CoChat
Sign Up
Cited by 625Glutathione Transferases and PolymorphismsPharmacogenetics and Drug MetabolismGenomics, phytochemicals, and oxidative stress

Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases

Open access
Allocati, Nerino, Masulli, Michele, Di Ilio, Carmine, Federici, Luca·2018·Oncogenesis
DOI 10.1038/s41389-017-0025-3PMC PMC5833873
Open this paper in CoChat — free accountOpen PDF

Abstract

Glutathione transferase classical GSH conjugation activity plays a critical role in cellular detoxification against xenobiotics and noxious compounds as well as against oxidative stress. However, this feature is also exploited by cancer cells to acquire drug resistance and improve their survival. As a result, various members of the family were found overexpressed in a number of different cancers. Moreover several GST polymorphisms, ranging from null phenotypes to point mutations, were detected in members of the family and found to correlate with the onset of neuro-degenerative diseases. In the last decades, a great deal of research aimed at clarifying the role played by GSTs in drug resistance, at developing inhibitors to counteract this activity but also at exploiting GSTs for prodrugs specific activation in cancer cells. Here we summarize some of the most important achievements reached in this lively area of research.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41389-017-0025-3

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Ethacrynic acid is a loop diuretic that inhibits GSTM-subfamily proteins, in part by acting as an alternative substrate for glutathione conjugation.

    “Ethacrynic acid is a loop diuretic that inhibits GSTM-subfamily proteins, in part by acting as an alternative substrate for glutathione conjugation (47, 48).”

    From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [48]

    The “Ethacrynic acid and analogues” section describes ethacrynic acid as a diuretic and a substrate/inhibitor of several GSTs; its Fig. 5 caption shows GST-catalyzed conjugation of ethacrynic acid. The copy does not identify it as a loop diuretic or specify GSTM-subfamily inhibition, instead naming GSTP1-1 as an inhibitory target. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 124

  1. [1]Hayes JD Flanagan JU Jowsey IR Glutathione transferases Annu. Rev. Pharmacol. Toxicol. 2005 45 51 88 10.1146/annurev.pharmtox.45.120403.095857 15822171 · DOI
  2. [2]Sheehan D Meade G Foley VM Dowd CA Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily Biochem. J. 2001 360 1 16 10.1042/bj3600001 11695986 PMC1222196 · DOI
  3. [3]Allocati N Federici L Masulli M Di Ilio C Glutathione transferases in bacteria FEBS J. 2009 276 58 75 10.1111/j.1742-4658.2008.06743.x 19016852 · DOI
  4. [4]Allocati N Federici L Masulli M Di Ilio C Distribution of glutathione transferases in Gram-positive bacteria and Archaea Biochimie 2012 94 588 596 10.1016/j.biochi.2011.09.008 21945597 · DOI
  5. [5]Wu B Dong D Human cytosolic glutathione transferases: structure, function, and drug discovery Trends Pharmacol. Sci. 2012 33 656 668 10.1016/j.tips.2012.09.007 23121834 · DOI
  6. [6]Oakley A Glutathione transferases: a structural perspective Drug. Metab. Rev. 2011 43 138 151 10.3109/03602532.2011.558093 21428697 · DOI
  7. [7]Morel F Aninat C The glutathione transferase kappa family Drug. Metab. Rev. 2011 43 281 291 10.3109/03602532.2011.556122 21428694 · DOI
