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A vitamin D analog reduced UV generated skin cancer in mice – July 2011


{alpha},25(OH)2-vitamin D and a non-genomic vitamin D analog inhibit ultraviolet radiation-induced skin carcinogenesis.

Cancer Prev Res (Phila). 2011 Jul 6.
Dixon KM, Norman AW, Sequeira VB, Mohan R, Rybchyn MS, Reeve VE, Halliday GM, Mason RS.
1Discipline of Physiology and Bosch Institute, The University of Sydney.

Exposure to ultraviolet radiation (UVR) can lead to a range of deleterious responses in the skin. An important form of damage is the DNA photo-lesion cyclobutane pyrimidine dimer (CPD). CPDs can be highly mutagenic if not repaired prior to cell division and can lead to UVR-induced immunosuppression making them potentially carcinogenic. UVR exposure also produces vitamin D, a pre-hormone.

Different shapes of the steroid hormone, 1?,25-dihydroxyvitamin D3, 1,25(OH)2D3 can produce biological responses through binding either to its cognate nuclear receptor (VDR) to regulate gene transcription or to the VDR associated with plasma membrane caveolae to produce, via signal transduction, non-genomic physiological responses. Here we show that both 1,25(OH)2D3 and 1?,25(OH)2-lumisterol (JN), a conformationally restricted analog that can generate only non-genomic responses, are effective inhibitors of UVR damage in an immunocompetent mouse (Skh:hr1) model susceptible to UV-induced tumors. Both 1,25(OH)2D3 and JN significantly reduced UVR-induced CPD, apoptotic sunburn cells and immune suppression.

Furthermore, these compounds inhibited skin tumor development, both papillomas and squamous cell carcinomas, in these mice. The observed reduction of these UVR-induced effects by 1,25(OH)2D3 and JN suggests a role for these compounds in prevention against skin carcinogenesis.

To the best of our knowledge, this is the first comprehensive report of an in vivo long-term biological response generated by chronic dosing with a non-genomic-selective vitamin D steroid.

PMID: 21733837
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See also VitaminDWiki