Inhibition of soluble glutathione S-transferase by diuretic drugs

Ahokas, Jorma T.; Davies, C.; Ravenscroft, Peter J.; Emmerson, B. T.

doi:10.1016/0006-2952(84)90549-5

Cited by 51 publications

(13 citation statements)

References 4 publications

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“…Kinetic analyses done in vitro (4)(5)(6)(7)(8)(9)(10)(11) were predictive of the ability of GST to confer resistance to alkylating agents; specifically, as we demonstrated, of the three GST classes, GST ir and Ya (acidic and basic classes ofGST) would confer the greatest resistance to anti-BPDE (10, 11) and chlorambucil (4-6), respectively. In support of the findings that GST Proc.…”

Section: Resultsmentioning

confidence: 99%

“…In one mechanism, GSTs catalyze the covalent addition of the tripeptide glutathione to electrophilic molecules, including products of the cytochrome P-450 mixed-function oxidases, yielding conjugates that are generally less reactive and more readily excreted (1). As demonstrated with in vitro kinetic analyses, GSTs can catalyze the conjugation of glutathione to the anticancer drugs melphalan (4)(5)(6), chlorambucil (4), cyclophosphamide (4), 1,3-bis(2-chloroethyl)-l-nitrosourea (7), and mitoxantrone (8); the diuretic drug ethacrynic acid (9); and the activated metabolite (anti-BPDE, a racemic mixture of 7/,8a-dihydroxy-9a,10a-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and 7a,8f3-dihydroxy-9,3,108-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) of the environmental pollutant benzo[a]pyrene (10,11). Additionally, GSTs can sequester hydrophobic compounds by noncovalent and covalent binding (2), and by their intrinsic peroxidase activity, some GSTs can detoxify lipid and DNA hydroperoxides (12).…”

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Expression of recombinant glutathione S-transferase pi, Ya, or Yb1 confers resistance to alkylating agents.

Puchalski

Fahl²

1990

Proc. Natl. Acad. Sci. U.S.A.

129

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Increased levels of glutathione S-transferase (GST; RX:glutathione R-transferase; EC 2.5.1.18) mRNA, protein, and activity in tumor biopsy samples and in drugresistant cultured cells are associated with resistance to anticancer drugs. We report that each of three full-length cloned GST cDNAs, that for X7 (acidic), Ya (basic), and Yb1 (neutral), can confer drug resistance when expressed in cultured mammalian cells. In one approach, stably transfected mouse C3H/10T½ cells that express GST ar, Ya, or Ybj were cloned and analyzed for drug resistance in colony-forming assays. Transiently transfected COS cells that were sorted on a fluorescence-activated cell sorter were used in the second approach to avoid interclonal variation in factors other than the recombinant GST and to show that reversion of transient GST expression correlated with loss of drug resistance. A sorting technique, developed to separate the 20% of the electroporated COS cell population that transiently expressed GST ir, Ya, or Yb, from the nonexpressing population, was based on a GST-catalyzed intracellular cotijugation of glutathione to the fluorescent labeling reagent monochlorobimane. GST Ya conferred the greatest increase in resistance to chlorambucil and melphalan (1.3-to 2.9-fold), Yb, conferred the greatest increase in resistance to cisplatin (1.5-fold), and ir conferred the greatest increase in resistance to a racemic mixture of 7fi,8a-dihydroxy-9a, 10ar-epoxy-7,8,9,10-tetrahydrobenzo[alpyrene and 7a,8p-dihydroxy-9fi,108-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and doxorubicin (1.5-and 1.3-fold) relative to controls. These resistance values to alkylating agents are commensurate with values observed clinically. Cytotoxicity curves representing recombinant GST' populations were significantly different from their controls with P values ranging from 0.005 to 0.0001. No resistance to vinblastine was detected. Conferred drug resistance was proportional to the magnitude of GST Ya expression, and reversion of transient expression in GST Ya+ COS cell clones to a GST Ya-phenotype was associated with total loss of drug resistance.A major obstacle to the effective treatment of cancer is the inability to eliminate tumor cell subpopulations that have an intrinsic or acquired resistance to anticancer drugs. Various cellular defense mechanisms have developed that may be important in conferring protection against cytotoxicity induced by anticancer drugs. Decreased intracellular drug accumulation, elevated DNA repair rates, altered topoisomerase activity, and enhanced drug detoxification are associated with development of the drug-resistant phenotype (1-3).The glutathione S-transferases (GST; RX:glutathione Rtransferase; EC 2.5.1.18) are a family of dimeric isozymes that can confer resistance to (detoxify) xenobiotic molecules by several mechanisms (1-3). In one mechanism, GSTs catalyze the covalent addition of the tripeptide glutathione to electrophilic molecules, including products of the cytochrome P-450 mixed-function oxidases, yielding conjugat...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Expression of recombinant glutathione S-transferase pi, Ya, or Yb1 confers resistance to alkylating agents.