  8. [8]Morgenstern R Zhang J Johansson K Microsomal glutathione transferase 1: mechanism and functional roles Drug. Metab. Rev. 2011 43 300 306 10.3109/03602532.2011.558511 21495795 · DOI
  9. [9]Li YS Hung SC Wei YH Tarng DC GST M1 polymorphism associates with DNA oxidative damage and mortality among hemodialysis patients J. Am. Soc. Nephrol. 2009 20 405 415 10.1681/ASN.2008020227 19056870 PMC2637044 · DOI
  10. [10]Hayes JD Regulation of rat glutathione S-transferase A5 by cancer chemopreventive agents: mechanisms of inducible resistance to aflatoxin B1 Chem. Biol. Interact. 1998 111-112 51 67 10.1016/S0009-2797(97)00151-8 9679543 · DOI
  11. [11]Wild CP Turner PC The toxicology of aflatoxins as a basis for public health decisions Mutagenesis 2002 17 471 481 10.1093/mutage/17.6.471 12435844 · DOI
  12. [12]Dohnal V Wu Q Kuca K Metabolism of aflatoxins: key enzymes and interindividual as well as interspecies differences Arch. Toxicol. 2014 88 1635 1644 10.1007/s00204-014-1312-9 25027283 · DOI
  13. [13]Singhal SS Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling Toxicol. Appl. Pharmacol. 2015 289 361 370 10.1016/j.taap.2015.10.006 26476300 PMC4852854 · DOI
  14. [14]Minko IG Chemistry and biology of DNA containing 1,N(2)-deoxyguanosine adducts of the alpha,beta-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxynonenal Chem. Res. Toxicol. 2009 22 759 778 10.1021/tx9000489 19397281 PMC2685875 · DOI
  15. [15]Dalleau S Baradat M Gueraud F Huc L Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance Cell. Death Differ. 2013 20 1615 1630 10.1038/cdd.2013.138 24096871 PMC3824598 · DOI · Paper page
  16. [16]Yang Y Huycke MM Herman TS Wang X Glutathione S-transferase alpha 4 induction by activator protein 1 in colorectal cancer Oncogene 2016 35 5795 5806 10.1038/onc.2016.113 27065323 PMC9619338 · DOI
  17. [17]Vatsyayan R Lelsani PC Awasthi S Singhal SS RLIP76: a versatile transporter and an emerging target for cancer therapy Biochem. Pharmacol. 2010 79 1699 1705 10.1016/j.bcp.2010.01.016 20097178 PMC2874070 · DOI
  18. [18]Faroon O Acrolein health effects Toxicol. Ind. Health 2008 24 447 490 10.1177/0748233708094188 19028774 · DOI
  19. [19]Henning RJ Johnson GT Coyle JP Harbison RD Acrolein can cause cardiovascular disease: a review Cardiovasc. Toxicol. 2017 17 227 236 10.1007/s12012-016-9396-5 28084565 · DOI
  20. [20]Stevens JF Maier CS Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease Mol. Nutr. Food Res. 2008 52 7 25 10.1002/mnfr.200700412 18203133 PMC2423340 · DOI
  21. [21]Deponte M Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes Biochim. Biophys. Acta 2013 1830 3217 3266 10.1016/j.bbagen.2012.09.018 23036594 · DOI
  22. [22]Pettersson PL Thoren S Jakobsson PJ Human microsomal prostaglandin E synthase 1: a member of the MAPEG protein superfamily Methods Enzymol. 2005 401 147 161 10.1016/S0076-6879(05)01009-8 16399384 · DOI
  23. [23]Psarra A Nikolaou A Kokotou MG Limnios D Kokotos G Microsomal prostaglandin E2 synthase-1 inhibitors: a patent review Expert. Opin. Ther. Pat. 2017 27 1047 1059 10.1080/13543776.2017.1344218 28627961 · DOI
  24. [24]Singh S Cytoprotective and regulatory functions of glutathione S-transferases in cancer cell proliferation and cell death Cancer Chemother. Pharmacol. 2015 75 1 15 10.1007/s00280-014-2566-x 25143300 · DOI
  25. [25]Laborde E Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death Cell. Death Differ. 2010 17 1373 1380 10.1038/cdd.2010.80 20596078 · DOI
  26. [26]Adler V Regulation of JNK signaling by GSTp EMBO J. 1999 18 1321 1334 10.1093/emboj/18.5.1321 10064598 PMC1171222 · DOI
