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Acidic pH of tumor microenvironment enhances cytotoxicity of the disulfiram/Cu2+ complex to breast and colon cancer cells
J. Navrátilová, T. Hankeová, P. Beneš, J. Šmarda,
Language English Country Switzerland
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT13441
MZ0
CEP Register
Digital library NLK
Full text - Article
Source
NLK
ProQuest Central
from 1998-01-01 to 2015-11-30
Health & Medicine (ProQuest)
from 1998-01-01 to 2015-11-30
PubMed
24051574
DOI
10.1159/000353915
Knihovny.cz E-resources
- MeSH
- HT29 Cells MeSH
- Disulfiram chemistry MeSH
- Phosphorylation MeSH
- Coordination Complexes chemical synthesis chemistry toxicity MeSH
- Hydrogen-Ion Concentration MeSH
- Humans MeSH
- Copper chemistry MeSH
- MCF-7 Cells MeSH
- Tumor Microenvironment drug effects MeSH
- Breast Neoplasms metabolism pathology MeSH
- Colonic Neoplasms metabolism pathology MeSH
- NF-kappa B metabolism MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents chemical synthesis chemistry toxicity MeSH
- Proto-Oncogene Proteins c-akt metabolism MeSH
- Reactive Oxygen Species metabolism MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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 microenvironment, such as oxygen depletion (hypoxia), glucose/energy deprivation and acidosis. METHODS: The effects of acidic tumor-like microenvironment on cytotoxicity of antabuse (disulfiram, DSF)/Cu(2+) 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/Cu(2+) complex to breast and colon cancer cells. This phenomenon is associated with changes in cell metabolism, altered Akt kinase and NFκB activity and increased reactive oxygen species production. CONCLUSION: Specific pH of tumor microenvironment enhances cytotoxicity of DSF/Cu(2+) to breast and colon cancer cells.
References provided by Crossref.org
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