Cancer Chemotherapy and Pharmacology

, Volume 75, Issue 1, pp 1–15 | Cite as

Cytoprotective and regulatory functions of glutathione S-transferases in cancer cell proliferation and cell death

Review Article

Abstract

Purpose

Glutathione S-transferases (GSTs) family of enzymes is best known for their cytoprotective role and their involvement in the development of anticancer drug resistance. Recently, emergence of non-detoxifying properties of GSTs has provided them with significant biological importance. Addressing the complex interactions of GSTs with regulatory kinases will help in understanding its precise role in tumor pathophysiology and in designing GST-centered anticancer strategies.

Methods

We reviewed all published literature addressing the detoxification and regulatory roles of GSTs in the altered biology of cancer and evaluating novel agents targeting GSTs for cancer therapy.

Results

The role of GSTs, especially glutathione S-transferase P1 isoform in tumoral drug resistance, has been the cause of intense debate. GSTs have been demonstrated to interact with different protein partners and modulate signaling pathways that control cell proliferation, differentiation and apoptosis. These specific functions of GSTs could lead to the development of new therapeutic approaches and to the identification of some interesting candidates for preclinical and clinical development. This review focuses on the crucial role played by GSTs in the development of resistance to anticancer agents and the major findings regarding the different modes of action of GSTs to regulate cell signaling.

Keywords

Glutathione S-transferase Polymorphism Detoxification Signaling Apoptosis 

Abbreviations

GST

Glutathione S-transferase

GSH

Glutathione

GSTP1

Glutathione S-transferase P1

MRP

Multidrug resistance protein

ROS

Reactive oxygen species

JNK

c-Jun N-terminal kinase

MAP kinase

Mitogen-activated protein kinase

ASK

Apoptosis signal-regulating kinase

PKA

Protein kinase A

PKC

Protein kinase C

EGFR

Epidermal growth factor receptor

FANCC

Fanconi anemia group c DNA repair protein

TGM2

Transglutaminase

STAT

Signal transducer and activator of transcription

1-Cys-Prx

1-Cysteine peroxiredoxin

NO

Nitric oxide

EA

Ethacrynic acid

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Biotechnology, School of Engineering and TechnologySharda UniversityGreater NoidaIndia

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