  27. [27]Karin M Gallagher E From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance IUBMB Life 2005 57 283 295 10.1080/15216540500097111 16036612 · DOI
  28. [28]Bernardini S Role of GST P1-1 in mediating the effect of etoposide on human neuroblastoma cell line Sh-Sy5y J. Cell. Biochem. 2002 86 340 347 10.1002/jcb.10219 12112003 · DOI
  29. [29]Wu Y Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2-ASK1 signals Oncogene 2006 25 5787 5800 10.1038/sj.onc.1209576 16636664 · DOI
  30. [30]De Luca A The fine-tuning of TRAF2-GSTP1-1 interaction: effect of ligand binding and in situ detection of the complex Cell. Death Dis. 2014 5 e1015 10.1038/cddis.2013.529 24457959 PMC4040697 · DOI
  31. [31]Wormhoudt LW Commandeur JN Vermeulen NP Genetic polymorphisms of human N-acetyltransferase, cytochrome P450, glutathione-S-transferase, and epoxide hydrolase enzymes: relevance to xenobiotic metabolism and toxicity Crit. Rev. Toxicol. 1999 29 59 124 10.1080/10408449991349186 10066160 · DOI
  32. [32]Di Pietro G Magno LA Rios-Santos F Glutathione S-transferases: an overview in cancer research Expert. Opin. Drug. Metab. Toxicol. 2010 6 153 170 10.1517/17425250903427980 20078251 · DOI
  33. [33]Board PG Menon D Glutathione transferases, regulators of cellular metabolism and physiology Biochim. Biophys. Acta 2013 1830 3267 3288 10.1016/j.bbagen.2012.11.019 23201197 · DOI
  34. [34]Townsend D Tew K Cancer drugs, genetic variation and the glutathione-S-transferase gene family Am. J. Pharmacol. 2003 3 157 172 10.2165/00129785-200303030-00002 PMC9086716 12814324 · DOI
  35. [35]Mostafavi SS Impact of null genotypes of GSTT1 and GSTM1 with uterine leiomyoma risk in Iranian population J. Obstet. Gynaecol. Res. 2016 42 434 439 10.1111/jog.12924 26785830 · DOI
  36. [36]Eslami S Sahebkar A Glutathione-S-transferase M1 and T1 null genotypes are associated with hypertension risk: a systematic review and meta-analysis of 12 studies Curr. Hypertens. Rep. 2014 16 432 10.1007/s11906-014-0432-1 24788870 · DOI
  37. [37]He P Wei M Wang Y Liu Q Associations among glutathione S-transferase T1, M1, and P1 polymorphisms and the risk of oral leukoplakia Genet. Test. Mol. Biomark. 2016 20 312 321 10.1089/gtmb.2015.0308 27152506 · DOI
  38. [38]Geng P Genetic contribution of polymorphisms in glutathione S-transferases to brain tumor risk Mol. Neurobiol. 2016 53 1730 1740 10.1007/s12035-015-9097-2 25735248 · DOI
  39. [39]Weich N GSTM1 and GSTP1, but not GSTT1 genetic polymorphisms are associated with chronic myeloid leukemia risk and treatment response Cancer Epidemiol. 2016 44 16 21 10.1016/j.canep.2016.07.008 27454607 · DOI
  40. [40]Campos, C. Z. et al. Glutathione S-transferases deletions may act as prognosis and therapeutic markers in breast cancer. Clin. Exp. Med. 2017. 28455582
  41. [41]Malik SS Genetic polymorphism of GSTM1 and GSTT1 and risk of prostatic carcinoma - a meta-analysis of 7,281 prostate cancer cases and 9,082 healthy controls Asian Pac. J. Cancer Prev. 2016 17 2629 2635 10.7314/APJCP.2016.17.4.2301 27268642 · DOI
  42. [42]Xu YT Genetic polymorphisms in Glutathione S-transferase Omega (GSTO) and cancer risk: a meta-analysis of 20 studies Sci. Rep. 2014 4 6578 10.1038/srep06578 25300926 PMC4192632 · DOI
  43. [43]Song Y Glutathione S-transferase T1 (GSTT1) null polymorphism, smoking, and their interaction in coronary heart disease: a comprehensive meta-analysis Heart Lung. Circ. 2017 26 362 370 10.1016/j.hlc.2016.07.005 27686690 · DOI
