Acidic pH of Tumor Microenvironment Enhances Cytotoxicity of the Disulfiram/Cu2+ Complex to Breast and Colon Cancer Cells

作者：Navratilova Jarmila; Hankeova Tereza; Benes Petr; Smarda Jan^*

来源：Chemotherapy, 2013, 59(2): 112-120.

DOI：10.1159/000353915

• Breast cancer
• Colon cancer
• Cytotoxicity
• Disulfiram Reactive oxygen species
• Tumor microenvironment

Background: 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 microenvironnnent, such as oxygen depletion (hypoxia), glucose/energy deprivation and acidosis. Methods:The effects of acidic tumor-like microenvironment on cytotoxicity of antabuse (disulfiram, DSF)/ Cu2+ complexes to MCF-7 breast carcinoma and HT-29 colon carcinoma cells were studied. Results: We show that acidic pH significantly potentiates toxicity of DSF/Cu2+ complex to breast and colon cancer cells. This phenomenon is associated with changes in cell metabolism, altered Akt kinase and NFKB activity and increased reactive oxygen species production. Conclusion: Specific pH of tumor microenvironnnent enhances cytotoxicity of DSF/Cu2+ to breast and colon cancer cells.

• 出版日期2013