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Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)

Cisplatin (CDDP) is currently employed for the treatment of several solid tumors, but cellular heterogeneity and the onset of drug resistance dictate that suitable biomarkers of CDDP sensitivity are established. Studies on triple-negative breast cancer (TNBC) have recently confirmed the involvement...

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Autores principales: Pompella, Alfonso, Corti, Alessandro, Visvikis, Athanase
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163661/
https://www.ncbi.nlm.nih.gov/pubmed/35669424
http://dx.doi.org/10.3389/fonc.2022.920316
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author Pompella, Alfonso
Corti, Alessandro
Visvikis, Athanase
author_facet Pompella, Alfonso
Corti, Alessandro
Visvikis, Athanase
author_sort Pompella, Alfonso
collection PubMed
description Cisplatin (CDDP) is currently employed for the treatment of several solid tumors, but cellular heterogeneity and the onset of drug resistance dictate that suitable biomarkers of CDDP sensitivity are established. Studies on triple-negative breast cancer (TNBC) have recently confirmed the involvement of gamma-glutamyltransferase 1 (GGT1), whose enzyme activity expressed at the cell surface favors the cellular resupply of antioxidant glutathione (GSH) thus offering cancer cells protection against the prooxidant effects of CDDP. However, an additional well-established mechanism depends on GGT1-mediated matabolism of extracellular GSH. It was in fact shown that glycyl-cysteine – the dipeptide originated by GGT1-mediated GSH metabolism at the cell surface – can promptly form adducts with exogenous CDDP, thus hindering its access to the cell, interactions with DNA and overall cytotoxicity. Both mechanisms: mainainance of intracellular GSH levels plus extracellular CDDP detoxication are likely concurring to determine GGT1-dependent CDDP resistance.
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spelling pubmed-91636612022-06-05 Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1) Pompella, Alfonso Corti, Alessandro Visvikis, Athanase Front Oncol Oncology Cisplatin (CDDP) is currently employed for the treatment of several solid tumors, but cellular heterogeneity and the onset of drug resistance dictate that suitable biomarkers of CDDP sensitivity are established. Studies on triple-negative breast cancer (TNBC) have recently confirmed the involvement of gamma-glutamyltransferase 1 (GGT1), whose enzyme activity expressed at the cell surface favors the cellular resupply of antioxidant glutathione (GSH) thus offering cancer cells protection against the prooxidant effects of CDDP. However, an additional well-established mechanism depends on GGT1-mediated matabolism of extracellular GSH. It was in fact shown that glycyl-cysteine – the dipeptide originated by GGT1-mediated GSH metabolism at the cell surface – can promptly form adducts with exogenous CDDP, thus hindering its access to the cell, interactions with DNA and overall cytotoxicity. Both mechanisms: mainainance of intracellular GSH levels plus extracellular CDDP detoxication are likely concurring to determine GGT1-dependent CDDP resistance. Frontiers Media S.A. 2022-05-20 /pmc/articles/PMC9163661/ /pubmed/35669424 http://dx.doi.org/10.3389/fonc.2022.920316 Text en Copyright © 2022 Pompella, Corti and Visvikis https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Pompella, Alfonso
Corti, Alessandro
Visvikis, Athanase
Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)
title Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)
title_full Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)
title_fullStr Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)
title_full_unstemmed Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)
title_short Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)
title_sort redox mechanisms in cisplatin resistance of cancer cells: the twofold role of gamma-glutamyltransferase 1 (ggt1)
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163661/
https://www.ncbi.nlm.nih.gov/pubmed/35669424
http://dx.doi.org/10.3389/fonc.2022.920316
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