  44. [44]Hruska P Combinations of common polymorphisms within GSTA1 and GSTT1 as a risk factor for psoriasis in a Central European population: a case-control study J. Eur. Acad. Dermatol. Venereol. 2017 31 e461 e463 10.1111/jdv.14266 28401601 · DOI
  45. [45]Shiota M Gene polymorphisms in antioxidant enzymes correlate with the efficacy of androgen-deprivation therapy for prostate cancer with implications of oxidative stress Ann. Oncol. 2017 28 569 575 27993795
  46. [46]Board PG Menon D Structure, function and disease relevance of Omega-class glutathione transferases Arch. Toxicol. 2016 90 1049 1067 10.1007/s00204-016-1691-1 26993125 · DOI
  47. [47]Kumar A Role of glutathione-S-transferases in neurological problems Expert. Opin. Ther. Pat. 2017 27 299 309 10.1080/13543776.2017.1254192 27785931 · DOI
  48. [48]Johnson W Wilson-Delfosse AL Mieyal JJ Dysregulation of glutathione homeostasis in neurodegenerative diseases Nutrients 2012 4 1399 1440 10.3390/nu4101399 23201762 PMC3497002 · DOI
  49. [49]Uttara B Singh AV Zamboni P Mahajan RT Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options Curr. Neuropharmacol. 2009 7 65 74 10.2174/157015909787602823 19721819 PMC2724665 · DOI · Paper page
  50. [50]Mazzetti AP Fiorile MC Primavera A Lo Bello M Glutathione transferases and neurodegenerative diseases Neurochem. Int. 2015 82 10 18 10.1016/j.neuint.2015.01.008 25661512 · DOI
  51. [51]Lovell MA Xie C Markesbery WR Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer’s disease Neurology 1998 51 1562 1566 10.1212/WNL.51.6.1562 9855502 · DOI
  52. [52]Bernardini S Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele Clin. Chem. 2005 51 944 951 10.1373/clinchem.2004.045955 15805147 · DOI
  53. [53]Piacentini S GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer’s disease: association hypothesis for an uncommon genetic variant Neurosci. Lett. 2012 506 203 207 10.1016/j.neulet.2011.11.005 22100662 · DOI
  54. [55]Dauer W Przedborski S Parkinson’s disease: mechanisms and models Neuron 2003 39 889 909 10.1016/S0896-6273(03)00568-3 12971891 · DOI · Paper page
  55. [56]Shi M Identification of glutathione S-transferase pi as a protein involved in Parkinson disease progression Am. J. Pathol. 2009 175 54 65 10.2353/ajpath.2009.081019 19498008 PMC2708794 · DOI
  56. [57]Castro-Caldas M Glutathione S-transferase pi mediates MPTP-induced c-Jun N-terminal kinase activation in the nigrostriatal pathway Mol. Neurobiol. 2012 45 466 477 10.1007/s12035-012-8266-9 22539231 · DOI
  57. [58]Laliberte RE Glutathione s-transferase omega 1-1 is a target of cytokine release inhibitory drugs and may be responsible for their effect on interleukin-1beta posttranslational processing J. Biol. Chem. 2003 278 16567 16578 10.1074/jbc.M211596200 12624100 · DOI
  58. [59]Fisher RS ILAE official report: a practical clinical definition of epilepsy Epilepsia 2014 55 475 482 10.1111/epi.12550 24730690 · DOI · Paper page
  59. [60]Ercegovac M GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case-control study Seizure 2015 32 30 36 10.1016/j.seizure.2015.08.010 26552558 · DOI
  60. [61]Chbili C Effects of glutathione S-transferase M1 and T1 deletions on epilepsy risk among a Tunisian population Epilepsy Res. 2014 108 1168 1173 10.1016/j.eplepsyres.2014.05.009 24970787 · DOI
  61. [62]Shang W Expressions of glutathione S-transferase alpha, mu, and pi in brains of medically intractable epileptic patients BMC Neurosci. 2008 9 67 10.1186/1471-2202-9-67 18644106 PMC2490696 · DOI
