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  • Title: Effect of glutathione depletion on cisplatin resistance in cancer cells transfected with the gamma-glutamylcysteine synthetase gene.
    Author: Kurokawa H, Nishio K, Ishida T, Arioka H, Fukuoka K, Nomoto T, Fukumoto H, Yokote H, Saijo N.
    Journal: Jpn J Cancer Res; 1997 Feb; 88(2):108-10. PubMed ID: 9119737.
    Abstract:
    Overexpression of the human gamma-glutamylcysteine (gamma-GCS) gene resulted in cisplatin resistance with an increased glutathione (GSH) content, increased ATP-dependent glutathione S-conjugate export pump (GS-X pump) activity and decreased platinum accumulation in human lung cancer cells transfected with a gamma-GCS cDNA expression vector, as we previously reported. In this study, we examined the effects of buthionine sulfoximine (BSO), a specific inhibitor of gamma-GCS, to determine whether GSH depletion alters cisplatin resistance in a gamma-GCS-transfected cell line, SBC-3/GCS. In the presence of 10 microM BSO for 4 days, SBC-3/GCS still showed resistance to cisplatin, although it was partially reversed. Under these conditions, GS-X pump activity remained up-regulated in spite of low GSH content, and the platinum content was decreased. These data suggest that the GS-X pump itself influences cisplatin resistance, as well as cellular GSH content.
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