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.

PubMed

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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