Sulfasalazine-induced reduction of glutathione levels in breast cancer cells: Enhancement of growth-inhibitory activity of doxorubicin
Document Type
Article
Publication Title
Chemotherapy
Abstract
Background: We previously showed that the anti-inflammatory drug, sulfasalazine (salicylazosulfapyridine, SASP), can arrest proliferation of MCF-7 and MDA-MB-231 mammary cancer cells by inhibiting uptake of cystine via the xc- cystine/glutamate antiporter. Here we examined SASP with regard to reduction of cellular glutathione (GSH) levels and drug efficacy-enhancing ability. Methods: GSH levels were measured spectrophotometrically. Cellular drug retention was determined with 3H-labeled methotrexate, and drug efficacy with a colony formation assay. Results: Incubation of the mammary cancer cells with SASP (0.3-0.5 mM) led to reduction of their GSH content in a time- and concentration-dependent manner. Similar to MK-571, a multidrug resistance-associated protein inhibitor, SASP increased intracellular accumulation of methotrexate. Preincubation of cells with SASP (0.3 mM) significantly enhanced the potency of the anticancer agent doxorubicin (2.5 nM). Conclusions: SASP-induced reduction of cellular GSH levels can lead to growth arrest of mammary cancer cells and enhancement of anticancer drug efficacy. Copyright © 2007 S. Karger AG.
First Page
210
Last Page
217
DOI
10.1159/000100812
Publication Date
4-1-2007
Recommended Citation
Narang, Vishal S.; Pauletti, Giovanni M.; Gout, Peter W.; Buckley, Donna J.; and Buckley, Arthur R., "Sulfasalazine-induced reduction of glutathione levels in breast cancer cells: Enhancement of growth-inhibitory activity of doxorubicin" (2007). Pharmaceutical and Administrative Sciences Faculty Publications. 178.
https://doi.org/10.1159/000100812
https://collections.uhsp.edu/pharm-admin-sciences_pubs/178