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. 2024 Nov 27;14(12):1512.
doi: 10.3390/biom14121512.

Role of Nicotinamide in the Pathogenesis of Actinic Keratosis: Implications for NAD+/SIRT1 Pathway

Riccardo Belardi  1 , Francesca Pacifici  1   2   3 , Terenzio Cosio  4   5 , Sara Lambiase  4 , Ruslana Gaeta Shumak  4 , Fabio Artosi  4 , Antonia Rivieccio  4 , Danilo Cavalloro  4 , Elena Dellambra  6 , Luca Bianchi  4 , David Della-Morte  2   3   7   8 , Elena Campione  4
Affiliations

Role of Nicotinamide in the Pathogenesis of Actinic Keratosis: Implications for NAD+/SIRT1 Pathway

Riccardo Belardi et al. Biomolecules. .

Abstract

Actinic keratosis (AK) is a precursor to invasive squamous cell carcinoma, making early diagnosis and treatment essential to prevent progression. Among available therapeutic options, nicotinamide (NAM) has shown potential in reducing AK progression. NAM is a precursor of nicotinamide adenine dinucleotide (NAD+), which activates sirtuin (SIRT)1, a protein with anti-cancer properties. Although the role of SIRT1 in AK is still debated, no data currently exist on the systemic modulation of this protein in AK. Therefore, this study aims to evaluate whether NAM, by increasing serum NAD+ levels, may promote SIRT1 activation in peripheral blood mononuclear cells (PBMCs) in AK patients. Thirty patients were enrolled and treated with NAM for 24 months. Hematological, biochemical, and skin condition assessments were conducted, alongside the measurement of SIRT1 and NAD+ levels. A decrease in basophils, monocytes, total cholesterol, and blood glucose levels was observed in the study group, along with a reduction in AK lesions. Notably, NAM treatment significantly enhanced serum NAD+ levels, and nuclear SIRT1 activity in PBMCs. In conclusion, NAM administration significantly reduced AK progression in a NAD+/SIRT1-dependent manner, supporting its role as a chemopreventive agent in AK management.

Keywords: NAD+; actinic keratosis; sirtuin 1 activity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Evaluation of Actinic Keratosis (AK) lesion number in patients at T0 and T24, along with a representative patient’s image (** p < 0.005).
Figure 2
Figure 2
Sera levels of Nicotinamide Adenine Dinucleotide (NAD): (a) sera levels of Total NAD (NADt) in patients at T0 and T24; (b) sera levels of NAD + Hydrogen (NADH) in patients at T0 and T24; (c) sera levels of NAD Plus (NAD+) in patients at T0 and T24. ** p < 0.01; *** p < 0.001. pmol, picomoles.
Figure 3
Figure 3
(a) Sera levels of NAD+-dependent deacetylases of the Sirtuin 1 (SIRT1) in patients at T0 and T24. (b) Nuclear activity of SIRT1 in peripheral blood mononuclear cells (PBMCs:) comparison of nuclear activity, monitored over 1 h, of Sirtuin1 (SIRT1), extracted from PBMCs, in patients at T0 and T24. (**** p < 0.0001). FI: fluorescence intensity.
See this image and copyright information in PMC

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