Epidemiological and clinical studies show a clear association between melanoma, a highly aggressive form of skin cancer, and a neurodegenerative disorder—Parkinson’s disease (PD). Patients with PD have a higher risk of developing melanoma and vice versa, although the precise mechanisms underlying this relationship remain poorly understood. Drugs commonly used in Parkinson’s disease treatment, including amantadine, rasagiline and carbidopa (C-DOPA), have gained attention for their potential anticancer properties. However, the evidence supporting this requires further research. Here, we used a zebrafish ( Danio rerio ) as a model system, due to its rapid development and transparency, to study the effect of the aforementioned drugs in vivo. We determined the lethal concentration (LC 50 ) of the drugs tested. Rasagiline exhibited an LC 50 three times higher than that of amantadine and C-DOPA. We also established a zebrafish embryonic human melanoma xenograft model using the SK-MEL-28, FM-55-P, and FM-55-M2 melanoma cell lines. The impact on melanoma cells in a zebrafish xenograft model was comparable to the control for rasagiline and C-DOPA, suggesting limited efficacy against melanoma in this context. Amantadine demonstrated modest dose-dependent effects with a significant decrease in proliferation at higher doses. While these drugs were not expected to have strong anticancer effects, the findings support their safety profile in this context. Our bioinformatics analysis showed molecular associations between the two diseases but also studied drug targets. Further development and investigation are needed to explore the potential effects of PD drugs on human melanoma and to better understand the complex association between both diseases. The use of zebrafish as a xenotransplantation model offers great opportunities to investigate such drugs and their long-term effects on melanoma cells in a living organism. • The zebrafish xenograft model offers an ethical, real-time platform for studying melanoma–Parkinson’s disease drug interactions in vivo. • Amantadine exhibits a dose-dependent decrease in melanoma proliferation, indicating potential for drug repurposing. • Integrated bioinformatic analyses identify common molecular pathways and drug targets shared between melanoma and Parkinson’s disease. • The study emphasizes the translational importance of using neurodegenerative disease drugs in cancer research, supported by strong in silico and in vivo evidence.
Krasowska et al. (Wed,) studied this question.
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