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

作者：Dixon Katie M; Sequeira Vanessa B; Deo Shivashni S; Mohan Ritu; Posner Gary H; Mason Rebecca S^*

来源：Photochemical and Photobiological Sciences, 2012, 11(12): 1825-1830.

DOI：10.1039/c2pp25208b

We have previously demonstrated that the active vitamin D hormone, 1 alpha,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, 1 alpha-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 rho mol 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 rho mol cm(-2)) was not as effective as 1 alpha,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.

• 出版日期2012