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Modulation of sensitivity to doxorubicin by the histone deacetylase inhibitor sodium butyrate in breast cancer cells
- Source :
- International journal of oncology. 26(6)
- Publication Year :
- 2005
-
Abstract
- The histone deacetylase inhibitor sodium butyrate induces several gene products that modify cellular metabolism. Here, we investigated its ability to modulate glutathione-related detoxification enzymes in the breast cancer cell line MCF-7 and a derivative resistant to vincristine (VCREMS). We found that sodium butyrate induced glutathione S-transferase and glutathione-dependent peroxidase activities and triggered glutathione depletion. Expression of MRP1, an ATP-dependent GS-X pump, was unmodified. Moreover, isobologram analysis showed that sodium butyrate sensitized VCREMS to doxorubicin-mediated toxicity. Verapamil, an inhibitor of MRP1, did not significantly affect this chemosensitizing effect, suggesting that the observed toxicity stems from multifactorial mechanisms. Interestingly, synergism between sodium butyrate and doxorubicin was more pronounced in resistant VCREMS cells than in parental sensitive MCF-7 cells.
- Subjects :
- Cancer Research
medicine.drug_class
Breast Neoplasms
Butyric acid
chemistry.chemical_compound
Cell Line, Tumor
medicine
Humans
Doxorubicin
Enzyme Inhibitors
biology
Histone deacetylase inhibitor
Sodium butyrate
Drug Synergism
Glutathione
Histone Deacetylase Inhibitors
Butyrates
Oncology
chemistry
Verapamil
Enzyme inhibitor
Vincristine
Cancer research
biology.protein
Female
Histone deacetylase
Peroxidase
medicine.drug
Subjects
Details
- ISSN :
- 10196439
- Volume :
- 26
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- International journal of oncology
- Accession number :
- edsair.doi.dedup.....5339664399650ccc46a4f005a1fd1a04