Evaluation of vitamin B3, D3 and E as photoprotectors against UVB-induced damages on primary keratinocytes and fibroblasts

Non-melanoma skin cancers (NMSCs) are one of the most frequent cancers diagnosed in the elderly Caucasian population. Among several factors that contribute to NMSCs development, ultraviolet (UV) radiations are the main responsible for cancer degeneration. UV can damage cell DNA, trigger ROS production, which oxidize DNA bases causing mutations. Besides, UV inhibit immune response, activate local inflammation, trigger the production of metalloproteinases, and induce cell senescence. Most of the modifications UV-induced contribute to photocarcinogenesis and photoaging. To prevent UV-induced damages especially on high-risk patients, the use of inexpensive chemopreventive molecules with low side effects could help to prevent NMSC development. So, this thesis aims to provide new insights on the role of vitamin B3, D3, and E, in their active forms, as photoprotectors against UVB-induced damages on human primary keratinocytes and fibroblasts. We firstly demonstrated that keratinocytes isolated from field cancerization are more sensible to UV radiations in comparison with normal keratinocytes. However, nicotinamide (NAM) at 25 μM given 24h before irradiation efficiently protected keratinocytes from UVB damages reducing ROS production and DNA damages and blocking the inflammatory response. Then, we proved that NAM and vitamin D3 analog, calcipotriol, can protect human fibroblasts from photoaging by inhibiting ROS release, reducing DNA damages, restoring cell cycle, and decreasing cell senescence. Overall, our results suggest that NAM could be an efficient photoprotector against photocarcinogenesis and photoaging on both keratinocytes and fibroblasts. Moreover, vitamin D3 seems to be protect efficiently fibroblasts from premature aging. Our results might suggest that nicotinamide and vitamin D3 could be used for non-invasive treatment of field cancerization and chronically photoexposed skin areas, in order to prevent NMSC relapse and to reduce demand for surgical treatment.