Effects and Mechanism of Nicotinamide Against UVA‐ and/or UVB‐mediated DNA Damages in Normal Melanocytes

Abstract

Melanoma incidences are increasing rapidly, and ultraviolet (UV) radiation from the sun is believed to be its major contributing factor. UV exposure causes DNA damage in skin which may initiate cutaneous skin cancers including melanoma. Melanoma arises from melanocytes, the melanin-producing skin cells, following genetic dysregulations resulting into hyperproliferative phenotype and neoplastic transformation. Both UVA and UVB exposures to the skin are believed to trigger melanocytic hyperplasia and melanomagenesis. Melanocytes by themselves are deficient in repair of oxidative DNA damage and UV-induced photoproducts. Nicotinamide, an active form of vitamin B3 and a critical component of the human body's defense system has been shown to prevent certain cancers including nonmelanoma skin cancers. However, the mechanism of nicotinamide's protective effects is not well understood. Here, we investigated potential protective effects and mechanism of nicotinamide against UVA- and/or UVB- induced damage in normal human epidermal melanocytes. Our data demonstrated an appreciable protective effect of nicotinamide against UVA- and/or UVB- induced DNA damage in melanocytes by decreasing both cyclobutane pyrimidine dimers and 8-hydroxy-2'-deoxyguanosine levels. We found that the photoprotective response of nicotinamide was associated with the activation of nucleotide excision repair genes and NRF2 signaling. Further studies are needed to validate our findings in in vivo models.

Protective effects of novel derivatives of vitamin D3 and lumisterol against UVB-induced damage in human keratinocytes involve activation of Nrf2 and p53 defense mechanisms

“…The transcriptional regulation of the antioxidant defense system is promoted by the Nrf2-Antioxidant Response Element (ARE) signaling pathway which stimulates the expression of phase II detoxification enzymes including glutathione reductase (GR), heme oxygenase-1 (HO-1), catalase (CAT), manganese superoxide dismutase (MnSOD), and copper zinc superoxide dismutase (CuZnSOD) [14]. In addition, DNA damage induced by UVB irradiation is associated with Nrf2-regulated antioxidants responses in skin cells [15,16]. Thus, synthetic compounds, in particular free radical scavengers or natural products targeting Nrf2, have been proposed to be used in skin photoprotection [1,15,[17], [18], [19], [20]].…”

Protective effects of novel derivatives of vitamin D3 and lumisterol against UVB-induced damage in human keratinocytes involve activation of Nrf2 and P53 defense mechanisms

“…The transcriptional regulation of the antioxidant defense system is promoted by the Nrf2-Antioxidant Response Element (ARE) signaling pathway which stimulates the expression of phase II detoxification enzymes including glutathione reductase (GR), heme oxygenase-1 (HO-1), catalase (CAT), manganese superoxide dismutase (MnSOD), and copper zinc superoxide dismutase (CuZnSOD) [14]. In addition, DNA damage induced by UVB irradiation is associated with Nrf2-regulated antioxidants responses in skin cells [15,16]. Thus, synthetic compounds, in particular free radical scavengers or natural products targeting Nrf2, have been proposed to be used in skin photoprotection [1,15,[17][18][19][20].…”

Prevention of UV-induced skin cancer in mice by gamma oryzanol-loaded nanoethosomes

“…Nanotechnology-based cosmetics 6 , and new ingredients with anticancer 7 , antioxidant 8 , and anti-inflammatory properties 9 have been introduced into cosmetic products to prevent and/or treat skin diseases. Recently, a few studies have demonstrated the effect of specific compounds e.g., naproxen 10 , silver nanoparticles 11 , nicotinamide 12 , etc., on the prevention of UVB-induced skin cancers. The possible toxicity of chronic application of these compounds on the skin limits their routine administration as daily applied cosmeceuticals such as sunscreens.…”