  62. [63]Sun YM Lu C Wu ZY Spinocerebellar ataxia: relationship between phenotype and genotype – a review Clin. Genet. 2016 90 305 314 10.1111/cge.12808 27220866 · DOI
  63. [64]Almaguer-Gotay D Role of glutathione S-transferases in the spinocerebellar ataxia type 2 clinical phenotype J. Neurol. Sci. 2014 341 41 45 10.1016/j.jns.2014.03.045 24780439 · DOI
  64. [65]Almaguer-Mederos LE Association of glutathione S-transferase omega polymorphism and spinocerebellar ataxia type 2 J. Neurol. Sci. 2017 372 324 328 10.1016/j.jns.2016.11.075 28017238 · DOI
  65. [66]Eum KD Modification of the association between lead exposure and amyotrophic lateral sclerosis by iron and oxidative stress related gene polymorphisms Amyotroph. Lateral Scler. Front. Degener. 2015 16 72 79 10.3109/21678421.2014.964259 PMC4467726 25293352 · DOI
  66. [67]van de Giessen E Association study on glutathione S-transferase omega 1 and 2 and familial ALS Amyotroph. Lateral Scler. 2008 9 81 84 10.1080/17482960701702553 18427999 · DOI
  67. [68]Sau A Pellizzari Tregno F Valentino F Federici G Caccuri AM Glutathione transferases and development of new principles to overcome drug resistance Arch. Biochem. Biophys. 2010 500 116 122 10.1016/j.abb.2010.05.012 20494652 · DOI
  68. [69]Gate L Tew KD Glutathione S-transferases as emerging therapeutic targets Expert. Opin. Ther. Targets 2001 5 477 489 10.1517/14728222.5.4.477 12540261 · DOI
  69. [70]Meijerman I Beijnen JH Schellens JH Combined action and regulation of phase II enzymes and multidrug resistance proteins in multidrug resistance in cancer Cancer Treat. Rev. 2008 34 505 520 10.1016/j.ctrv.2008.03.002 18413281 · DOI
  70. [71]Homolya L Varadi A Sarkadi B Multidrug resistance-associated proteins: Export pumps for conjugates with glutathione, glucuronate or sulfate Biofactors 2003 17 103 114 10.1002/biof.5520170111 12897433 · DOI
  71. [72]Keppler D Export pumps for glutathione S-conjugates Free. Radic. Biol. Med. 1999 27 985 991 10.1016/S0891-5849(99)00171-9 10569630 · DOI
  72. [73]Johnstone TC Suntharalingam K Lippard SJ The next generation of platinum drugs: targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs Chem. Rev. 2016 116 3436 3486 10.1021/acs.chemrev.5b00597 26865551 PMC4792284 · DOI
  73. [74]Ho GY Woodward N Coward JI Cisplatin versus carboplatin: comparative review of therapeutic management in solid malignancies Crit. Rev. Oncol. Hematol. 2016 102 37 46 10.1016/j.critrevonc.2016.03.014 27105947 · DOI
  74. [75]Rathinam, R., Ghosh, S., Neumann, W. L., & Jamesdaniel, S. Cisplatin-induced apoptosis in auditory, renal, and neuronal cells is associated with nitration and downregulation of LMO4. Cell Death Discov. 1 (2015). https://doi.org/10.1038/cddiscovery.2015.52 PMC4765951 26925255 · DOI
  75. [77]Pasello M Overcoming glutathione S-transferase P1-related cisplatin resistance in osteosarcoma Cancer Res. 2008 68 6661 6668 10.1158/0008-5472.CAN-07-5840 18701490 · DOI
  76. [78]Bouligand J Induction of glutathione synthesis explains pharmacodynamics of high-dose busulfan in mice and highlights putative mechanisms of drug interaction Drug. Metab. Dispos. 2007 35 306 314 10.1124/dmd.106.012880 17132762 · DOI
  77. [79]Gibbs JP Czerwinski M Slattery JT Busulfan-glutathione conjugation catalyzed by human liver cytosolic glutathione S-transferases Cancer Res. 1996 56 3678 3681 8706007
  78. [80]Czerwinski M Gibbs JP Slattery JT Busulfan conjugation by glutathione S-transferases alpha, mu, and pi Drug. Metab. Dispos. 1996 24 1015 1019 8886613
