Hormetic potential of methylglyoxal, a side-product of glycolysis, in switching tumours from growth to death
Autor: | David Spiegel, Koji Uchida, Craig A. Hutton, Justine Bellier, Akeila Bellahcene, Florence Durieux, Olivier Peulen, Marie-Julie Nokin, Vincenzo Castronovo, James R. Cochrane |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Glycation End Products
Advanced 0301 basic medicine NF-E2-Related Factor 2 lcsh:Medicine Article 03 medical and health sciences chemistry.chemical_compound Lactoylglutathione lyase Hormesis 0302 clinical medicine Glycation Cell Line Tumor Neoplasms Humans Glycolysis lcsh:Science Cell Proliferation Multidisciplinary Cell Death biology Cell growth Methylglyoxal lcsh:R Lactoylglutathione Lyase Pyruvaldehyde 030104 developmental biology chemistry Biochemistry Anaerobic glycolysis 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research lcsh:Q Glyoxalase system |
Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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