A 116-kDa phytoglycoprotein inhibits aberrant crypt foci formation through modulation of manganese superoxide dismutase, inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-kappa B, activator protein-1, and proliferating cell nuclear antigen in 1,2-dimethylhydrazine/dextran sodium sulfate-treated ICR mice

Abstract

The 116-kDa Ulmus davidiana Nakai (UDN) glycoprotein is a naturally occurring phytoglycoprotein found in the stem of UDN. In this study, we investigated the chemopreventive effect of UDN glycoprotein on inflammation-mediated colorectal carcinogenesis induced by 10 mg/kg 1,2-dimethylhydrazine and 2% dextran sodium sulfate in ICR mice. Consumption of UDN glycoprotein (0.01 and 0.02%) significantly reduced the frequency of colonic aberrant crypt foci, the expression of colonic proliferating cell nuclear antigen, and the release of plasma lactate dehydrogenase without any cytotoxic activity at the initiation stage of colorectal carcinogenesis in 1,2-dimethylhydrazine/dextran sodium sulfate-treated mice. In addition, UDN glycoprotein has antioxidative effects on the formation of plasma thiobarbituric acid reactive substances and on the production of plasma inducible nitric oxide, accompanying the normalizing effects on the activity of colonic antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in the mice. UDN glycoprotein intake also remarkably attenuated the expression of inflammation-related factors (inducible nitric oxide synthase and cyclooxygenase-2) and the DNA-binding activity of redox-sensitive transcription factors (nuclear factor-kappa B and activator protein-1) in the mice. Collectively, the results suggest that UDN glycoprotein has chemopreventive potential at the initiation stage of colorectal cancer by reducing the factors responsible for oxidative stress, inflammation, and carcinogenesis.