Skin cancer prevention: A possible role of 1,25dihydroxyvitamin D3 and its analogs

Abstract We previously reported that the natural hormone 1,25dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) protects human skin cells from ultraviolet radiation (UVR)-induced apoptosis. UVR-induced pre-mutagenic cyclobutane pyrimidine dimers are diminished in number from 0.5 h after cessation of UVR in all skin cell types, by treatment with three different Vitamin D compounds: by 1,25(OH) 2 D 3 , by the rapid acting, low calcemic analog, 1α,25(OH) 2 lumisterol 3 (JN) and by the low calcemic but transcriptionally active hybrid analog 1α-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitamin D3 QW-1624F2-2 (QW), which may explain the enhanced cell survival. The rapid response antagonist analog 1β,25(OH) 2 D 3 (HL) abolished the photoprotective effects of 1,25(OH) 2 D 3 whilst a genomic antagonist, (23S)-25-dehydro-1α-hydroxyvitamin D 3 –26,23-lactone (TEI-9647), had no effect. UVR increased p53 expression in human skin cells, whilst concurrent treatment with 1,25(OH) 2 D 3 further enhanced this effect several fold, at 3 and 6 h after UVR. Combined with previously reported lower nitrite levels with 1,25(OH) 2 D 3 , this increased p53 expression may favor DNA repair over apoptosis. We now report that topical application of 1,25(OH) 2 D 3 or QW also suppressed solar simulated UV (SSUVR-induced pyrimidine dimers in the epidermis of irradiated hairless Skh:HR1 mice, measured 24 h after irradiation. Furthermore, UVR-induced immunosuppression in the mice was markedly reduced by topical application of either 1,25(OH) 2 D 3 or QW. These preliminary results show, for the first time, a protective effect of Vitamin D compounds against DNA photodamage in vivo.