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Differential photoprotective effects of 1,25-dihydroxyvitamin D3 and a low calcaemic deltanoid

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Abstract

We have previously demonstrated that the active vitamin D hormone, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and a cis-locked non-genomic analogue, protect skin cells from ultraviolet radiation (UV)-induced skin cell loss, DNA damage, immunosuppression and skin carcinogenesis. Herein, we used a low-calcaemic analogue, 1α-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitamin D3 (QW), which has some transactivating capacity and is approximately 80–100 times less calcaemic than 1,25(OH)2D3. QW (0.1–10 nM) significantly (p < 0.05–0.01) reduced UV-induced DNA lesions (CPD) in skin fibroblasts and keratinocytes and reduced cell death after UV exposure. Moreover, both 1,25(OH)2D3 and QW (1 nM) were equally effective in significantly (p < 0.01) increasing levels of tumour suppressive p53 in cultured human keratinocytes at 3 and 6 h after UV exposure. In a hairless mouse model, both 1,25(OH)2D3 and QW (22.8 ρmol cm−2) reduced UV-immunosuppression from 13.7 ± 1.3% to 0.1 ± 1.1% (p < 0.01) and 5.4 ± 1.5% (p < 0.01) respectively. When tested alongside 1,25(OH)2D3 in a murine model of skin carcinogenesis. QW (22.8 ρmol cm−2) was not as effective as 1α,25(OH)2D3 or a cis-locked analogue in reducing tumour formation or inhibiting tumour progression. It is possible that the dose required for QW to be effective as an anti-photocarcinogenesis agent in vivo is higher than for protection against the acute effects of UV exposure, but the dissociation between clear acute photo-protective effects and limited long term photoprotection is as yet unexplained.

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Authors and Affiliations

  1. Discipline of Physiology, Bosch Institute, School of Medical Sciences, University of Sydney, NSW, Australia

    Katie M. Dixon, Vanessa B. Sequeira, Shivashni S. Deo, Ritu Mohan & Rebecca S. Mason

  2. Department of Chemistry, School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland, 21218, USA

    Gary H. Posner

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  1. Katie M. Dixon
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  2. Vanessa B. Sequeira
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  3. Shivashni S. Deo
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  4. Ritu Mohan
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  5. Gary H. Posner
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  6. Rebecca S. Mason
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Correspondence to Rebecca S. Mason.

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Contribution to the Vitamin D Update collected papers.

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Dixon, K.M., Sequeira, V.B., Deo, S.S. et al. Differential photoprotective effects of 1,25-dihydroxyvitamin D3 and a low calcaemic deltanoid. Photochem Photobiol Sci 11, 1825–1830 (2012). https://doi.org/10.1039/c2pp25208b

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  • DOI: https://doi.org/10.1039/c2pp25208b

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