Oral and Poster Presentation 18th International Congress on Photobiology 2024

Cyclic AMP-regulatory element-binding protein: A novel early marker that could predict the efficacy of sun protective agents in reducing skin carcinogenesis. (#152)

Julianne C Nayar 1 , Furkan A Ince 1 , Myriam Abboud 2 , Rebecca S Mason 3 , Katie M Dixon 1
  1. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
  2. Department of Health, Zayed University, Abu Dhabi, United Arab Emirates
  3. School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, NSW, Australia

Australia and New Zealand have the highest skin cancer rates worldwide, despite ongoing sun safety campaigns. It is therefore necessary to enhance current photoprotective measures. We have demonstrated that active vitamin D compound, 1,25-dihydroxyvtamin D3 (1,25D), and structurally related compounds including 20-hydroxyvitamin D (20D), 1,25-dihydroxylumisterol (JN), QW-1624F2-2 (QW) and tetrahydrocurcumin (THC) are novel photoprotective agents. It has generally been accepted that agents capable of protecting against acute markers of ultraviolet radiation (UVR)-induced damage such as DNA damage and immunosuppression, would provide protection against chronic UVR damage in a 40-week murine photocarcinogenesis protocol. Several photoprotective agents including 20D and QW, however, have proven otherwise. Therefore, markers of acute UVR-induced damage are not reliable predictors to predict the ability of a photoprotective agent to protect against photocarcinogenesis. Phosphorylated Cyclic AMP-regulatory element-binding protein (pCREB) is a transcription factor that is overexpressed in skin cancer. We have shown that UVR increases pCREB levels in melanocytes and keratinocytes. Considering this, pCREB may be a potential predictor of the ability of a photoprotective agent to protect against photocarcinogenesis. Our studies in primary human dermal fibroblasts showed that 1,25D treatment immediately after UVR exposure significantly reduced pCREB levels (p < 0.05). This was supported by in vivo studies showing significant reductions in UVR-induced pCREB levels in Skh:hr1 mouse skin following topical application of 1,25D or related vitamin D compounds JN and THC (p < 0.01). Conversely, compound 20D, which did not prevent photocarcinogenesis, did not prevent UVR-induced increase in pCREB (p = ns). Preliminary studies in ex vivo human skin have demonstrated a similar trend with 1,25D treatment causing reductions in pCREB levels following UVR exposure. These results demonstrate that pCREB may potentially be a predictor of photocarcinogenesis and could streamline the process of identifying suitable photoprotective agents for a 40-week photocarcinogenesis model.