In this study, we investigated the effects of blue light and 5-aminolevulinic acid (5-ALA) co-treatment on B16F1 melanoma cells and HaCaT keratinocytes. We focused on cellular responses, including mitochondrial function, DNA integrity, and gene expression. Co-treatment significantly damaged the mitochondria, altered their morphology, induced mitochondrial membrane depolarization, increased intracellular reactive oxygen species, and led to cardiolipin peroxidation in both cell types. This approach promoted DNA fragmentation and apoptosis. However, blue light and co-treatment with 5-ALA did not enhance the formation of cyclobutane pyrimidine dimers, 6-4 photoproducts, or Dewar photoproducts. Moreover, it triggered complex, time-dependent changes in gene expression, particularly the upregulation of MMP-1 and p21 in HaCaT cells. Our findings revealed that blue light and 5-ALA co-treatment caused substantial cellular stress and damage, suggesting their therapeutic potential against melanoma and highlighting the need for caution and precision in their application to avoid harming normal cells. This underscores the necessity for further research to refine therapeutic approaches.
