Page 196 - Vitamin D and Cancer

8 Vitamin D and Cancer Chemoprevention 183

treated with 5 mg/kg diet of 1,25(OH) D . The tumor multiplicity was reduced by
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85% in the 2.5 mg/kg diet of 1,25(OH) D cohort and by 98% in the 5 mg/kg diet of
2 3
1,25(OH) D cohort. Although there was a reduction in both the tumor incidence
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and multiplicity, both groups had toxicities associated with treatment including
weight loss and kidney calcium deposits. However, the authors demonstrated that
the toxicities were ameliorated when 9-cis retinoic acid (15 mg/kg diet) was added
to the diet.
In addition to examining how vitamin D effects tumor progression, Nakagawa
et al. published a study examining 1,25(OH) D ’s ability to prevent metastasis [29].
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The ability of Lewis lung carcinoma (LCC) cells to metastasize to the lungs follow-
ing intravenous injection were evaluated in syngenic vitamin D receptor (VDR)
−/−
−/−
null mutant (VDR ) mice and VDR wild-type (VDR ) mice. VDR mice on a
+/+
normal diet (1.2% calcium, 0.6% phosphorus and 108 IU vitamin D /100 g diet)
3
exhibit hypocalcemia and had extremely high serum levels of 1,25(OH) D . The
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authors hypothesized that the high serum levels would inhibit metastatic growth of
the LCC cells. To test this hypothesis the hypocalcemia, and/or hypervitaminosis D
were corrected in the VDR mice using dietary manipulations. The results demon-
−/−
strated that the metastatic growth of LCC cells was greatly reduced in the VDR in
−/−
response to the high serum levels of 1,25(OH) D , suggesting high serum levels of
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1,25(OH) D may act to prevent lung metastasis. Although these studies do demon-
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strate that vitamin D has the potential to act as a chemopreventive agent in lung
cancer, further studies are required to elucidate optimal formulation, dosing and
administration methods to translate its usefulness in the clinic. In addition, more
information about how vitamin D deficient versus sufficient diets effect the pro-
gression of lung cancer will also aid in elucidating the chemopreventive nature of
vitamin D.

8.2.5 All Other Cancers

The chemopreventive nature of vitamin D is starting to be investigated in a number
of other cancer subtypes that are less commonly studied, however few published
studies exist to date. This section will summarize the one or two published studies
that are available for melanoma, and retinoblastoma.
There is strong evidence that UV-B radiation that results in the synthesis of
vitamin D in the skin also contributes to the development of melanoma [30].
Although UV-B exposure is a major contributor to vitamin D status, supplementa-
tion with dietary vitamin D is being suggested as a safer approach for populations
at risk of melanoma. However, more recently studies are being conducted to exam-
ine if vitamin D may play a role in reducing some of the damaging effects associ-
ated with UV-B exposure, for example a study by Dixon et al. examined the use of
a topical treatment of 0.33 mM 1,25(OH) D in Skh:HR1 mice [31]. The Skh:HR1
2
3
mice are hairless mice that form skin cancer following UV-B radiation. Mice were
either untreated, treated with 1,25(OH) D pre and post UV-B exposure or treated
2 3