Ascorbic acid and cell survival of adriamycin resistant and sensitive MCF-7 breast tumor cells

Wells, William W.; Rocque, Pamela A.; Xu, Dian; Meyer, Elizabeta B; Charamella, Leigh J.; Dimitrov, Nikolay V.

doi:10.1016/0891-5849(94)00188-p

Cited by 36 publications

(16 citation statements)

References 37 publications

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“…a Reactions were done at 30°C and contained 0.5 mM GSH, 0. tein glutathionylation is not yet known, however, it is possible that glutathionylation acts to protect cellular proteins by reversibly binding to sensitive sulfhydryls during times of oxidative stress [1]. Recently was reported [20] that TTase levels are lower in a variety of chemically transformed cells when compared to the untransformed cell type, suggesting that variations in TTase levels may have important cellular consequences. The creation of mammalian cell lines that over-and under-express TTase will provide an experimental paradigm in which the cellular functions of TTase can be studied more directly, including the effect TTase has on protein glutathionylation.…”

Section: Discussionmentioning

confidence: 99%

Cloning, expression and characterization of human thioltransferase (glutaredoxin) in E. coli

et al. 1995

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PCR primers were designed from the known amino acid (aa) sequence for human red blood cell thioltransferase (hRBC TTase) and the known cDNA sequence for pig liver TTase (82% homologous) and used to amplify thioltransferase from a pool of human brain cDNAs. The PCR product was inserted into the pKK233-2 expression vector. The DNA sequence of the insert agreed with the aa sequence. High level expression of the enzyme was accomplished in E. coli, and Western blot analysis confirmed its identity. Recombinant TTase displayed catalytic properties indistinguishable from natural hRBC TTase.

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Section: Discussionmentioning

confidence: 99%

Cloning, expression and characterization of human thioltransferase (glutaredoxin) in E. coli

et al. 1995

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“…Paradoxically, anticancer activity of very high doses of intravenous ascorbate is most likely based on prooxidant effects via H 2 O 2 formation through autoxidation that occurs in the extracellular fluid but not in whole blood, indicating that ascorbate at chemotherapeutic concentrations in blood serves as a prodrug for H 2 O 2 delivery to tissue (62)(63)(64). It is also possible that, after spontaneous oxidation of ascorbate to the semidehydroascorbyl free radical, chemical dismutation generates ascorbic acid and dehydroascorbic acid, the oxidized form of ascorbate actively transported into cells and transformed to ascorbic acid in a reductive enzymatic process that is glutathione-dependent and may therefore induce cellular glutathione depletion (367). Indeed, ascorbic acidinduced glutathione depletion enhances As 2 O 3 induced apoptosis in animal models of lymphoma and leukemia, and the minimal toxicity of infusional ascorbic acid compares favorably with other glutathione-depleting agents discussed below (18,135).…”

Section: H Sacrificial Antioxidants: L-ascorbatementioning

confidence: 99%

Redox-Directed Cancer Therapeutics: Molecular Mechanisms and Opportunities

Wondrak

2009

Antioxidants & Redox Signaling

417

352

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“…In theory, the most straightforward way to modulate Grx activity in situ is to change the content of active enzyme by altering rates of its production or degradation. Although little is known about the transcriptional regulation of Grx1, some hormonal and metabolic stimuli are associated with increased protein content and activity, including doxorubicin (Adriamycin) treatment of MCF-7 breast cancer cells (140), estradiol treatment of cardiomyoblasts (134), MPTP exposure in male mice (63), and culture of retinal Mü ller cells in high-glucose media (115). Recently, Grx2 mRNA was found to be elevated in peripheral blood mononuclear cells treated with the antitumor agent imexon (6), presumably via a putative antioxidant response element (ARE) in its promoter sequence.…”

Section: Enzyme Concentrationmentioning

confidence: 99%

Mechanistic and Kinetic Details of Catalysis of Thiol-Disulfide Exchange by Glutaredoxins and Potential Mechanisms of Regulation

Gallogly

Starke

Mieyal

2009

Antioxidants & Redox Signaling

201

209

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Glutaredoxins are small, heat-stable proteins that exhibit a characteristic thioredoxin fold and a CXXC=S activesite motif. A variety of glutathione (GSH)-dependent catalytic activities have been attributed to the glutaredoxins, including reduction of ribonucleotide reductase, arsenate, and dehydroascorbate; assembly of iron sulfur cluster complexes; and protein glutathionylation and deglutathionylation. Catalysis of reversible protein glutathionylation by glutaredoxins has been implicated in regulation of redox signal transduction and sulfhydryl homeostasis in numerous contexts in health and disease. This forum review is presented in two parts. Part I is focused primarily on the mechanism of the deglutathionylation reaction catalyzed by prototypical dithiol glutaredoxins, especially human Grx1 and Grx2. Grx-catalyzed protein deglutathionylation proceeds by a nucleophilic, double-displacement mechanism in which rate enhancement is attributed to special reactivity of the low pK a cysteine at its active site, and to increased nucleophilicity of the second substrate, GSH. Glutaredoxins (and Grx domains) have been identified in most organisms, and many exhibit deglutathionylation or other activities or both. Further characterization according to glutathionyl selectivity, physiological substrates, and intracellular roles may lead to subclassification of this family of enzymes. Part II presents potential mechanisms for in vivo regulation of Grx activity, providing avenues for future studies. Antioxid. Redox Signal. 11, 1059-1081.Part I: Glutaredoxins and Catalysis of Thiol-Disulfide Exchange G lutaredoxins are GSH-disulfide oxidoreductases reported to catalyze a variety of GSH-dependent thioldisulfide exchange reactions including protein glutathionylation and deglutathionylation, turnover of ribonucleotide reductase, and reduction of dehydroascorbate and arsenate; and some glutaredoxins are also implicated in FeS cluster homeostasis (reviewed in refs. 68, 80, 81). Among the reported catalytic activities of the glutaredoxins, protein deglutathionylation (reduction of protein-glutathione mixed disulfides, protein-SSG) has received much attention because of its regulatory roles in redox signal transduction and sulfhydryl homeostasis (reviewed in refs. 23, 80). Glutathionylation is an oxidative posttranslational modification that occurs on some protein cysteines under basal conditions [e.g., b-actin (137), mitochondrial complex II (19)]; for others, it is a transient modification that occurs during oxidative stresses such as ischemia=reperfusion [e.g., a-actin (18), GAPDH (26), mitochondrial complex I (56)]. For many proteins, glutathionylation affects function, and thus the reversible glutathionylation of specific proteins has been implicated in regulation of cellular homeostasis in health and disease (reviewed in refs. 23, 80). Grx is the primary intracellular deglutathionylating enzyme in mammalian cells (21,52), and manipulation of Grx levels has been shown to affect protein glutathionylation status and, subs...

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Ascorbic acid and cell survival of adriamycin resistant and sensitive MCF-7 breast tumor cells

Cited by 36 publications

References 37 publications

Cloning, expression and characterization of human thioltransferase (glutaredoxin) in E. coli

Cloning, expression and characterization of human thioltransferase (glutaredoxin) in E. coli

Redox-Directed Cancer Therapeutics: Molecular Mechanisms and Opportunities

Mechanistic and Kinetic Details of Catalysis of Thiol-Disulfide Exchange by Glutaredoxins and Potential Mechanisms of Regulation

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