Nicotinamide Promotes Apoptosis in Malignant Melanoma via PARP1 Inhibition and Mitochondrial Pathway Activation

ABSTRACT Nicotinamide has been reported to promote apoptosis in malignant melanoma cells, however, its mechanism remains unclear. This study aims to predict and analyze the apoptotic targets of nicotinamide in malignant melanoma through network pharmacology and bioinformatics. Experimental validation was conducted to determine whether nicotinamide inhibits PARP1 function and promotes mitochondrial apoptosis in mouse melanoma cells. PARP1 was identified as a key apoptotic target of nicotinamide in malignant melanoma. High PARP1 expression correlated with poor prognosis and was predictive of 1‐year survival in melanoma patients. PARP1 was highly expressed in all melanoma subtypes but was not associated with tumor stage or TMB. GSEA revealed three pathways active under low PARP1 expression. Nicotinamide treatment increased apoptosis in B16 melanoma cells, decreased PAR expression, reduced mitochondrial membrane potential, and upregulated mitochondrial apoptotic proteins. GEPIA2 analysis showed that PARP1 is also highly expressed in various other tumors. Nicotinamide promotes apoptosis in mouse melanoma B16 cells, potentially through PARP1 inhibition, thereby mediating the mitochondrial apoptotic pathway in malignant melanoma. Clinical Trial Number: Not applicable.