The role of classical and novel forms of vitamin d in the pathogenesis and progression of nonmelanoma skin cancers

Andrzej T. Slominski, Anna A. Brożyna, Michal A. Zmijewski, Zorica Janjetovic, Tae Kang Kim, Radomir M. Slominski, Robert C. Tuckey, Rebecca S. Mason, Anton M. Jetten, Purushotham Guroji, Jörg Reichrath, Craig Elmets, Mohammad Athar

Research output: Chapter in Book/Conference paperChapter

2 Citations (Scopus)

Abstract

Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290–400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290–320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body’s requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
EditorsJörg Reichrath
PublisherSpringer Heidelberg
Pages257-283
Number of pages27
Edition3rd
ISBN (Electronic)978-3-030-46227-7
ISBN (Print)978-3-030-46226-0
DOIs
Publication statusPublished - 2020

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1268
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

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