Suppression of cystine uptake by sulfasalazine inhibits proliferation of human mammary carcinoma cells.
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 xc- in mammary cancer cell lines.


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 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.


CONCLUSIONS
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.
Narang
Vishal S
VS
College of Pharmacy, University of Cincinnati, 3223 Eden Ave., Cincinnati, OH 45267-0004, USA.
Pauletti
Giovanni M
GM
Gout
Peter W
PW
Buckley
Donna J
DJ
Buckley
Arthur R
AR
D001692:Biological Transport / Q000187:drug effects*; D001940:Breast / Q000166:cytology / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003553:Cystine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D007700:Kinetics; D012460:Sulfasalazine / Q000494:pharmacology*; D013462:Sulfur Radioisotopes; D014407:Tumor Cells, Cultured
D013462:Sulfur Radioisotopes; D012460:Sulfasalazine; D003553:Cystine