Aspirin Protects Melanocytes and Keratinocytes against UVB-Induced DNA Damage In Vivo

Abstract

UVR promotes skin cancer through multiple mechanisms, including induction of inflammation, oxidative stress, and DNA damage such as 8-oxoguanine and cyclobutane pyrimidine dimers. We investigated whether the anti-inflammatory activities of aspirin (acetylsalicylic acid [ASA]) could protect against UVB-induced DNA damage and skin carcinogenesis. ASA reduced UVB-induced 8-oxoguanine and cyclobutane pyrimidine dimers in Melan-A melanocytes and HaCaT keratinocytes. Skin from UVB-irradiated C57BL/6 mice receiving 0.4 mg ASA daily by gavage exhibited less inflammation, fewer sunburn cells, and reduced 8-oxoguanine lesions than skin from irradiated control animals. ASA similarly reduced UVB-induced sunburn cells, 8-oxoguanine, and cyclobutane pyrimidine dimer lesions in skin of melanoma-prone TN 61R mice, and this was associated with decreased prostaglandin E 2 in plasma and skin. These effects of ASA, however, did not delay melanoma onset in TN 61R mice exposed to a single neonatal dose of UVB. In SKH1-E mice prone to squamous cell carcinoma, ASA reduced plasma and skin prostaglandin E 2 levels and indices of UVB-induced DNA damage and delayed squamous cell carcinoma onset induced by chronic UVB. These results indicate that ASA can protect against UVB-induced inflammation in skin and reduce UVB-induced DNA damage in both melanocytes and keratinocytes. These effects translated into greater chemopreventive efficacy for UVB-induced squamous cell carcinoma than melanoma mouse models.

Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage

“…In support of the concept that prostaglandin signalling influences fibroblast survival, specific inhibition of COX-2 immediately after UVB exposure significantly reduced fibroblast depletion and neutrophil recruitment. This is consistent with the observation that the COX enzyme inhibitor aspirin (acetylsalicylic acid) efficiently protects keratinocytes and melanocytes from acute UVB-induced DNA damage by decreasing cutaneous inflammation and PGE-2 levels in skin ( Rahman et al, 2021 ). Based on our findings, aspirin may also enhance dermal fibroblast survival and regeneration upon UVR-induced environmental stress.…”

Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation induced tissue damage

“…In support of the concept that prostaglandin signalling influences fibroblast survival, specific inhibition of COX-2 immediately after UVB exposure significantly reduced fibroblast depletion and neutrophil recruitment. This is consistent with the observation that the COX enzyme inhibitor aspirin (acetylsalicylic acid) efficiently protects keratinocytes and melanocytes from acute UVB-induced DNA damage by decreasing cutaneous inflammation and PGE-2 levels in skin (56). Based on our findings, aspirin may also enhance dermal fibroblast survival and regeneration upon UVR induced environmental stress.…”

Geroscience‐guided repurposing of FDA‐approved drugs to target aging: A proposed process and prioritization

“…Further investigation on other gerotherapeutics indicates that they target common mechanisms within each hallmark of aging, which includes scavenging of ROS and thereby oxidative stress by metformin in human immune cells, rapamycin in erythrocytes, MB in rat hearts, aspirin in endothelial cells, and NAC in the brain (Duicu et al, 2017; Garg et al, 2018; Hartwig et al, 2021; Jorda et al, 2020; Singh et al, 2016). Moreover, metformin, rapamycin, and aspirin further protect against DNA damage either via lowering DNA‐damage accumulation (rapamycin and aspirin) or upregulating DNA‐damage response (metformin) (Chen et al, 2011; Kulkarni et al, 2020; Rahman et al, 2021; Saha et al, 2014). SGLT2i improves mitochondrial function by preventing calcium buildup, while metformin and MB regulate the electron transport chain (Chen et al, 2021; Duicu et al, 2017; Olgar et al, 2020; Xiong et al, 2017).…”