  79. [81]Scian M Atkins WM The busulfan metabolite EdAG irreversibly glutathionylates glutaredoxins Arch. Biochem. Biophys. 2015 583 96 104 10.1016/j.abb.2015.08.005 26278353 PMC4575911 · DOI
  80. [82]Kankotia S Stacpoole PW Dichloroacetate and cancer: new home for an orphan drug? Biochim. Biophys. Acta 2014 1846 617 629 25157892
  81. [83]Polekhina G Board PG Blackburn AC Parker MW Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity Biochemistry 2001 40 1567 1576 10.1021/bi002249z 11327815 · DOI
  82. [84]Jahn SC GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate Biochim. Biophys. Acta 2016 1860 1202 1210 10.1016/j.bbagen.2016.01.024 26850694 PMC4837035 · DOI
  83. [85]James MO Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1 Pharmacol. Ther. 2016 170 166 180 10.1016/j.pharmthera.2016.10.018 27771434 PMC5274567 · DOI
  84. [86]Mahajan S Atkins WM The chemistry and biology of inhibitors and pro-drugs targeted to glutathione S-transferases Cell. Mol. Life Sci. 2005 62 1221 1233 10.1007/s00018-005-4524-6 15798895 PMC11139158 · DOI
  85. [87]Wu JH Batist G Glutathione and glutathione analogues; therapeutic potentials Biochim. Biophys. Acta 2013 1830 3350 3353 10.1016/j.bbagen.2012.11.016 23201199 · DOI
  86. [88]Harshbarger W Structural and biochemical analyses reveal the mechanism of glutathione S-transferase Pi 1 inhibition by the anti-cancer compound piperlongumine J. Biol. Chem. 2017 292 112 120 10.1074/jbc.M116.750299 27872191 PMC5217671 · DOI
  87. [89]Townsend DM Tew KD The role of glutathione-S-transferase in anti-cancer drug resistance Oncogene 2003 22 7369 7375 10.1038/sj.onc.1206940 14576844 PMC6361125 · DOI · Paper page
  88. [90]Punganuru SR Mostofa AG Madala HR Basak D Srivenugopal KS Potent anti-proliferative actions of a non-diuretic glucosamine derivative of ethacrynic acid Bioorg. Med. Chem. Lett. 2016 26 2829 2833 10.1016/j.bmcl.2016.04.062 27156773 · DOI
  89. [91]Mignani S A novel class of ethacrynic acid derivatives as promising drug-like potent generation of anticancer agents with established mechanism of action Eur. J. Med. Chem. 2016 122 656 673 10.1016/j.ejmech.2016.05.063 27448922 · DOI
  90. [92]Ang WH Synthesis and characterization of platinum(IV) anticancer drugs with functionalized aromatic carboxylate ligands: influence of the ligands on drug efficacies and uptake J. Med. Chem. 2005 48 8060 8069 10.1021/jm0506468 16335930 · DOI
  91. [93]Parker LJ Studies of glutathione transferase P1-1 bound to a platinum(IV)-based anticancer compound reveal the molecular basis of its activation Chem. Eur. J. 2011 17 7806 7816 10.1002/chem.201100586 21681839 · DOI
  92. [94]Johansson K Characterization of new potential anticancer drugs designed to overcome glutathione transferase mediated resistance Mol. Pharmacol. 2011 8 1698 1708 10.1021/mp2000692 21851097 · DOI
  93. [95]Li S Overcoming resistance to cisplatin by inhibition of glutathione S-transferases (GSTs) with ethacraplatin micelles in vitro and in vivo Biomaterials 2017 144 119 129 10.1016/j.biomaterials.2017.08.021 28834763 · DOI
  94. [96]Tentori L The glutathione transferase inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) increases temozolomide efficacy against malignant melanoma Eur. J. Cancer 2011 47 1219 1230 10.1016/j.ejca.2010.12.008 21269821 · DOI
  95. [97]Graziani G A new water soluble MAPK activator exerts antitumor activity in melanoma cells resistant to the BRAF inhibitor vemurafenib Biochem. Pharmacol. 2015 95 16 27 10.1016/j.bcp.2015.03.004 25795251 · DOI
