Combination photodynamic therapy (cPDT) in which vitamin D (VD) is given prior to aminolevulinate, a precursor
(pro-drug) for protoporphyrin IX (PpIX), is an approach developed in our laboratory. We previously showed that 1α,25-
dihydroxyvitamin D3 (calcitriol), given prior to PDT, enhances accumulation of PpIX and improves cell death post-PDT
in a mouse skin cancer model. However, since calcitriol poses a risk for hypercalcemia, we replaced systemic calcitriol
with oral cholecalciferol (D3), administered as a high (tenfold, “10K”) diet over a ten-day period. Here, we ask whether
VD deficiency might alter the response to cPDT. Nude mice were fed a VD-deficient diet for at least 4 weeks
(“deficient”); controls were fed a normal 1,000 IU/kg diet (“1K”). Human A431 cells were implanted subcutaneously
and mice were switched to the 10K diet or continued on their baseline diets (controls). In other experiments, mice
received a human equivalent dose of 50,000 IU D3 by oral gavage, to simulate administration of a single, high-dose VD
pill. At various times, tumors were harvested and serum was collected to measure levels of VD metabolic intermediates.
A significant increase in PpIX levels and in the expression of differentiation and proliferation markers in tumor tissue
was observed after VD supplementation of both the deficient and 1K mice. Further results describing mechanistic details
of PpIX enhancement through alteration of heme- and VD-metabolic enzyme levels will be presented. Based on these
results, a clinical study using oral vitamin D prior to PDT for human skin cancer should be performed.