Abstract

Acute myeloid leukemia (AML) remains a significant therapeutic challenge, necessitating the exploration of novel strategies to enhance the efficacy of standard chemotherapeutic agents like Cytarabine (Ara-C). This study investigated the potential of melatonin, a pleiotropic indoleamine, to augment the anti-leukemic effects of Ara-C in the human promyelocytic leukemia cell line, HL-60. Our primary objective was to determine the synergistic cytotoxic effects and elucidate the underlying cellular and molecular mechanisms, particularly those related to cell cycle progression and apoptosis. HL-60 cells were treated with Ara-C and melatonin, both individually and in combination. The results demonstrate that co-administration significantly reduced cell viability and proliferation compared to single-agent treatments. Mechanistically, the combination therapy was found to induce a more pronounced G0/G1 cell cycle arrest and dramatically increase the rate of apoptosis, evidenced by enhanced caspase-3 activity and altered expression of key regulatory proteins. These findings suggest that melatonin acts as a potent chemosensitizer, likely by modulating membrane-associated signaling pathways or intracellular redox status, thereby lowering the apoptotic threshold. This synergistic approach offers a promising therapeutic avenue for improving AML treatment outcomes and warrants further in vivo investigation.