  96. [98]Federici L Structural basis for the binding of the anticancer compound 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol to human glutathione s-transferases Cancer Res. 2009 69 8025 8034 10.1158/0008-5472.CAN-09-1314 19808963 · DOI
  97. [99]Sau A Targeting GSTP1-1 induces JNK activation and leads to apoptosis in cisplatin-sensitive and -resistant human osteosarcoma cell lines Mol. Biosyst. 2012 8 994 1006 10.1039/C1MB05295K 22068640 · DOI
  98. [100]De Luca A A novel orally active water-soluble inhibitor of human glutathione transferase exerts a potent and selective antitumor activity against human melanoma xenografts Oncotarget 2015 6 4126 4143 25595904 PMC4414177
  99. [101]Luisi G Nitrobenzoxadiazole-based GSTP1-1 inhibitors containing the full peptidyl moiety of (pseudo)glutathione J. Enzym. Inhib. Med. Chem. 2016 31 924 930 10.3109/14756366.2015.1070845 26329912 · DOI
  100. [102]De Luca A The nitrobenzoxadiazole derivative MC3181 blocks melanoma invasion and metastasis Oncotarget 2017 8 15520 15538 28107182 PMC5362503
  101. [103]De Luca A Hartinger CG Dyson PJ Lo Bello M Casini A A new target for gold(I) compounds: glutathione-S-transferase inhibition by auranofin J. Inorg. Biochem. 2013 119 38 42 10.1016/j.jinorgbio.2012.08.006 23183361 · DOI
  102. [105]Lucente G Luisi G Pinnen F Design and synthesis of glutathione analogues Il Farm. 1998 53 721 735 10.1016/S0014-827X(98)00098-6 10230053 · DOI
  103. [106]Mahadevan D Sutton GR Ezatiostat hydrochloride for the treatment of myelodysplastic syndromes Expert. Opin. Investig. Drugs 2015 24 725 733 10.1517/13543784.2015.1021003 25724698 · DOI
  104. [107]Bezerra DP Overview of the therapeutic potential of piplartine (piperlongumine) Eur. J. Pharm. Sci. 2013 48 453 463 10.1016/j.ejps.2012.12.003 23238172 · DOI
  105. [108]Ruzza P Calderan A Glutathione transferase (GST)-activated prodrugs Pharmaceutics 2013 5 220 231 10.3390/pharmaceutics5020220 24300447 PMC3834953 · DOI
  106. [109]Ramsay EE Dilda PJ Glutathione S-conjugates as prodrugs to target drug-resistant tumors Front. Pharmacol. 2014 5 181 10.3389/fphar.2014.00181 25157234 PMC4127970 · DOI
  107. [110]Dourado DF Fernandes PA Ramos MJ Mannervik B Mechanism of glutathione transferase P1-1-catalyzed activation of the prodrug canfosfamide (TLK286, TELCYTA) Biochemistry 2013 52 8069 8078 10.1021/bi4005705 24066958 · DOI
  108. [111]Tew KD TLK-286: a novel glutathione S-transferase-activated prodrug Expert. Opin. Invest. Drugs 2005 14 1047 1054 10.1517/13543784.14.8.1047 16050796 · DOI
  109. [112]Vergote I Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer Int. J. Gynecol. Cancer 2010 20 772 780 10.1111/IGC.0b013e3181daaf59 20973267 · DOI
  110. [113]Kavanagh JJ Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer J. Hematol. Oncol. 2010 3 9 10.1186/1756-8722-3-9 20222977 PMC2851575 · DOI
  111. [114]Sequist LV Phase 1-2a multicenter dose-ranging study of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy for patients with advanced non-small cell lung cancer J. Thorac. Oncol. 2009 4 1389 1396 10.1097/JTO.0b013e3181b6b84b 19701107 · DOI
  112. [116]Ikhlas S Ahmad M Metformin: Insights into its anticancer potential with special reference to AMPK dependent and independent pathways Life Sci. 2017 185 53 62 10.1016/j.lfs.2017.07.029 28755883 · DOI
