Keratinocyte Carcinoma and Photoprevention: The Protective Actions of Repurposed Pharmaceuticals, Phytochemicals and Vitamins

Abstract

Ultraviolet radiation (UVR) arising from sun exposure represents a major risk factor in the development of keratinocyte carcinomas (KCs). UVR exposure induces dysregulated signal transduction, oxidative stress, inflammation, immunosuppression and DNA damage, all of which promote the induction and development of photocarcinogenesis. Because the incidence of KCs is increasing, better prevention strategies are necessary. In the concept of photoprevention, protective compounds are administered either topically or systemically to prevent the effects of UVR and the development of skin cancer. In this review, we provide descriptions of the pathways underlying photocarcinogenesis and an overview of selected photoprotective compounds, such as repurposed pharmaceuticals, plant-derived phytochemicals and vitamins. We discuss the protective potential of these compounds and their effects in pre-clinical and human trials, summarising the mechanisms of action involved in preventing photocarcinogenesis.

The Activation of PPARγ by (2Z,4E,6E)-2-methoxyocta-2,4,6-trienoic Acid Counteracts the Epithelial–Mesenchymal Transition Process in Skin Carcinogenesis

“…The rise in the incidence of keratinocyte carcinoma is an important public health concern, and research is continuing to aim at the development of an efficient cSCC treatment that combines higher clearance rates with few side effects, short treatment duration, and low costs. Cutaneous carcinogenesis is primarily mediated by UV exposure and is characterized by DNA damage and alterations of signaling pathways crucially involved in cell proliferation and survival, oxidative stress, inflammation, immunosuppression, differentiation, remodeling, and apoptosis [ 3 , 4 ]. Data in the literature on knockout mouse models suggest a protective role for PPARγ in keratinocyte-derived carcinoma.…”

“…Cutaneous squamous cell carcinoma (cSCC) is the most common keratinocyte-derived cancer with metastatic potential, and it is associated with poor prognosis in the advanced stage [ 1 , 2 ]. Ultraviolet radiation (UVR) is the main causative agent involved in the development of skin cancer through multiple mechanisms, including induction of inflammation, oxidative stress, immunosuppression, DNA damage, and dysregulated signal transduction [ 3 , 4 ].…”

Topical Brimonidine Delays Ultraviolet Radiation‐Induced Squamous Cell Carcinoma in Hairless Mice

“…It was beyond the scope of this paper to investigate the reason for the delay in photocarcinogenesis. However, it could be due to inhibition of DNA damage, oxidative stress, inflammation, immunosuppression and dysregulated signal transduction ( 21 ). After our study was ended, we investigated the possibility to estimate the Sun Protection Factor of the brimonidine formulations used in this study to investigate whether there was absorption of UVR by brimonidine.…”

Introduction to the Special Issue on “Keratinocyte Carcinomas: Biology and Evolving Non-Invasive Management Paradigms”

“…Pihl, C. et al [ 12 ] reviewed the photoprotective potential of various pharmaceuticals, phytochemicals and vitamins for prevention of KCs. Repurposed pharmaceutical compounds constitute a promising option for systemic photoprotection.…”