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Multiple roles of glyoxalase 1-mediated suppression of methylglyoxal glycation in cancer biology—involvement in tumour suppression, tumour growth, multidrug resistance and target for chemotherapy
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Rabbani, Naila, Xue, Mingzhan, Weickert, Martin O. and Thornalley, Paul J. (2018) Multiple roles of glyoxalase 1-mediated suppression of methylglyoxal glycation in cancer biology—involvement in tumour suppression, tumour growth, multidrug resistance and target for chemotherapy. Seminars in Cancer Biology, 49 . pp. 83-93. doi:10.1016/j.semcancer.2017.05.006
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WRAP-multiple-roles-glyoxalase 1-mediated-suppression-methylglyoxal-glycation-cancer-biology-Rabbani-2017.pdf - Accepted Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (822Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/j.semcancer.2017.05.006
Abstract
Glyoxalase 1 (Glo1) is part of the glyoxalase system in the cytoplasm of all human cells. It catalyses the glutathione-dependent removal of the endogenous reactive dicarbonyl metabolite, methylglyoxal (MG). MG is formed mainly as a side product of anaerobic glycolysis. It modifies protein and DNA to form mainly hydroimidazolone MG-H1 and imidazopurinone MGdG adducts, respectively. Abnormal accumulation of MG, dicarbonyl stress, increases adduct levels which may induce apoptosis and replication catastrophe. In the non-malignant state, Glo1 is a tumour suppressor protein and small molecule inducers of Glo1 expression may find use in cancer prevention. Increased Glo1 expression is permissive for growth of tumours with high glycolytic activity and is thereby a biomarker of tumour growth. High Glo1 expression is a cause of multi-drug resistance. It is produced by over-activation of the Nrf2 pathway and GLO1 amplification. Glo1 inhibitors are antitumour agents, inducing apoptosis and necrosis, and anoikis. Tumour stem cells and tumours with high flux of MG formation and Glo1 expression are sensitive to Glo1 inhibitor therapy. It is likely that MG-induced cell death contributes to the mechanism of action of current antitumour agents. Common refractory tumours have high prevalence of Glo1 overexpression for which Glo1 inhibitors may improve therapy.
| Item Type: | Journal Article | ||||||||
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| Subjects: | R Medicine > RC Internal medicine | ||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science > Centre for Systems Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Cancer -- Prevention, Cancer -- Chemotherapy, Gene amplification, Apoptosis | ||||||||
| Journal or Publication Title: | Seminars in Cancer Biology | ||||||||
| Publisher: | Academic Press | ||||||||
| ISSN: | 1044-579X | ||||||||
| Official Date: | April 2018 | ||||||||
| Dates: |
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| Date of first compliant deposit: | 10 January 2018 | ||||||||
| Volume: | 49 | ||||||||
| Page Range: | pp. 83-93 | ||||||||
| DOI: | 10.1016/j.semcancer.2017.05.006 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access |
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