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Modulation of the multidrug resistance of glioma by glutathione levels depletion--interaction with TC-99M-sestamibi and TC-99M-tetrofosmin
journal contributionposted on 2002-06-01, 00:00 authored by N Perek, F Koumanov, Delphine Denoyer, D Boudard, F Dubois
We have investigated the effect of glutathione (GSH) depletion on the chemosensitivity of human malignant glioma cell lines: G111, G5 and G152. All the cell lines showed a multidrug resistant (MDR) phenotype associated with MRP1 expression, high intracellular levels of GSH, and depolarized plasma membranes. Tc-99M-Sestamibi (MIBI) and Tc-99M-Tetrofosmin (Tfos) were used for monitoring the MDR mechanisms. Modulation of GSH content was performed with butoxysulfoximide (BSO) pre-treatment alone or in combination with GSH ethyl ester. MIBI and Tfos accumulation in the cells was inversely correlated to the GSH content, a higher accumulation was found after BSO pre-treatment and addition of GSH ethyl ester reversed this process. BSO could therefore play a role as a chemosensitizing drug and thus help to overcome MDR. However, higher accumulation of MIBI and Tfos was observed even in the sensitive cells suggesting another effect of BSO on the cell physiological characteristics. No sign of apoptosis has been found indicating a possible direct effect on the plasma membrane fluidity and permeability. MIBI and Tfos don't follow the expected behavior of a MDR probe in the glioma cells and given the particular morpho-physiological characteristics of these types of tumors, Tfos could be rather used as a marker of the tumor growth and proliferation.
JournalCancer biotherapy & radiopharmaceuticals
Pagination291 - 302
PublisherMary Ann Liebert, Inc. Publishers
LocationNew Rochelle, N.Y.
Publication classificationC1.1 Refereed article in a scholarly journal
Copyright notice2002, Mary Ann Liebert, Inc.
CategoriesNo categories selected
Annexin A5AntimetabolitesApoptosisBlotting, WesternButhionine SulfoximineDrug Resistance, MultipleDrug Resistance, NeoplasmGliomaGlutathioneHumansMembrane PotentialsMitochondriaMultidrug Resistance-Associated ProteinsOrganophosphorus CompoundsOrganotechnetium CompoundsP-GlycoproteinsRadiopharmaceuticalsTechnetium Tc 99m SestamibiTumor Cells, CulturedScience & TechnologyLife Sciences & BiomedicineOncologyMedicine, Research & ExperimentalPharmacology & PharmacyRadiology, Nuclear Medicine & Medical ImagingResearch & Experimental Medicinemultidrug resistanceTc-99m-tetrofosminTc-99m-sestamibibutoxysulfoximideCELL-LINESP-GLYCOPROTEINTC-99M SESTAMIBICULTURED NEURONSDRUG-RESISTANCEGENE-EXPRESSIONBREAST-CANCERTUMOR-CELLSPROTEIN MRP