supernatants by measuring glutathione (GS), reduced (GSH) and oxidized (GSSG) glutathione, catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD). Mel accumulated intracellularly and exerted cytotoxic effects, reducing cell viability in both cell lines. Notably, Mel independently of its membrane receptors, inhibited migration and invasion, thus showing its anti-tumoral potential. By investigating melatonin's actions, we observed an impact on the antioxidant system primarily through the reduced activity of CAT and the GS axis. The modulation of these antioxidants by Mel demonstrates its multifaceted role in OC, emphasizing its therapeutic potential. We also demonstrated, for the first time, the theoretical ability of Mel to bind to CAT, which may be responsible for the reduction in enzyme activity. This study provides novel insights into Mel's receptor-independent actions and supports its potential as an adjuvant therapeutic agent in OC.