Belardi Riccardo, Pacifici Francesca, Cosio Terenzio, Lambiase Sara, Shumak Ruslana Gaeta, Artosi Fabio, Rivieccio Antonia, Cavalloro Danilo, Dellambra Elena, Bianchi Luca, Della-Morte David, Campione Elena
Clinical Laboratory Medicine Unit, Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy.
Biomolecules. 2024 Nov 27;14(12):1512. doi: 10.3390/biom14121512.
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.
光化性角化病（AK）是浸润性鳞状细胞癌的前驱病变，因此早期诊断和治疗对于预防病情进展至关重要。在现有的治疗选择中，烟酰胺（NAM）已显示出降低AK进展的潜力。NAM是烟酰胺腺嘌呤二核苷酸（NAD）的前体，可激活具有抗癌特性的蛋白质sirtuin（SIRT）1。尽管SIRT1在AK中的作用仍存在争议，但目前尚无关于该蛋白在AK中全身调节的数据。因此，本研究旨在评估NAM是否通过提高血清NAD +水平，促进AK患者外周血单核细胞（PBMC）中SIRT1的激活。30名患者入组并接受NAM治疗24个月。进行了血液学、生化和皮肤状况评估，同时测量了SIRT1和NAD水平。研究组观察到嗜碱性粒细胞、单核细胞、总胆固醇和血糖水平降低，同时AK病变减少。值得注意的是，NAM治疗显著提高了血清NAD水平和PBMC中的核SIRT1活性。总之，NAM给药以NAD / SIRT1依赖性方式显著降低了AK进展，支持其作为AK管理中化学预防剂的作用。
