Exploring Phytochemical Adjuvant Therapy in Melanoma Treatment: The Effects of MAZ-51 and Zingerone on Melanoma Cell Proliferation

Abstract

Current melanoma treatment results in adverse effects, prompting the use of phytochemicals as adjuvant therapy to reduce the reliance on synthetic drugs and combat drug resistance. This study investigated the in vitro effect of (3-(4-Dimethylamino-naphthelen-1-ylmethylene)-1, 3-hydroindol-2-one) (MAZ-51) and zingerone, a ginger derivative, on melanoma cell proliferation in B16-F10 melanoma and HaCaT human keratinocyte cell lines. The cells were treated with MAZ-51 (0.002–0.005 mg/mL) and zingerone (0.5–2 mg/mL) at 24, 48 and 72 h, as well as combined treatment (at IC₅₀ at 48 and 72 h), to determine cell numbers using a crystal violet assay, which was also utilised to investigate the effects of vascular endothelial growth factor (VEGF) co-treated medium on cell numbers. Morphological changes were examined using haematoxylin and eosin (H&E) staining and polarisation optical density inferential contrast (PlasDIC) and cell cycle progression using flow cytometry. The B16-F10 half maximal inhibitory concentrations (IC₅₀) were 0.05428, 0.03162 and 0.01204 mg/mL for MAZ-51 at 24, 48 and 72 h, respectively, and 27.9, 2.199 and 1.219 mg/mL for zingerone at 24, 48 and 72 h respectively. Both compounds reduced cell numbers at 48 and 72 h (p < 0.05) and co-treatment with VEGF exhibited a decrease in cell numbers. Morphological analysis revealed characteristics of cell death, and flow cytometry analysis exhibited a mitotic block. Our findings demonstrate that individual treatment exhibited significant antiproliferative effects on melanoma cells. However, the combination treatment resulted in a combination index (CI) that is greater than one at IC₅₀ and IC₂₅, indicating antagonism. Therefore, future studies should consider the individual effects of the compounds on melanoma proliferation.