[en] Metabolic reprogramming toward aerobic glycolysis unavoidably favours methylglyoxal (MG) and advanced glycation end products (AGEs) formation in cancer cells. MG was initially considered a highly cytotoxic molecule with potential anti-cancer value. However, we have recently demonstrated that MG enhanced tumour growth and metastasis. In an attempt to understand this dual role, we explored MG-mediated dicarbonyl stress status in four breast and glioblastoma cancer cell lines in relation with their glycolytic phenotype and MG detoxifying capacity. In glycolytic cancer cells cultured in high glucose, we observed a significant increase of the conversion of MG to D-lactate through the glyoxalase system. Moreover, upon exogenous MG challenge, glycolytic cells showed elevated amounts of intracellular MG and induced de novo GLO1 detoxifying enzyme and Nrf2 expression. Thus, supporting the adaptive nature of glycolytic cancer cells to MG dicarbonyl stress when compared to non-glycolytic ones. Finally and consistent with the pro-tumoural role of MG, we showed that low doses of MG induced AGEs formation and tumour growth in vivo, both of which can be reversed using a MG scavenger. Our study represents the first demonstration of a hormetic effect of MG defined by a low-dose stimulation and a high-dose inhibition of tumour growth.
Research Center/Unit :
Giga-Cancer - ULiège
Disciplines :
Oncology Microbiology
Author, co-author :
Nokin, Marie-Julie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Bellier, Justine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Peulen, Olivier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Uchida, Koji
Spiegel, David A.
Cochrane, James R.
Hutton, Craig A.
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Language :
English
Title :
Hormetic potential of methylglyoxal, a side-product of glycolysis, in switching tumours from growth to death.
Publication date :
2017
Journal title :
Scientific Reports
eISSN :
2045-2322
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
7
Issue :
1
Pages :
11722
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique Télévie CAC - Centre anticancéreux près l'Université de Liège asbl ULiège FSR - Université de Liège. Fonds spéciaux pour la recherche
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