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Current Enzyme Inhibition

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ISSN (Print): 1573-4080
ISSN (Online): 1875-6662

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Research Article

In Vitro Inhibition Effect and Molecular Docking Study of Curcumin, Resveratrol, and Quercetin on Human Erythrocyte Glutathione Transferase

Author(s): Mine Aksoy*, Muhammet Karaman, Pınar Güller, Uğur Güller and Ö. İrfan Küfrevioğlu

Volume 15, Issue 3, 2019

Page: [197 - 205] Pages: 9

DOI: 10.2174/1573408016666191231123544

Price: $65

Abstract

Background: Chemotherapy has shown varying success rates in the treatment of metastatic cancer in the last 50 years. One of the problems in the use of many chemotherapeutic agents is to increase the expression of glutathione transferase enzyme (GST; EC 2.5.1.18). Therefore, the development of GST inhibitors is important to improve the effectiveness of antitumor drugs and to overcome multi-drug resistance.

Introduction: Glutathione S-transferases (GSTs) are a major member of enzymes serving in the detoxification of exogenous and endogenous substances. But, it has been reported that GSTs are overexpressed in many tumour cells, and it has been found to be related to developing resistance to anticancer drugs by these cells. The development of GST inhibitors is important to increase the efficacy of antitumor drugs and overcome multi-drug resistance. The aim of our study was to investigate the effect of natural compounds including curcumin, resveratrol, and quercetin on GST enzyme activity. We also aimed to specify inhibition mechanism of the compounds on human erythrocytes GST (hGST) with in silico study.

Methods: GST was purified from human erythrocytes using affinity chromatography (glutathione agarose). The enzyme purity was checked with SDS-PAGE. After the inhibitory effect of the curcumin, quercetin, resveratrol was investigated. Lastly, inhibition mechanisms of these natural compound were identified with induced-fit docking method.

Results: GST was purified with 19.31% yield from human erythrocytes. In inhibition studies, Ki values of curcumin, quercetin, resveratrol were determined as 0.0021 ± 0.0008, 0.0257 ± 0.0011, 663.3301 ± 0.0936 µM respectively. According to our results, all natural products showed the inhibition effect and the order of inhibition is as follows: curcumin ˃ quercetin ˃ resveratrol.

Conclusion: According to the results of the in vitro and in silico studies, it can be said that curcumin, quercetin, resveratrol are the inhibitors of human erythrocyte GST. In conclusion, these observations may be of great importance for the potential use of these natural compounds as chemopreventive agents.

Keywords: Glutathione S-transferase, in silico study, inhibition, natural products, curcumin, resveratrol.

