Effect of Melatonin and Cisplatin on Cervical Cancer Cells: Role of TRPV1 Channels

Abstract

Cisplatin, a widely used treatment for cervical cancer, and melatonin, known for enhancing the apoptotic effects of cisplatin, both play crucial roles in our study. We investigated the combined effects of these two agents on HeLa cervical cancer cells, with focus on the role of TRPV1 channels, which we found to be of significant importance. According to the treatment performed, the cell samples were divided into seven main groups: control, cisplatin,Cisplatin + capsazepine (TRPV1 antagonist), melatonin, melatonin + capsazepine, cisplatin + melatonin, and cisplatin + melatonin + capsazepine. Each group was stimulated with capsaicin (TRPV1 agonist) in all analyses. We measured apoptosis, cytosolic calcium, intracellular reactive oxygen species, mitochondrial depolarization, caspase-9, and caspase-3 levels. The combined application of cisplatin and melatonin led to a significant increase in apoptosis levels, which were statistically significantly higher compared to both the control group and the group treated with cisplatin alone (p<0.001) (Fig. 2). This notable increase underscores the potential of this combined treatment in treating cervical cancer. Our findings strongly suggest that melatonin could be a promising adjunct therapy for cisplatin-induced cervical cancer. By elevating cytosolic Ca²⁺ levels, promoting apoptosis, and increasing intracellular ROS levels through TRPV1 channels, melatonin indicated potential as an effective therapeutic option (Fig. 1–4).