Suppression of Cystine Uptake by Sulfasalazine Inhibits Proliferation of Human Mammary Carcinoma Cells

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Anticancer Research


Background: Malignant 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 x c- in mammary cancer cell lines. Materials and Methods: Expression and function of xc- were evaluated by RT-PCR and 35S-cystine uptake analysis. Results: Xc- 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 μM), 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. Conclusion: The 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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