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[1]
Murray, R. K.; Granner, D. K.; Rodwell, V. W. Harper's illustrated biochemistry (No. 577.1 HAR), 2006. Harper's illustrated biochemistry,
[2]
Sevior, D.K.; Pelkonen, O.; Ahokas, J.T. Hepatocytes: The powerhouse of biotransformation. Int. J. Biochem. Cell Biol., 2012, 44(2), 257-261.
[http://dx.doi.org/10.1016/j.biocel.2011.11.011] [PMID: 22123318]
[3]
Sinnett, D.; Krajinovic, M.; Labuda, D. Genetic susceptibility to childhood acute lymphoblastic leukemia. Leuk. Lymphoma, 2000, 38(5-6), 447-462.
[http://dx.doi.org/10.3109/10428190009059264] [PMID: 10953966]
[4]
Parl, F.F. Glutathione S-transferase genotypes and cancer risk. Cancer Lett., 2005, 221(2), 123-129.
[http://dx.doi.org/10.1016/j.canlet.2004.06.016] [PMID: 15808397]
[5]
Hayeshi, R.; Mutingwende, I.; Mavengere, W.; Masiyanise, V.; Mukanganyama, S. The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin. Food Chem. Toxicol., 2007, 45(2), 286-295.
[http://dx.doi.org/10.1016/j.fct.2006.07.027] [PMID: 17046132]
[6]
Kolobe, D.; Sayed, Y.; Dirr, H.W. Characterization of bromosulphophthalein binding to human glutathione S-transferase A1-1: thermodynamics and inhibition kinetics. Biochem. J., 2004, 382(Pt 2), 703-709.
[http://dx.doi.org/10.1042/BJ20040056] [PMID: 15147239]
[7]
Sheehan, D.; Meade, G.; Foley, V.M.; Dowd, C.A. Structure, function and evolution of glutathione transferases: Implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem. J., 2001, 360(Pt 1), 1-16.
[http://dx.doi.org/10.1042/bj3600001] [PMID: 11695986]
[8]
Che-Mendoza, A.; Penilla, R.P.; Rodrigues, D.A. Insecticide resistance and glutathione S-transferases in mosquitoes: A review. Afr. J. Biotechnol., 2009, 8, 1386-1397.
[9]
McIlwain, C.C.; Townsend, D.M.; Tew, K.D. Glutathione S-transferase polymorphisms: Cancer incidence and therapy. Oncogene, 2006, 25(11), 1639-1648.
[http://dx.doi.org/10.1038/sj.onc.1209373] [PMID: 16550164]
[10]
Lo, H.W.; Ali-Osman, F. Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance. Curr. Opin. Pharmacol., 2007, 7(4), 367-374.
[http://dx.doi.org/10.1016/j.coph.2007.06.009] [PMID: 17681492]
[11]
Balyan, R.; Kudugunti, S.K.; Hamad, H.A.; Yousef, M.S.; Moridani, M.Y. Bioactivation of luteolin by tyrosinase selectively inhibits glutathione S-transferase. Chem. Biol. Interact., 2015, 240, 208-218.
[http://dx.doi.org/10.1016/j.cbi.2015.08.011] [PMID: 26279214]
[12]
Wang, C.H.; Wu, H.T.; Cheng, H.M.; Yen, T.J.; Lu, I.H.; Chang, H.C.; Jao, S.C.; Shing, T.K.M.; Li, W.S. Inhibition of glutathione S-transferase M1 by new gabosine analogues is essential for overcoming cisplatin resistance in lung cancer cells. J. Med. Chem., 2011, 54(24), 8574-8581.
[http://dx.doi.org/10.1021/jm201131n] [PMID: 22085405]
[13]
Mansoori, B.; Mohammadi, A.; Davudian, S.; Shirjang, S.; Baradaran, B. The different mechanisms of cancer drug resistance: A brief review. Adv. Pharm. Bull., 2017, 7(3), 339-348.
[http://dx.doi.org/10.15171/apb.2017.041] [PMID: 29071215]
[14]
Habig, W.H.; Jakoby, W.B. Assays for differentiation of glutathione S-transferases. Methods Enzymol., 1981, 77, 398-405.
[http://dx.doi.org/10.1016/S0076-6879(81)77053-8] [PMID: 7329316]
[15]
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 1976, 72(1-2), 248-254.
[http://dx.doi.org/10.1016/0003-2697(76)90527-3] [PMID: 942051]
[16]
Schrödinger, L. Drug Discovery Suite; New York, NY, 2017.
[17]
Yiğit, B.; Kaya, R.; Taslimi, P.; Işık, Y.; Karaman, M.; Yiğit, M.; Özdemir, İ.; Gulçin, İ. Imidazolinium chloride salts bearing wingtip groups: Synthesis, molecular docking and metabolic enzymes inhibition. J. Mol. Struct., 2018, 1179, 709-718.
[http://dx.doi.org/10.1016/j.molstruc.2018.11.038]
[18]
Bayrak, Ç.; Taslimi, P.; Karaman, H.S.; Gülçin, İ.; Menzek, A. The first synthesis, carbonic anhydrase inhibition and anticholinergic activities of some bromophenol derivatives with S including natural products. Bioorg. Chem., 2019, 85, 128-139.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.012]
[19]
Schrödinger, L. Induced Fit Docking protocol; Glide version 5.5; Prime version 2.1, New York, NY. 2009.
[20]
Gottesman, M.M.; Pastan, I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem., 1993, 62, 385-427.
[http://dx.doi.org/10.1146/annurev.bi.62.070193.002125] [PMID: 8102521]
[21]
Volm, M. Multidrug resistance and its reversal. Anticancer Res., 1998, 18(4C), 2905-2917.
[PMID: 9713485]
[22]
