Glutathione -transferase π: a Potential Role in Antitumor Therapy

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2018 Nov 15

PMID 30425455

Citations 26

Authors

Shu-Chen Dong

Huan-Huan Sha

Xiao-Yue Xu

Tian-Mu Hu

Rui Lou

Huizi Li

Jian-Zhong Wu

Chen Dan

Jifeng Feng

Affiliations

Soon will be listed here.

Abstract

Glutathione -transferase π (GSTπ) is a Phase II metabolic enzyme that is an important facilitator of cellular detoxification. Traditional dogma asserts that GSTπ functions to catalyze glutathione (GSH)-substrate conjunction to preserve the macromolecule upon exposure to oxidative stress, thus defending cells against various toxic compounds. Over the past 20 years, abnormal GSTπ expression has been linked to the occurrence of tumor resistance to chemotherapy drugs, demonstrating that this enzyme possesses functions beyond metabolism. This revelation reveals exciting possibilities in the realm of drug discovery, as GSTπ inhibitors and its prodrugs offer a feasible strategy in designing anticancer drugs with the primary purpose of reversing tumor resistance. In connection with the authors' current research, we provide a review on the biological function of GSTπ and current developments in GSTπ-targeting drugs, as well as the prospects of future strategies.

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References

Qin F, Qin X, Zhang X, Jia H . [Expression and significance of P-glycoprotein, glutathione S-transferase-pi and Topoisomerase II in gastric carcinomas]. Ai Zheng. 2002; 21(2):167-70. View

Sau A, Filomeni G, Pezzola S, DAguanno S, Pellizzari Tregno F, Urbani A . Targeting GSTP1-1 induces JNK activation and leads to apoptosis in cisplatin-sensitive and -resistant human osteosarcoma cell lines. Mol Biosyst. 2011; 8(4):994-1006. DOI: 10.1039/c1mb05295k. View

Keefer L . Broad-Spectrum Anti-Cancer Activity of O-Arylated Diazeniumdiolates. For Immunopathol Dis Therap. 2011; 1(3):205-218. PMC: 3179376. DOI: 10.1615/ForumImmunDisTher.v1.i3.30. View

Raez L, Lilenbaum R . New developments in chemotherapy for advanced non-small cell lung cancer. Curr Opin Oncol. 2006; 18(2):156-61. DOI: 10.1097/01.cco.0000208789.37689.6b. View

Enoiu M, Aberkane H, Salazar J, Leroy P, Groffen J, Siest G . Evidence for the pro-oxidant effect of gamma-glutamyltranspeptidase-related enzyme. Free Radic Biol Med. 2000; 29(9):825-33. DOI: 10.1016/s0891-5849(00)00370-1. View

Ye Z, Zhang J, Townsend D, Tew K . Oxidative stress, redox regulation and diseases of cellular differentiation. Biochim Biophys Acta. 2014; 1850(8):1607-21. PMC: 4433447. DOI: 10.1016/j.bbagen.2014.11.010. View

Hospers G, Eisenhauer E, De Vries E . The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects. Br J Cancer. 1999; 80(5-6):629-38. PMC: 2362304. DOI: 10.1038/sj.bjc.6690404. View

Lo H, Ali-Osman F . Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance. Curr Opin Pharmacol. 2007; 7(4):367-74. DOI: 10.1016/j.coph.2007.06.009. View

Raza A, Galili N, Smith S, Godwin J, Lancet J, Melchert M . Phase 1 multicenter dose-escalation study of ezatiostat hydrochloride (TLK199 tablets), a novel glutathione analog prodrug, in patients with myelodysplastic syndrome. Blood. 2009; 113(26):6533-40. DOI: 10.1182/blood-2009-01-176032. View

10.

Vasieva O . The many faces of glutathione transferase pi. Curr Mol Med. 2011; 11(2):129-39. DOI: 10.2174/156652411794859278. View

11.

Depeille P, Cuq P, Mary S, Passagne I, Evrard A, Cupissol D . Glutathione S-transferase M1 and multidrug resistance protein 1 act in synergy to protect melanoma cells from vincristine effects. Mol Pharmacol. 2004; 65(4):897-905. DOI: 10.1124/mol.65.4.897. View

12.

Sato K, Tsuchida S, Tamai K . [Anti-cancer drug resistance and glutathione S-transferases]. Gan To Kagaku Ryoho. 1989; 16(3 Pt 2):592-8. View

13.

Kiziltepe T, Hideshima T, Ishitsuka K, Ocio E, Raje N, Catley L . JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. Blood. 2007; 110(2):709-18. PMC: 1924477. DOI: 10.1182/blood-2006-10-052845. View

14.

Simeone A, McMurtry V, Nieves-Alicea R, Saavedra J, Keefer L, Johnson M . TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells. Breast Cancer Res. 2008; 10(3):R44. PMC: 2481491. DOI: 10.1186/bcr2095. View

15.

Laschak M, Spindler K, Schrader A, Hessenauer A, Streicher W, Schrader M . JS-K, a glutathione/glutathione S-transferase-activated nitric oxide releasing prodrug inhibits androgen receptor and WNT-signaling in prostate cancer cells. BMC Cancer. 2012; 12:130. PMC: 3376035. DOI: 10.1186/1471-2407-12-130. View

16.

Townsend D, Findlay V, Tew K . Glutathione S-transferases as regulators of kinase pathways and anticancer drug targets. Methods Enzymol. 2006; 401:287-307. PMC: 6522258. DOI: 10.1016/S0076-6879(05)01019-0. View

17.

Rosen L, Laxa B, Boulos L, Wiggins L, Keck J, Jameson A . Phase 1 study of TLK286 (Telcyta) administered weekly in advanced malignancies. Clin Cancer Res. 2004; 10(11):3689-98. DOI: 10.1158/1078-0432.CCR-03-0687. View

18.

Rotili D, De Luca A, Tarantino D, Pezzola S, Forgione M, Morozzo Della Rocca B . Synthesis and structure--activity relationship of new cytotoxic agents targeting human glutathione-S-transferases. Eur J Med Chem. 2014; 89:156-71. DOI: 10.1016/j.ejmech.2014.10.033. View

19.

Wang Z, Qu K, Huang Z, Xu X, Zhang J, Zhang L . Glutathione S-transferase O2 gene rs157077 polymorphism predicts response to transarterial chemoembolization in hepatocellular carcinoma. Tumour Biol. 2015; 36(8):6463-9. DOI: 10.1007/s13277-015-3336-z. View

20.

Stamenkovic M, Radic T, Stefanovic I, Coric V, Sencanic I, Pljesa-Ercegovac M . Glutathione S-transferase omega-2 polymorphism Asn142Asp modifies the risk of age-related cataract in smokers and subjects exposed to ultraviolet irradiation. Clin Exp Ophthalmol. 2013; 42(3):277-83. DOI: 10.1111/ceo.12180. View