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Differential photoprotective effects of 1,25-dihydroxyvitamin D3 and a low calcaemic deltanoidContribution to the Vitamin D Update collected papers
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 l...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Online Access: | Get full text |
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| Summary: | 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.
Here we show that a low-calcaemic vitamin D analogue, QW, is photoprotective
in vitro
and
in vivo
. Like the active vitamin D hormone, 1,25-dihydroxyvitamin D3, QW protects against ultraviolet radiation-induced cell loss, DNA damage and immunosuppression. |
|---|---|
| ISSN: | 1474-905X 1474-9092 |
| DOI: | 10.1039/c2pp25208b |