| Popis: |
Ultraviolet Radiation (UVR) disruption of the immunological and physiological function of the skin has been identified as the leading cause of melanoma and non-melanoma skin cancer (NMSC). Therapeutic strategies to combat the rise in skin carcinogenesis are urgently needed. Nicotinamide (NAM), an amide form of vitamin B3, is vital to energy metabolism within cells. It is a precursor to nicotinamide adenine dinucleotide, which is essential for ATP production. By replenishing cellular energy, it helps to reverse the immune-suppressive effects of UVR on the skin and enhances repair of damaged DNA. NAM has been shown to significantly reduce the incidence of pre-malignant actinic keratoses and of NMSCs, although its effects on melanoma incidence are unknown. We investigated the effects of three concentrations of NAM (50μM, 5mM and 20mM) on the viability, proliferation and invasiveness of four melanoma human cell lines and on the viability and proliferation of two melanocyte in the presence and absence of UV radiation. We also studied tumour specimens obtained during a large double-blinded randomised placebo-controlled clinical trial of oral nicotinamide for skin cancer prevention in order to assess, via immunohistochemistry, the effects of NAM on immune cell infiltrates in and around melanomas and NMSCs. We found a significant increase in the peritumoural and tumour-infiltrating lymphocytes in melanomas arising on NAM compared to those arising on placebo. In contrast, there was no significant difference in lymphocytes in the NMSCs arising on NAM versus placebo. Rather, there was a significant decrease in the tumour infiltrating macrophages in the NAM group compared to placebo. Further, we found that 50μM NAM does not affect viability, proliferation or invasion of melanoma or melanocyte cell lines, while the higher concentrations reduced viability and proliferation. Hence NAM does not enhance the growth of melanoma cells and has inhibitory effects at high concentration. These results increase our understanding of the effects of NAM on skin carcinogenesis and its role as a chemopreventive agent, which can now be assessed in clinical trials of melanoma prevention. |
