Gamma‐tocopherol but not mixed tocopherols attenuates moderate colon inflammation and inflammation‐promoted colon tumorigenesis in mice

Abstract

Inflammation promotes cancer development. Gamma‐tocopherol (γT), the predominant form of vitamin E in US diets, is shown to have anti‐inflammatory activities. Here we examined anticancer efficacy of γT and a mixture of tocopherols against colon cancer which is induced by azoxymethane (AOM, 10mg/kg) and promoted by severe or moderate inflammation through varied concentrations or cylces of dextran sodium sulfate (DSS) in male BALB/c mice. When AOM‐induced tumorigenesis was promoted by 3‐cycle DSS (1.5–2.5%), supplementation of γT or mixed tocopherols (at 1000mg/kg diet) had no effects on tumor incidence or size. Consistently, γT did not attenuate colon inflammation induced by 3‐cycle 2.5% DSS. In contrast, when AOM‐induced carcinogenesis was promoted by relatively mild one‐cycle 1.5% DSS, supplementation with γT but not mixed tocopherols suppressed the incidence of macroscopic adenomas (P=0.06) and significantly decreased polps with size larger than 2mm2 (P<0.05). γT also significantly reduced the number of polps (>2mm2) by a 2‐ cycle, 1.5% DSS treatment even when the supplementation started after AOM injection. All the polyps had enhanced translocation of beta‐catenin from membrane (in normal tissues) to the cytosol or nucleus. Furthermore, γT but not mixed tocopherols significantly attenuated DSS (1.5%)‐induced colon inflammation and tissue damage, as indicated by clinical scoring feces and histological evaluation of colon tissues. Our study supports a role of γT in chemoprevention of colon cancer via suppression of moderate inflammation.