Acidic pH of tumor microenvironment enhances cytotoxicity of disulfiram/Cu2+ complex to breast and colon cancer cells
| Authors | |
|---|---|
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | CHEMOTHERAPY |
| MU Faculty or unit | |
| 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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