| Literature DB >> 9119737 |
H Kurokawa1, K Nishio, T Ishida, H Arioka, K Fukuoka, T Nomoto, H Fukumoto, H Yokote, N Saijo.
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.Entities:
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Year: 1997 PMID: 9119737 PMCID: PMC5921367 DOI: 10.1111/j.1349-7006.1997.tb00354.x
Source DB: PubMed Journal: Jpn J Cancer Res ISSN: 0910-5050