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Nicotinamide Promotes Apoptosis in Malignant Melanoma via PARP1 Inhibition and Mitochondrial Pathway Activation
Yao Yu1, Zhizhan Ni2, Bujun Ge2
1Department of Dermatology, Shanghai Putuo District Liqun Hospital, Shanghai, China.
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.
Insights
Nicotinamide induces apoptosis in melanoma cells by inhibiting Poly (ADP-ribose) polymerase 1 (PARP1). This targeted approach may offer a new strategy for treating malignant melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Nicotinamide (NAM) shows potential in inducing apoptosis in malignant melanoma cells.
- The precise molecular mechanisms underlying NAM's anti-melanoma effects are not fully understood.
Purpose of the Study:
- To predict and analyze the apoptotic targets of NAM in malignant melanoma using network pharmacology and bioinformatics.
- To experimentally validate the role of NAM in inhibiting Poly (ADP-ribose) polymerase 1 (PARP1) and inducing mitochondrial apoptosis.
Main Methods:
- Network pharmacology and bioinformatics analyses were employed to identify potential targets.
- Experimental validation involved using mouse melanoma cells (B16) to assess apoptosis, PARP1 function, mitochondrial potential, and protein expression.
- Gene Set Enrichment Analysis (GSEA) and GEPIA2 database were utilized for pathway and expression analysis.
Main Results:
- PARP1 was identified as a key apoptotic target of NAM in malignant melanoma.
- High PARP1 expression correlated with poor prognosis and predicted 1-year survival in melanoma patients.
- NAM treatment in B16 cells increased apoptosis, decreased PAR expression, reduced mitochondrial membrane potential, and upregulated mitochondrial apoptotic proteins.
Conclusions:
- NAM promotes apoptosis in mouse melanoma cells, likely via PARP1 inhibition.
- This mechanism involves the mediation of the mitochondrial apoptotic pathway in malignant melanoma.
- PARP1 is a potential therapeutic target and prognostic biomarker in melanoma and other cancers.
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