Oral and Poster Presentation 18th International Congress on Photobiology 2024

Efficacy of oral nicotinamide monotherapy versus combinational treatments in the prevention of ultraviolet radiation-induced skin cancer (#153)

Celina Pihl 1 , Peter Bjerring 2 , Flemming Andersen 2 3 , Merete Haedersdal 1 , Catharina M. Lerche 1 4
  1. Department of Dermatology , Copenhagen University Hospital - Bispebjerg Hospital, Copenhagen, Denmark
  2. Department of Dermatology , Aalborg University Hospital, Aalborg, Denmark
  3. Department of Dermatology , Private Hospital Molhom, Vejle, Denmark
  4. Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark

Keratinocyte carcinomas (KC) are cancers of the skin predominantly caused by ultraviolet radiation (UVR). Oral nicotinamide (Vitamin B3; NAM) is reported to reduce KC and pre-malignant lesions in healthy volunteers. Here, we report the efficacy of three monotherapies (NAM, phloroglucinol [PG], and metformin [Met]) and two combinational treatments (NAM-PG and NAM-Met) in preventing UVR-induced skin cancer. Female hairless C3.Cg-Hrhr/TifBom Tac mice were exposed to UVR of 3.5 standard erythema doses three times a week to induce skin cancer development. In three subsequent experiments, mice (n = 25 per group) were treated concurrently to UVR with i) 600 mg/kg NAM or 100 mg/kg PG, ii) 600 mg/kg NAM or 300 mg/kg Met, iii) 600 mg/kg NAM, 75 mg/kg PG + 400 mg/kg NAM, or 200 mg/kg Met + 400 mg/kg NAM. In all three experiments, a UVR control group was also included. Our data showed significant protection provided by PG and NAM monotherapies compared to the UVR control group (p ≤ 0.036). Met monotherapy did not reduce tumour development (p > 0.05). In the combination study, all three treatments protected against tumour development (p ≤ 0.015). NAM-Met was less effective compared to NAM-monotherapy (p ≤ 0.01), indicating inferior photoprotection. In contrast, NAM-PG reduced pyrimidine-pyrimidone (6-4) photoproducts measured by immunohistochemistry in comparison to both the UVR control group (40%; p ≤ 0.0021) and NAM-monotherapy (37%; p ≤ 0.0082). Our data indicate that the combination of two treatments (NAM and PG) provides effective pre-clinical photoprotection even at a reduced dose. The reduction in DNA damage could suggest that NAM and PG may synergise to mediate an improved protective mechanism better suited for keratinocyte carcinoma prevention.