GOLD(I)-BASED COMPLEX AUDMAP: A PROMISING ANTIPROLIFERATIVE AGENT FOR MELANOMA TREATMENT

Introduction/Justification

Melanoma is the most aggressive type of skin cancer, with increasing global incidence. Platinum-based chemotherapy, particularly cisplatin, remains a standard treatment, but its effectiveness is often limited by drug resistance and severe side effects. Gold-based complexes have gained attention as potential alternatives due to their greater chemical stability, selective cytotoxicity against platinum-resistant cells, lower systemic toxicity, and immunomodulatory effects. Previous studies from our group demonstrated the antiproliferative activity of AuDMAP, a gold(I)-based complex, in the UACC-62 melanoma cell line. Building on these findings, this study investigates the antiproliferative effects, cytotoxicity, and selectivity of AuDMAP in SK-MEL-28 and A-375 melanoma cells, as well as its impact on cell migration and potential anti-metastatic properties in comparison to cisplatin.

Objectives

To evaluate the antiproliferative activity and cell death mechanisms induced by the AuDMAP complex in SK-MEL-28 and A-375 melanoma cell lines, as well as determining its toxicity against non-tumoral HaCaT cells.

Materials and Methods

Melanoma and non-tumor cells were cultured in DMEM + 10% FBS + 1% penicillin-streptomycin and treated with AuDMAP (0.78–100 µM) for 48h, with cisplatin as a control. Sulforhodamine B (SRB) and Thiazolyl Blue Tetrazolium Bromide (MTT) assays were performed to determine cell viability, antiproliferative activity, and IC50 values. The wound healing assay assessed migration, and flow cytometry will be conducted to explore cell death mechanisms and cell cycle effects.

Results

AuDMAP exhibited strong antiproliferative activity, inhibiting ∼80% of cell proliferation at 6.25 µM in melanoma cells - 15x more effective than cisplatin for SK-MEL-28 and 3.3x for A-375. IC50 values were 2.61 µM (SK-MEL-28), 2.50 µM (A-375), and 1.81 µM (HaCaT), yielding a low Selectivity Index (0.69–0.72). Migration assays revealed that AuDMAP significantly reduced wound closure, suggesting anti-metastatic potential. In A-375, wound closure was -8.5% with AuDMAP vs. 62.8% with cisplatin (6.25 µM), while in SK-MEL-28, closure was 4.6% vs. -13.5%, respectively. Given these promising results, further studies will focus on cell cycle analysis and death mechanisms to better understand the biological effects of AuDMAP.

Conclusion

AuDMAP is a gold(I)-based complex that demonstrates potent antiproliferative and anti-migratory effects in melanoma cells, with efficacy significantly superior to cisplatin in the tested models. The inhibition of cell proliferation and migration suggests its potential as a promising anticancer agent, possibly disrupting tumor progression and metastasis. However, the low selectivity index observed indicates that its cytotoxic effects extend to non-tumor cells, raising concerns about the safety profile in intravenous administration. To further explore its therapeutic viability, future studies will investigate its mechanisms of action at the molecular level, focusing on cell cycle modulation and programmed cell death pathways. These findings contribute to the growing interest in gold(I) compounds as novel candidates for melanoma treatment, particularly for topical administration.

Acknowledgements

This study was supported by grants from the Brazilian Agencies FAPESP (2021/10265-8 Cancer Theranostics Innovation Center - CEPID), and Program (PPPD) at the University of Campinas (UNICAMP, ID Number 325141).