Puchalski

Fahl²

1990

Proc. Natl. Acad. Sci. U.S.A.

129

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“…11) In our previous study we demonstrated that EA induced apoptosis in a mouse colon carcinoma cell line. 10) Since EA, used as a diuretic drug in the past, is a modifier of SH residues of many proteins 18,19) as well as a GST inhibitor, 20,21) these actions of EA may be partly involved in apoptosis induction.…”

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confidence: 99%

Characterization of cell death induced by ethacrynic acid in a human colon cancer cell line DLD‐1 and suppression by N‐acetyl‐l‐cysteine

et al. 2003

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Since ethacrynic acid (EA), an SH modifier as well as glutathione S-transferase (GST) inhibitor, has been suggested to induce apoptosis in some cell lines, its effects on a human colon cancer cell line DLD-1 were examined. EA enhanced cell proliferation at 20-40 µ µ µ µM, while it caused cell death at 60-100 µ µ µ µM. Caspase inhibitors did not block cell death and DNA ladder formation was not detected. Poly(ADP-ribose) polymerase, however, was cleaved into an 82-kDa fragment, different from an 85-kDa fragment that is specific for apoptosisis. The 82-kDa fragment was not recognized by antibody against PARP fragment cleaved by caspase 3. N-Acetyl-L-cysteine (NAC) completely inhibited EA-induced cell death, but 3(2)-t-butyl-4-hydroxyanisole or pyrrolidinedithiocarbamate ammonium salt did not. Glutathione (GSH) levels were dose-dependently increased in cells treated with EA and this in-

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“…Increased levels of GST have been shown to decrease toxicities of electrophilic agents, while treatment with electrophilic drugs has resulted in the induction of GST [1,3,5,[10][11][12][13][14]. In addition, GST and GSH depletions have been shown to increase the toxicity of several electrophilic drugs.…”

Section: Introductionmentioning

confidence: 99%

Effect of cisplatin on the expression of glutathione-S-transferase in the cochlea of the rat

Touliatos

Neitzel

Whitworth

et al. 2000

European Archives of Oto-Rhino-Laryngology

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Glutathione-S-transferase (GST) has been found to conjugate glutathione (GSH) to diverse electrophiles and play a major role in the detoxification of alkylating and platinating agents. However, there is little information regarding the pattern of GST expression in the cochlea. Although cisplatin is ototoxic, its effect on GST in the cochlea is unknown. In the present study we investigated the pattern of GST expression in control and cisplatin-treated cochleas by using the laboratory rat as animal model. Sixteen mature rats were randomly assigned to control or cisplatin groups. After treatment, cochleas were procured and tissues stained by immunohistochemical methods to detect the presence of GST. Optical density measurements were determined to gauge intensity of GST immunostaining. Strong positive GST immunostaining was demonstrated in all cochleas, with the most intense staining found in the spiral ligament and the least in Reissner's membrane. Mean optic density scores were lower for cisplatin-treated cochleas than for control cochleas in all areas analyzed. These findings showed that GST is expressed throughout the rat cochlea, with cisplatin treatment causing its decreased expression.

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Inhibition of soluble glutathione S-transferase by diuretic drugs

Cited by 51 publications

References 4 publications

Expression of recombinant glutathione S-transferase pi, Ya, or Yb1 confers resistance to alkylating agents.

Expression of recombinant glutathione S-transferase pi, Ya, or Yb1 confers resistance to alkylating agents.

Characterization of cell death induced by ethacrynic acid in a human colon cancer cell line DLD‐1 and suppression by N‐acetyl‐l‐cysteine

Effect of cisplatin on the expression of glutathione-S-transferase in the cochlea of the rat

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