Anti-Cancer Effects of Cyanidine-3 Cisplatin, and Dacarbazine Combination in the A375 Melanoma Cell

Abstract

Malignant melanoma (MM) represents the most lethal form of cutaneous neoplasm. Cyanidin 3-O-glucoside (Cy3G) exhibits anticarcinogenic and antioxidant properties. The aim of this study was to investigate the effects of Cy3G in combination with cisplatin (DDP) and dacarbazine (DTIC) on A375 melanoma cells. The cytotoxic effects of Cy3G, DDP, and DTIC were evaluated by XTT assay. The expression of genes associated with the cell cycle, apoptosis, and six miRNAs were analyzed by RT-PCR. Apoptotic changes were assessed using the TUNEL assay. Cell invasion and migration were evaluated by Matrigel-chamber and wound-healing assays. Oxidative stress index (OSI) was also calculated. The IC50 dose of Cy3G was determined as 592.77 mu M at 48 h. In the Cy3G + DDP + DTIC group, caspase-10 expression increased, while CDK4, caspase-8, Bax, Bcl-2, and TIMP2 expression levels decreased. A significant reduction in miRNA-211, miRNA-10b, miRNA-18a-5p, and miRNA-7-5p was also observed in this group. All combination groups showed a marked decrease in invasion and migration. Notably, the Cy3G + DDP + DTIC combination significantly increased the number of apoptotic cells. Although Cy3G alone showed minimal effects in OSI, its combination with DDP and DTIC enhanced oxidative stress responses. Overall, Cy3G appeared to potentiate the antiproliferative and antimetastatic effects of DDP and DTIC, suggesting its potential as a supportive agent in melanoma treatment.