E-cadherin Mediates the Preventive Effect of Vitamin D 3 in Colitis-associated Carcinogenesis

Abstract

Vitamin D 3 is beneficial in ameliorating or preventing inflammation and carcinogenesis. Here, we evaluated if vitamin D 3 has a preventive effect on colitis-associated carcinogenesis. Administration of azoxymethane (AOM), followed with dextran sulfate sodium (DSS), was used to simulate colitis-associated colon cancer in mice. The supplement of vitamin D 3 at different dosages (15, 30, 60 IU·g -1 ·w -1), started before AOM or immediately after DSS treatment (post 60), was sustained to the end of the experiment. Dietary vitamin D 3 significantly reduced the number of tumors and tumor burden in a dose-dependent manner. Of note, vitamin D 3 in high doses showed significant preventive effects on carcinogenesis regardless of administration before or after AOM-DSS treatment. Cell proliferation decreased in vitamin D 3 groups compared with the control group after inhibition of expression of β-catenin and its downstream target gene cyclin D1 in the colon. In vitro, vitamin D 3 reduced the transcriptional activity and nuclear level of β-catenin, and it also increased E-cadherin expression and its binding affinity for β-catenin. Moreover, repression of E-cadherin was rescued by supplemental vitamin D 3 in mouse colons. Taken together, our results indicate that vitamin D 3 effectively suppressed colonic carcinogenesis in the AOM-DSS mouse model. Our findings further suggest that upregulation of E-cadherin contributes to the preventive effect of vitamin D 3 on β-catenin activity.