2DG enhances the susceptibility of breast cancer cells to doxorubicin

Iman M. Ahmad, Ebtihal H. Mustafa, Noor H. Mustafa, Lubna H. Tahtamouni, Maher Y. Abdalla

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

2DG causes cytotoxicity in cancer cells by disrupting thiol metabolism while Doxorubicin (DOX) induces cytotoxicity in tumor cells by generating reactive oxygen species (ROS). Here we examined the combined cytotoxic action of 2DG and DOX in rapidly dividing T47D breast cancer cells vs. slowly growing MCF-7 breast cancer cells. T47D cells exposed to the combination of 2DG/DOX significantly decreased cell survival compared to controls, while 2DG/DOX had no effect on MCF-7 cells. 2DG/DOX also disrupted the oxidant status of T47D treated cells, decreased intracellular total glutathione and increased glutathione disulfide (%GSSG) compared to MCF-7 cells. Lipid peroxidation increased in T47D cells treated with 2DG and/or DOX, but not in MCF-7 cells. T47D cells were significantly protected by NAC, indicating that the combined treatment exerts its action by increasing ROS production and disrupting antioxidant stores. When we inhibited glutathione synthesis with BSO, T47D cells became more sensitive to 2DG/DOX-induced cytotoxicity, but NAC significantly reversed this cytotoxic effect. Finally, 2DG/DOX, and BSO significantly increased the %GSSG in T47D cells, an effect which was also reversed by NAC. Our results suggest that exposure of rapidly dividing breast cancer cells to 2DG/DOX enhances cytotoxicity via oxidative stress and via disruptions to thiol metabolism.

Original languageEnglish (US)
Pages (from-to)739-748
Number of pages10
JournalCentral European Journal of Biology
Volume5
Issue number6
DOIs
StatePublished - Jul 13 2010

Fingerprint

doxorubicin
breast neoplasms
Doxorubicin
Cells
Breast Neoplasms
cytotoxicity
Cytotoxicity
Glutathione Disulfide
cells
MCF-7 Cells
glutathione
thiols
Sulfhydryl Compounds
Metabolism
Glutathione
reactive oxygen species
Reactive Oxygen Species
neoplasm cells
metabolism
Oxidative stress

Keywords

  • 2DG
  • BSO
  • Breast cancer
  • Doxorubicin
  • GSH
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

2DG enhances the susceptibility of breast cancer cells to doxorubicin. / Ahmad, Iman M.; Mustafa, Ebtihal H.; Mustafa, Noor H.; Tahtamouni, Lubna H.; Abdalla, Maher Y.

In: Central European Journal of Biology, Vol. 5, No. 6, 13.07.2010, p. 739-748.

Research output: Contribution to journalArticle

Ahmad, Iman M. ; Mustafa, Ebtihal H. ; Mustafa, Noor H. ; Tahtamouni, Lubna H. ; Abdalla, Maher Y. / 2DG enhances the susceptibility of breast cancer cells to doxorubicin. In: Central European Journal of Biology. 2010 ; Vol. 5, No. 6. pp. 739-748.
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