Gold(i) Complex Audmap Promotes Apoptotic Responses and Inhibits Proliferation and Migration in Sk-Mel-28 Human Melanoma Cells

Metal-based chemotherapeutic agents, particularly platinum compounds, are widely used in cancer treatment; however, they are limited by systemic toxicity and drug resistance, highlighting the need for novel metallodrugs. Gold-based complexes have emerged as promising candidates due to their distinct mechanisms of action and notable antitumoral activity. Melanoma remains a highly aggressive malignancy with limited therapeutic options in advanced stages. Although several gold-based compounds have shown preclinical antitumoral potential, their effects in melanoma models remain insufficiently explored. To evaluate the in vitro antitumoral properties of the gold(I) complex (PPh3)Au(DMAP) (AuDMAP) in human melanoma cells. AuDMAP was evaluated in SK-MEL-28 melanoma cells, with non-tumoral HaCaT keratinocytes used as a comparative model. Cell viability and proliferation were assessed using MTT and SRB colorimetric assays. Cell migration was evaluated through the wound healing assay. Intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA assay and expressed as mean fluorescence intensity (MFI). Cell cycle distribution and cell death were evaluated by flow cytometry using 7-AAD and Annexin V-FITC/7-AAD staining, respectively. Transcriptional analysis was performed by quantitative PCR (qPCR). AuDMAP markedly reduced melanoma cell viability and proliferation in the low-nanomolar range, with an IC50 of ∼35.1 nM at 24h and 48h, showing greater inhibitory activity than cisplatin at concentrations = 34.4 µM (p = 0.001). In non-tumoral HaCaT keratinocytes, IC50 was ∼46,1 nM, indicating limited in vitro selectivity under the tested conditions. Based on these data, the 34.4 nM dose was selected for subsequent assays. At this concentration, AuDMAP significantly impaired melanoma cell migration, reducing wound closure percentage when compared to control, at both 24h (4.7% vs. 40.5%; p = 0.05) and 48h (1.6% vs. 74.6%; p = 0.05). In contrast, keratinocytes exhibited higher migratory activity, with increased wound closure at 24h (76.1% vs. 48.9%; p = 0.05) and 48h (85.8% vs. 48.9%; p = 0.05). Treatment with AuDMAP increased ROS levels in melanoma cells, expressed by a higher MFI at 24h (1154 vs. 637; p = 0.05) and 48h (1334 vs. 640; p = 0.05). In HaCaT keratinocytes, MFI was higher than control at 24h (1090 vs. 341; p = 0.05), but did not differ significantly at 48h (916 vs. 490; p > 0.05). No significant differences were found in melanoma cell cycle distribution. Conversely, analysis of cell death pathways revealed a predominance of early apoptotic markers in melanoma cells following AuDMAP treatment, at 24h (49.8% vs. 0.0%; p = 0.0001) and 48h (85.3% vs. 0.1%; p = 0.0001). In keratinocytes, no significant differences were observed at 24h (27.0% vs. 1.1%; p = 0.0001), whereas a significant increase in early apoptosis was detected only at 48h (41.4% vs. 0.0%; p = 0.01). Consistently, qPCR analysis revealed upregulation of JUN mRNA expression in melanoma cells (1.6 ×; p = 0.05), suggesting stress-related and pro-apoptotic transcriptional responses. AuDMAP exhibited notable antitumoral activity in SK-MEL-28 melanoma cells, combining antiproliferative and antimigratory effects with the induction of early apoptotic responses, likely associated with oxidative stress. These findings support AuDMAP as a promising metallodrug with potential therapeutic relevance for melanoma.