Sulfasalazine-induced reduction of glutathione levels in breast cancer cells: enhancement of growth-inhibitory activity of Doxorubicin
| Autor: | Vishal S Narang, Donna J. Buckley, Arthur R. Buckley, Giovanni M. Pauletti, Peter W. Gout |
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| Rok vydání: | 2005 |
| Předmět: |
Antimetabolites
Antineoplastic ATP Binding Cassette Transporter Subfamily B Breast Neoplasms Drug resistance Pharmacology chemistry.chemical_compound Sulfasalazine Cell Line Tumor Drug Discovery medicine Neoplasm Humans Pharmacology (medical) Doxorubicin ATP Binding Cassette Transporter Subfamily B Member 1 skin and connective tissue diseases Tumor Stem Cell Assay Cell Proliferation Antibiotics Antineoplastic Chemistry fungi Anti-Inflammatory Agents Non-Steroidal Carcinoma food and beverages Drug Synergism General Medicine Glutathione medicine.disease Infectious Diseases Methotrexate Oncology Cell culture Drug Resistance Neoplasm Cancer cell Quinolines Propionates Oxidation-Reduction medicine.drug |
| Zdroj: | Chemotherapy. 53(3) |
| ISSN: | 1421-9794 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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