Regulation of cellular glutathione modulates nuclear accumulation of daunorubicin in human MCF7 cells overexpressing multidrug resistance associated protein

Benderra, Zineb; Trussardi, Aurélie; Morjani, Hamid; Villa, Antonello; Doglia, Silvia Maria; Manfait, Michel

doi:10.1016/s0959-8049(99)00288-9

Cited by 55 publications

(44 citation statements)

References 24 publications

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“…4D) was significantly greater than that from MCF7-WT control cells (Fig. 4C) in the presence and absence of NO, because of higher expression of MRP1 in MCF7-VP cells than MCF7-WT cells (21,22). Incubation of MCF7-VP cells with MK571 significantly decreased GSH release compared with the control in the presence and absence of SperNO (0.5 mM) (Fig.…”

Section: Effect Of Mrp1 Inhibitors On Gsh Efflux From Mcf7-wt and Mcfmentioning

confidence: 82%

Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Watts

Hawkins

Ponka

et al. 2006

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

116

119

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Nitrogen monoxide (NO) plays a role in the cytotoxic mechanisms of activated macrophages against tumor cells by inducing iron (Fe) release. We have shown that NO-mediated Fe efflux from cells required glutathione (GSH), and we have hypothesized that a GS–Fe–NO complex was released. Hence, we studied the role of the GSH-conjugate transporter multidrug resistance-associated protein 1 (MRP1) in NO-mediated Fe efflux. MCF7-VP cells overexpressing MRP1 exhibited a 3- to 4-fold increase in NO-mediated 59 Fe and GSH efflux compared with WT cells (MCF7-WT) over 4 h. Similar results were found for other MRP1-overexpressing cell types but not those expressing another drug efflux pump, P-glycoprotein. NO-mediated 59 Fe and GSH efflux were temperature- and energy-dependent and were significantly decreased by the GSH-depleting agent and MRP1 transport inhibitor l -buthionine-[ S , R ]-sulfoximine. Other MRP1 inhibitors, MK571, probenecid, and difloxacin, significantly inhibited NO-mediated 59 Fe release. EPR spectroscopy demonstrated the dinitrosyl-dithiol-Fe complex (DNIC) peak in NO-treated cells was increased by MRP1 inhibitors, indicating inhibited DNIC transport from cells. The extent of DNIC accumulation correlated with the ability of MRP1 inhibitors to prevent NO-mediated 59 Fe efflux. MCF7-VP cells were more sensitive than MCF7-WT cells to growth inhibition by effects of NO, which was potentiated by l -buthionine-[ S , R ]-sulfoximine. These data indicate the importance of GSH in NO-mediated inhibition of proliferation. Collectively, NO stimulates Fe and GSH efflux from cells via MRP1. Active transport of NO by MRP1 overcomes diffusion that is inefficient and nontargeted, which has broad ramifications for understanding NO biology.

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Section: Effect Of Mrp1 Inhibitors On Gsh Efflux From Mcf7-wt and Mcfmentioning

confidence: 82%

Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Watts

Hawkins

Ponka

et al. 2006

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

116

119

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“…Modulation of MRP activity may be more difficult to achieve than modulation of Pgp [23]. When MRP is coexpressed, a Pgp modulator might partially reverse the response of the tumor cells to doxorubicin or other substrates of Pgp function without fully reversing the effects of MRP [32,33]. Posttranslational modification of Pgp has also been described and may alter the response to a Pgp modulator.…”

Section: Discussionmentioning

confidence: 99%

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

Liu

Stevenson

Barrett

et al. 2005

Nuclear Medicine and Biology

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Background-99m Tc-sestamibi (MIBI) and 99m Tc-tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging.Methods-Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session.Results-MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62 ± 0.15 vs. 0.55 ± 0.05, P <.05) for TF and 1.9-fold (1.21 ± 0.04 vs. 0.64 ± 0.05, P <.05) for MIBI but did not affect MCF7/WT.Conclusions-The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

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“…The fraction of viable cells was calculated by comparing the optical absorbance of the 5-FUor MMC-treated culture with that of the untreated control. The 50% inhibitory concentration (IC 50 ) value was calculated on the basis of the fraction of viable cells.…”

Section: Methodsmentioning

confidence: 99%

“…1, the cell viability gradually reduced concomitantly with the increase in BSO concentration. The IC 50 value of BSO in the SGC7901 cells, calculated using the Hill equation, was 3.43 mg/ml. There were non-significant reductions in the viabilities of the cells exposed to the various concentrations of BSO below 20% IC 50 (p>0.05).…”

Section: Selection Of the Sublethal Concentration Of Bsomentioning

confidence: 99%

Changes in intracellular redox status influence multidrug resistance in gastric adenocarcinoma cells

De-jun

Jin

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Multidrug resistance (MDR) to chemotherapeutic agents is a major obstacle for the treatment of various types of cancers. The exact mechanism of MDR has not yet been fully clarified, although it has been frequently associated with the variation of intracellular redox status. The levels of intracellular glutathione (GSH) are considered to play a vital role in the regulation of the intracellular redox status. In our study, we investigated the effects of buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis, and NAC, a cysteine source for GSH synthesis, on sensitive gastric adenocarcinoma cells (SGC7901) and cisplatin-resistant SGC7901/DDP cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The two cell lines were pretreated with various non-toxic concentrations of BSO for 24 h and combined with fluorouracil (5-FU) or mitomycin (MMC) in the presence or absence of NAC before culturing further. After various treatments, the IC 50 values of MMC and 5-FU were calculated and intracellular GSH levels were measured using the glutathione reductase/5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) recycling assay without anticancer drug stimulation under the same microenvironments. The study demonstrated that BSO increased the sensitivity of the cells to chemotherapeutics while NAC exhibited the reverse effect, particularly in drug-resistant cells. It is, therefore, possible that changes in intracellular GSH levels affect the chemosensitivity of the resistant cells to a greater extent than that of their parent cells. This study indicates that variation in the intracellular redox status may be closely correlated with MDR and may provide a valuable basic strategy for anticancer therapy.

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Regulation of cellular glutathione modulates nuclear accumulation of daunorubicin in human MCF7 cells overexpressing multidrug resistance associated protein

Cited by 55 publications

References 24 publications

Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

Changes in intracellular redox status influence multidrug resistance in gastric adenocarcinoma cells

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