2003
DOI: 10.1038/sj.bjc.6600786
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Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines

Abstract: Transport system x c À is a member of plasma membrane heterodimeric amino-acid transporters and consists of two protein components, xCT and 4F2hc. This system mediates cystine entry coupled with the exodus of intracellular glutamate and regulates the intracellular glutathione (GSH) levels in most mammalian cultured cells. We studied the activity of system x c À and GSH content in human ovarian cancer cell line (A2780) and its cisplatin (CDDP)-resistant variant (A2780DDP). The rate of cystine uptake was approxi… Show more

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Cited by 163 publications
(138 citation statements)
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“…The importance of the cystine/cysteine cycle for the resistance of cancer cells to chemotherapy has been recognized only recently (Okuno et al, 2003). Activation of the xCT gene in cancer cells by cytotoxic drugs may be a mechanism contributing to chemotherapy resistance in vivo, a possibility that apparently deserves further studies.…”
Section: Discussionmentioning
confidence: 99%
“…The importance of the cystine/cysteine cycle for the resistance of cancer cells to chemotherapy has been recognized only recently (Okuno et al, 2003). Activation of the xCT gene in cancer cells by cytotoxic drugs may be a mechanism contributing to chemotherapy resistance in vivo, a possibility that apparently deserves further studies.…”
Section: Discussionmentioning
confidence: 99%
“…Intracellular cystine is rapidly reduced to cysteine and incorporated into thiol containing proteins and GSH. xCT activity correlates with cellular GSH levels in a variety of cell types [37] and 3T3 cells that overexpress xCT were found to contain greater levels GSH than vector control cells ( Figure. 3A).…”
Section: Xct Overexpression Increases Intracellular Reduced Thiol Levmentioning
confidence: 99%
“…The major antioxidant within cells is glutathione, a tripeptide that is synthesized from cysteine, glutamate, and glycine (18). Cystine is taken up by cells primarily through the xC(-) system, which is a heterodimeric protein consisting of a transporter subunit (xCT, encoded by the SLC7A11 gene) and a regulatory subunit (4F2hc, also known as CD98, encoded by the SLC3A2 gene) (19). In cells, cystine is reduced to cysteine and reacts with glutamate to form γ-glutamylcysteine in…”
mentioning
confidence: 99%