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

• Published in: Photochemical & photobiological sciences 2012-12, Vol.11 (12), p.1825-1830
• Main Authors: Dixon, Katie M., Sequeira, Vanessa B., Deo, Shivashni S., Mohan, Ritu, Posner, Gary H., Mason, Rebecca S.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - radiation effects; Biochemistry; Biomaterials; Calcitriol - analogs & derivatives; Calcitriol - pharmacology; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - radiation effects; Cells, Cultured; Chemistry; DNA Damage - drug effects; DNA Damage - radiation effects; Humans; Immunosuppression; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - radiation effects; Mice; Mice, Hairless; Physical Chemistry; Plant Sciences; Radiation-Protective Agents - pharmacology; Skin - drug effects; Skin - radiation effects; Tumor Suppressor Protein p53 - metabolism; Ultraviolet Rays
• ISSN: 1474-905X; 1474-9092
• DOI: 10.1039/c2pp25208b

We have previously demonstrated that the active vitamin D hormone, 1α,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) 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) 2 D 3 . 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) 2 D 3 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) 2 D 3 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) 2 D 3 in a murine model of skin carcinogenesis. QW (22.8 ρmol cm −2 ) was not as effective as 1α,25(OH) 2 D 3 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.