Methylglyoxal displays colorectal cancer-promoting properties in the murine models of azoxymethane and CT26 isografts

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Methylglyoxal (MG), a highly reactive carbonyl species (RCS) with pro-oxidant and proinflammatory properties, may be a colon tumor-promoting factor in food and biological systems. In the present study, we found that consumption of MG significantly deteriorated azoxymethane (AOM)-induced colonic preneoplastic lesions in ICR mice, in which biomarkers of oxidative stress and inflammation within the body and feces induced by MG-fueled carbonyl stress may have played important roles. Interestingly, exposure to MG also led to increases in the serum low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio and fecal bile acid levels in mice, which may be critical factors involved in MG-induced colonic lesions. Additionally, MG treatment (50 mg/kg body weight (BW); intraperitoneally) promoted tumor growth of CT26 isografts in mice partly by carbonyl stress-evoked protumorigenic responses, including low-grade inflammation and oxidative stress. Furthermore, primary tumor cells isolated from mice with MG-induced CT26 isografts had greater proliferative and migratory activities as well as stem-like properties compared to those isolated from the vehicle controls. Excitingly, enhanced expression or activation of proteins that modulate cell survival, proliferation, or migration/invasion was also observed in those cells. In conclusion, it is conceivable that MG-induced carbonyl stress may be the pivotal promoter involved in colon cancer progression.Graphical abstractThe effect of MG-induced carbonyl stress on colon cancer progression.HighlightsOral or intraperitoneal administration of methylglyoxal leads to pathogenic carbonyl stress.Methylglyoxal-induced carbonyl stress results in oxidative stress and inflammation in vivo.Methylglyoxal-induced carbonyl stress deteriorates colonic preneoplastic lesions.Methylglyoxal-induced carbonyl stress enhances malignancy of colon tumor.

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