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Int. J. Mol. Sci. 2017, 18(1), 213; doi:10.3390/ijms18010213

Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer

1
Metastasis Research Laboratory, GIGA-Cancer, University of Liège, 4000 Liège, Belgium
2
Department of Pathology, Liège University Hospital, 4000 Liège, Belgium
3
Department of Nuclear Medicine, Erasme University Hospital, Université Libre de Bruxelles, 1050 Bruxelles, Belgium
4
Nuclear Medicine and Oncological Imaging Division, Medical Physics Department, Liège University Hospital, 4000 Liège, Belgium
5
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, 1050 Bruxelles, Belgium
6
Laboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 13-8654, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Casper G. Schalkwijk
Received: 30 November 2016 / Revised: 6 January 2017 / Accepted: 12 January 2017 / Published: 21 January 2017
(This article belongs to the Special Issue Glyoxalase System)
View Full-Text   |   Download PDF [8658 KB, uploaded 21 January 2017]   |  

Abstract

Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and induces the formation of advanced glycation end-products that are implicated in several pathologies including cancer. All mammalian cells have an enzymatic defense against MG composed by glyoxalases GLO1 and GLO2 that converts MG to d-lactate. Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality. In this study, we used immunohistochemistry to examine the level of MG protein adducts, in a series of 102 CRC human tumors divided into four clinical stages. We consistently detected a high level of MG adducts and low GLO1 activity in high stage tumors compared to low stage ones suggesting a pro-tumor role for dicarbonyl stress. Accordingly, GLO1 depletion in CRC cells promoted tumor growth in vivo that was efficiently reversed using carnosine, a potent MG scavenger. Our study represents the first demonstration that MG adducts accumulation is a consistent feature of high stage CRC tumors. Our data point to MG production and detoxification levels as an important molecular link between exacerbated glycolytic activity and CRC progression. View Full-Text
Keywords: methylglyoxal; colorectal cancer; MG-adducts; glyoxalase 1; 18F-Fluorodeoxyglucose (18F-FDG) methylglyoxal; colorectal cancer; MG-adducts; glyoxalase 1; 18F-Fluorodeoxyglucose (18F-FDG)
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Chiavarina, B.; Nokin, M.-J.; Bellier, J.; Durieux, F.; Bletard, N.; Sherer, F.; Lovinfosse, P.; Peulen, O.; Verset, L.; Dehon, R.; Demetter, P.; Turtoi, A.; Uchida, K.; Goldman, S.; Hustinx, R.; Delvenne, P.; Castronovo, V.; Bellahcène, A. Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer. Int. J. Mol. Sci. 2017, 18, 213.

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