• Vishal S Narang, Giovanni M Pauletti, Peter W Gout, Donna J Buckley, and Arthur R Buckley.
• College of Pharmacy, University of Cincinnati, 3223 Eden Ave., Cincinnati, OH 45267-0004, USA.
• Anticancer Res. 2003 Nov 1; 23 (6C): 4571-9.

BackgroundMalignant progression of lymphoma cells is associated with acquisition of the cystine/glutamate antiporter, xc-, enhancing cystine uptake. Recently, we showed that sulfasalazine (SASP) is a specific xc- inhibitor. Here, we investigated xc- in mammary cancer cell lines.Materials And MethodsExpression and function of xc- were evaluated by RT-PCR and 35S-cystine uptake analysis.ResultsXc- expression was elevated 4-fold (p < 0.001) in cells of the most malignant line, MDA-MB-231, associated with increased 35S-cystine uptake (p < 0.001). Proliferation was inhibited by 0.2-0.5 mM SASP. 2-Mercaptoethanol (60 microM), a cystine uptake enhancer, completely prevented SASP-mediated growth inhibition in MDA-MB-231 cultures, but only partially in 184A1 and MCF-7 cultures. SASP-induced growth arrest was reversible and not cell cycle-specific.ConclusionThe results suggest: (i) malignant progression of human mammary cancer may be associated with acquisition of xc- expression potentially leading to increased growth autonomy and drug resistance, (ii) xc- may act as a therapeutic target.

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