Using zebrafish melanoma xenografts and bioinformatics, the authors evaluated Parkinson's drugs amantadine, rasagiline, and carbidopa, reporting LC50 values, limited anti‑melanoma efficacy (only dose‑dependent effects for amantadine), and molecular associations between PD and melanoma.

While it offers limited direct insight into PD neuroprotective mechanisms, the paper provides in vivo safety/toxicity data, a zebrafish platform for repurposing screens, and bioinformatic links that could inform comorbidity studies or hypotheses for future repurposing efforts.

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 (LC50) of the drugs tested. Rasagiline exhibited an LC50 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 effects on melanoma cells in a living organism.