Acidic pH of tumor microenvironment enhances cytotoxicity of disulfiram/Cu2+ complex to breast and colon cancer cells

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Authors

NAVRÁTILOVÁ Jarmila HANKEOVÁ Tereza BENEŠ Petr ŠMARDA Jan

Year of publication 2013
Type Article in Periodical
Magazine / Source CHEMOTHERAPY
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1159/000353915
Field Genetics and molecular biology
Keywords Breast cancer; Colon cancer; Cytotoxicity; Disulfiram; Reactive Oxygen Species; Tumor microenvironment
Description A resistance of cancer cells to chemotherapeutic agents is a major cause of treatment failure in patients with cancer. The drug-resistance of tumor cells can be significantly modified by specific features of tumor microenvironment, such as oxygen depletion (hypoxia), glucose/energy deprivation and acidosis. The effects of acidic tumor-like microenvironment on cytotoxicity of antabuse (disulfiram)/Cu2+ complexes to MCF-7 breast carcinoma and HT-29 colon carcinoma cells were studied. We show that acidic pH significantly potentiates toxicity of disulfiram/Cu2+ complex to breast and colon cancer cells. This phenomenon is associated with changes in cell metabolism, altered Akt kinase and NFkappaB activities and increased reactive oxygen species production. Conclusion: Specific pH of tumor microenvironment enhances cytotoxicity of disulfiram/Cu2+ to breast and colon cancer cells.
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