  113. [117]Morales DR Morris AD Metformin in cancer treatment and prevention Annu. Rev. Med. 2015 66 17 29 10.1146/annurev-med-062613-093128 25386929 · DOI
  114. [118]Whitburn J Edwards CM Sooriakumaran P Metformin and prostate cancer: a new role for an old drug Curr. Urol. Rep. 2017 18 46 10.1007/s11934-017-0693-8 28444639 PMC5405102 · DOI
  115. [119]Zhou XL Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: a meta-analysis of cohort studies Oncotarget 2017 8 55622 55631 28903449 PMC5589688
  116. [120]Rautio J Vernerova M Aufderhaar I Huttunen KM Glutathione-S-transferase selective release of metformin from its sulfonamide prodrug Bioorg. Med. Chem. Lett. 2014 24 5034 5036 10.1016/j.bmcl.2014.09.019 25248681 · DOI
  117. [121]Huttunen KM The first bioreversible prodrug of metformin with improved lipophilicity and enhanced intestinal absorption J. Med. Chem. 2009 52 4142 4148 10.1021/jm900274q 19522462 · DOI
  118. [122]Xu W Liu LZ Loizidou M Ahmed M Charles IG The role of nitric oxide in cancer Cell. Res. 2002 12 311 320 10.1038/sj.cr.7290133 12528889 · DOI
  119. [123]Shami PJ JS-K, a glutathione/glutathione S-transferase-activated nitric oxide donor of the diazeniumdiolate class with potent antineoplastic activity Mol. Cancer Ther. 2003 2 409 417 12700285
  120. [124]Findlay VJ Tumor cell responses to a novel glutathione S-transferase-activated nitric oxide-releasing prodrug Mol. Pharmacol. 2004 65 1070 1079 10.1124/mol.65.5.1070 15102935 PMC9012296 · DOI
  121. [125]Chakrapani H Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs Bioorg. Med. Chem. 2008 16 9764 9771 10.1016/j.bmc.2008.09.063 18930407 PMC2631660 · DOI
  122. [126]Xue R Design, synthesis, and evaluation of diazeniumdiolate-based DNA cross-linking agents activatable by glutathione S-transferase Org. Lett. 2016 18 5196 5199 10.1021/acs.orglett.6b02222 27696880 · DOI
  123. [127]Genovese I Ilari A Assaraf YG Fazi F Colotti G Not only P-glycoprotein: amplification of the ABCB1-containing chromosome region 7q21 confers multidrug resistance upon cancer cells by coordinated overexpression of an assortment of resistance-related proteins Drug. Resist. Update 2017 32 23 46 10.1016/j.drup.2017.10.003 29145976 · DOI · Paper page
  124. [128]van Gisbergen MW Chemical reactivity window determines prodrug efficiency toward glutathione transferase overexpressing cancer cells Mol. Pharmacol. 2016 13 2010 2025 10.1021/acs.molpharmaceut.6b00140 PMC5241094 27093577 · DOI

Cited by

Sorted by citations

Authors
Allocati, N., Masulli, M., Di Ilio, C., & Federici, L.
Affiliations
University of Chieti-Pescara (IT)
Corresponding author
Allocati, Nerino
ORCID
Venue
Oncogenesis
Publisher
Springer Science and Business Media LLC
Published
2018-01-24
Volume
7
Issue
1
Pages
8-8
ISSN
2157-9024 (ISSN-L)
DOI
10.1038/s41389-017-0025-3
PMC
PMC5833873
OpenAlex
W2791136219
Cited by
625
References
4
Citations by year
2026: 63 · 2025: 69 · 2024: 95 · 2023: 65 · 2022: 83 · 2021: 97 · 2020: 74 · 2019: 59 · 2018: 20
FWCI
6.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Oncogenesis (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Associazione Italiana per la Ricerca sul Cancro (IG2014-15197, IG-2014)
  • Università degli Studi G. d'Annunzio Chieti - Pescara
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords
glutathione S-transferase, GST inhibitors, prodrugs, drug resistance, cancer, neurodegenerative diseases, GST polymorphisms, xenobiotic detoxification, oxidative stress, GSH conjugation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review