Increased rate of glutathione synthesis from cystine in drug-resistant MCF-7 cells

Gamcsik, Michael P.; Dubay, George R.; Cox, Brandon R.

doi:10.1016/s0006-2952(01)00931-5

Cited by 28 publications

(22 citation statements)

References 35 publications

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“…Expression of GST-Pi is associated with resistance to some antineoplastic drugs. Increased metabolic synthesis of glutathione was shown in drug-resistant MCF7 (Gamcsik et al, 2002). The increased synthetic rates of GSH in resistant lines reflected, in part, contributions from increased activities of GCS.…”

Section: Discussionmentioning

confidence: 96%

Transcriptional regulation by the estrogen receptor of antioxidative stress enzymes and its functional implications

et al. 2003

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We previously reported that antiestrogen-liganded estrogen receptor b (ERb) transcriptionally activates the major detoxifying enzyme quinone reductase (QR) (NAD(P)H:-quinone oxidoreductase). Our studies also indicate that upregulation of QR, either by overexpression or induction by tamoxifen, can protect breast cells against oxidative DNA damage caused by estrogen metabolites. We now report on the upregulation of glutathione S-transferases Pi (GST-Pi) and gamma-glutamylcysteine synthetase heavy subunit (GCSh) expression by antiestrogens. Studies indicate the regulation of GST-Pi and GCSh transcriptional activity by ER. While ER regulation is mediated by an electrophile response element (EpRE), we identified mechanistic differences in the involvement of other transcription factors. Regardless of these differences, ERb-mediated regulation of GST-Pi and GCSh point towards an important role for ERb in cellular protection against oxidative stress. A protective role is supported by our observation of inhibition of estrogeninduced DNA damage upon upregulation of GST-Pi and GCSh expression.

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Section: Discussionmentioning

confidence: 96%

Transcriptional regulation by the estrogen receptor of antioxidative stress enzymes and its functional implications

et al. 2003

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“…One reason for these contradictory results may be that single tumor biopsy specimens are not representative of the entire tumor (6). Another explanation is that the rate of glutathione metabolism, in addition to its steady-state level, is an important factor when evaluating therapeutic response (7,8). Clearly, an in vivo method that can noninvasively monitor glutathione metabolism would circumvent sampling problems and allow an assessment of metabolic rates.…”

Section: Introductionmentioning

confidence: 99%

“…Clearly, an in vivo method that can noninvasively monitor glutathione metabolism would circumvent sampling problems and allow an assessment of metabolic rates. We have therefore extended our studies developed in cell culture (7,8) to monitor glutathione metabolism in intact fibrosarcoma (FSA) tumors implanted s.c. in Fischer 344 rats. Glutathione biosynthesis from infused [2-13 C]glycine was observed by in vivo 13 C magnetic resonance spectroscopy and the heterogeneity of glutathione metabolism across the tumor tissue was detected using chemical shift imaging (CSI).…”

Section: Introductionmentioning

confidence: 99%

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Noninvasive In vivo Detection of Glutathione Metabolism in Tumors

Thelwall

Yemin

Gillian³

et al. 2005

Cancer Research

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Magnetic resonance spectroscopic imaging has been used to follow glutathione metabolism and evaluate glutathione heterogeneity in intact tumor tissue. Stable isotope-labeled glutathione was detected in s.c. implanted fibrosarcoma tumors in anesthetized rats following infusion of [2-13 C]glycine. Using 1 H-decoupled 13 C magnetic resonance spectroscopy, the appearance of [2-13 C]glycine at 42.4 ppm and the subsequent incorporation of this isotope label into the glycyl residue of glutathione at 44.2 ppm can be detected. The identity and relative concentrations of labeled metabolites observed in the in vivo spectrum were confirmed in studies of tissue extracts. The high level of isotopic enrichment and the concentration of glutathione in tumor tissue allow for collection of spatially localized spectra using 13 C chemical shift imaging methods. These data provide the first direct images of glutathione in intact tumor tissue and show metabolic heterogeneity. This method may lead to the ability to monitor changes in tumor tissue redox state that may ultimately affect diagnosis, monitoring, and treatment. (Cancer Res 2005; 65(22): 10149-53)

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“…nem-klasszikus illetve a transzportalapú klasszikus mechanizmusok. A nem-klasszikus mechanizmusok közé sorolhatjuk a droginaktivációt [18], a drog célmolekuláját érintő változásokat (megváltozott expressziós szint, mutáció) [19] valamint a drog-indukálta apoptózis elkerülését [20], míg a klasszikus MDR alatt a kemoterápiás szerek sejtből való eltávolítását értjük, amit különböző transzport fehérjék hajtanak végre [13,21].…”

Section: A Szerzett Multidrog Rezisztenciaunclassified

ABCB1 transzporterek vizsgálata multidrog rezisztens patkány hepatoma sejtekben

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Increased rate of glutathione synthesis from cystine in drug-resistant MCF-7 cells

Cited by 28 publications

References 35 publications

Transcriptional regulation by the estrogen receptor of antioxidative stress enzymes and its functional implications

Transcriptional regulation by the estrogen receptor of antioxidative stress enzymes and its functional implications

Noninvasive In vivo Detection of Glutathione Metabolism in Tumors

ABCB1 transzporterek vizsgálata multidrog rezisztens patkány hepatoma sejtekben

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