Chemoprevention of chemically-induced mammary and colon carcinogenesis by 1α-hydroxyvitamin D5

In the colon, 1α(OH)D5 (25 μg/kg diet) was highly effective (p < 0.001) in inhibiting the development of azoxymethane (AOM)-induced Aberrant crypt foci (ACF) in CF-1 mice. Studies on the stage specific inhibitory effects of 1α(OH)D5 in the colon demonstrated that animals receiving 1α(OH)D5 (25 μg/kg diet) during the initiation, promotion, and entire period had a reduction in ACF number of 71, 80 and 82%, respectively. Immunohistochemistry studies comparing the colons of animals receiving control versus 1α(OH)D5 supplemented diets showed that 1α(OH)D5 partly mediates its effects by regulating members of the oncogenic β-catenin pathway. 1α(OH)D5 inhibited expression of β-catenin and peroxisome proliferator-activated receptor β, a β-catenin-TCF-4 responsive gene, whereas it induced expression of VDR. Cumulatively, these studies support the chemopreventive properties of 1α(OH)D5 against the development of breast and colon cancers.