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Abstract

The effects of glutathione (GSH) depletion by buthionine-S,R-sulphoximine (BSO) on MCF-7, a human cell line which exhibits high levels of GSH, were investigated. Pre-incubation with 5μM BSO for 48 hours significantly decreases GSH content in these cells and the depletion lasts as long as BSO is present in the culture medium. The cytotoxic activity of two antineoplastic agents, doxorubicin (DXR) and cisplatin (CDDP), whose interaction with GSH metabolism is known, was tested to evaluate whether GSH depletion would enhance the effectiveness of these compounds on MCF-7 cells. The results showed no significant improvement of the cytotoxic effect of either compound, suggesting the presence of concurrent mechanisms (e.g. interactions with enzymatic activities or intracellular macromolecular components), which may explain the positive results obtained with GSH depletion in other cell lines and in animal tumour models in vivo.

Keywords

glutathione human tumour cells buthionine-S,R-sulphoximine adriamycin cisplatin

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In Vitro Modulation of Glutathione Levels by Buthionine-S,R-Sulphoximine in a Human Cell Line: Effect on Cytotoxicity

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