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Mol. Cells

Published online September 28, 2022

© The Korean Society for Molecular and Cellular Biology

Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells

Ji-Young Kim1,4 , Ji-Hye Jung1,4 , Seung-Joon Lee1 , Seon-Sook Han1,* , and Seok-Ho Hong1,2,3,*

1Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea, 2Institute of Medical Science, School of Medicine, Kangwon National University, Chuncheon 24341, Korea, 3KW-Bio Co., Ltd., Wonju 26487, Korea, 4These authors contributed equally to this work.

Correspondence to : shhong@kangwon.ac.kr(SHH); ssunimd@kangwon.ac.kr(SSH)

Received: July 5, 2022; Revised: July 29, 2022; Accepted: August 1, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential anti-tumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathione-dependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

Keywords cancer, cancer stem cell, glyoxalase 1, methylglyoxal

Article

On-line First

Mol. Cells

Published online September 28, 2022

Copyright © The Korean Society for Molecular and Cellular Biology.

Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells

Ji-Young Kim1,4 , Ji-Hye Jung1,4 , Seung-Joon Lee1 , Seon-Sook Han1,* , and Seok-Ho Hong1,2,3,*

1Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea, 2Institute of Medical Science, School of Medicine, Kangwon National University, Chuncheon 24341, Korea, 3KW-Bio Co., Ltd., Wonju 26487, Korea, 4These authors contributed equally to this work.

Correspondence to:shhong@kangwon.ac.kr(SHH); ssunimd@kangwon.ac.kr(SSH)

Received: July 5, 2022; Revised: July 29, 2022; Accepted: August 1, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential anti-tumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathione-dependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

Keywords: cancer, cancer stem cell, glyoxalase 1, methylglyoxal

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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