Eaton, D.L.; Bammler, T.K. Concise review of the glutathione S-transferases and their significance to toxicology. Toxicol. Sci., 1999, 49(2), 156-164.
[http://dx.doi.org/10.1093/toxsci/49.2.156] [PMID: 10416260]
[23]
McLellan, L.I.; Wolf, C.R. Glutathione and glutathione-dependent enzymes in cancer drug resistance. Drug Resist. Updat., 1999, 2(3), 153-164.
[http://dx.doi.org/10.1054/drup.1999.0083] [PMID: 11504486]
[24]
Ruzza, P.; Rosato, A.; Rossi, C.R.; Floreani, M.; Quintieri, L. Glutathione transferases as targets for cancer therapy. Anticancer. Agents Med. Chem., 2009, 9(7), 763-777.
[http://dx.doi.org/10.2174/187152009789056895] [PMID: 19538171]
[25]
Hebert, H.; Jegerschöld, C. The structure of membrane associated proteins in eicosanoid and glutathione metabolism as determined by electron crystallography. Curr. Opin. Struct. Biol., 2007, 17(4), 396-404.
[http://dx.doi.org/10.1016/j.sbi.2007.07.008] [PMID: 17870465]
[26]
Awasthi, Y.C.; Sharma, R.; Singhal, S.S. Human glutathione S-transferases. Int. J. Biochem., 1994, 26(3), 295-308.
[http://dx.doi.org/10.1016/0020-711X(94)90050-7] [PMID: 8187927]
[27]
Chandra, R.K.; Bentz, B.G.; Haines, G.K., III; Robinson, A.M.; Radosevich, J.A. Expression of glutathione s-transferase pi in benign mucosa, Barrett’s metaplasia, and adenocarcinoma of the esophagus. Head Neck, 2002, 24(6), 575-581.
[http://dx.doi.org/10.1002/hed.10093] [PMID: 12112555]
[28]
Piipari, R.; Nurminen, T.; Savela, K.; Hirvonen, A.; Mäntylä, T.; Anttila, S. Glutathione S-transferases and aromatic DNA adducts in smokers’ bronchoalveolar macrophages. Lung Cancer, 2003, 39(3), 265-272.
[http://dx.doi.org/10.1016/S0169-5002(02)00510-X] [PMID: 12609564]
[29]
Mannervik, B.; Castro, V.M.; Danielson, U.H.; Tahir, M.K.; Hansson, J.; Ringborg, U. Expression of class Pi glutathione transferase in human malignant melanoma cells. Carcinogenesis, 1987, 8(12), 1929-1932.
[http://dx.doi.org/10.1093/carcin/8.12.1929] [PMID: 3119248]
[30]
Hayes, J.D.; Pulford, D.J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol., 1995, 30(6), 445-600.
[http://dx.doi.org/10.3109/10409239509083491] [PMID: 8770536]
[31]
O’Brien, M.L.; Tew, K.D. Glutathione and related enzymes in multidrug resistance. Eur. J. Cancer, 1996, 32A(6), 967-978.
[http://dx.doi.org/10.1016/0959-8049(96)00051-2] [PMID: 8763337]
[32]
Batist, G.; Tulpule, A.; Sinha, B.K.; Katki, A.G.; Myers, C.E.; Cowan, K.H. Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells. J. Biol. Chem., 1986, 261(33), 15544-15549.
[PMID: 3782078]
[33]
Mahajan, S.; Atkins, W.M. The chemistry and biology of inhibitors and pro-drugs targeted to glutathione S-transferases. Cell. Mol. Life Sci., 2005, 62(11), 1221-1233.
[http://dx.doi.org/10.1007/s00018-005-4524-6] [PMID: 15798895]
[34]
Zhao, G.; Wang, X. Advance in antitumor agents targeting glutathione-S-transferase. Curr. Med. Chem., 2006, 13(12), 1461-1471.
[http://dx.doi.org/10.2174/092986706776872934] [PMID: 16719788]
[35]
Morales, G.A.; Laborde, E. Small-molecule inhibitors of glutathione S-transferase P1-1 as anticancer therapeutic agents. Annu. Rep. Med. Chem., 2007, 42(42), 321-335.
[http://dx.doi.org/10.1016/S0065-7743(07)42020-6]
[36]
van Haaften, R.I.M.; Haenen, G.R.M.M.; van Bladeren, P.J.; Bogaards, J.J.P.; Evelo, C.T.A.; Bast, A. Inhibition of various glutathione S-transferase isoenzymes by RRR-alpha-tocopherol. Toxicol. In Vitro, 2003, 17(3), 245-251.
[http://dx.doi.org/10.1016/S0887-2333(03)00038-9] [PMID: 12781202]
[37]
Appiah-Opong, R.; Commandeur, J.N.M.; Istyastono, E.; Bogaards, J.J.; Vermeulen, N.P.E. Inhibition of human glutathione S-transferases by curcumin and analogues. Xenobiotica, 2009, 39(4), 302-311.
[http://dx.doi.org/10.1080/00498250802702316] [PMID: 19350453]
[38]
Hayeshi, R.; Mukanganyama, S.; Hazra, B.; Abegaz, B.; Hasler, J. The interaction of selected natural products with human recombinant glutathione transferases. Phytother. Res., 2004, 18(11), 877-883.
[http://dx.doi.org/10.1002/ptr.1481] [PMID: 15597303]
[39]
Aksoy, M.; Küfrevioglu, I. Inhibition of human erythrocyte glutathione S-transferase by some flavonoid derivatives. Toxin Rev., 2018, 37(3), 251-257.
[http://dx.doi.org/10.1080/15569543.2017.1345945]
[40]
Abel, E.L.; Lyon, R.P.; Bammler, T.K.C.; Verlinde, C.L.; Lau, S.S.; Monks, T.J.; Eaton, D.L. Estradiol metabolites as isoform-specific inhibitors of human glutathione S-transferases. Chem. Biol. Interact., 2004, 151(1), 21-32.
[http://dx.doi.org/10.1016/j.cbi.2004.10.006] [PMID: 15607759]

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