Cell death induced by taxanes in breast cancer cells: cytochrome C is released in resistant but not in sensitive cells
Language English Country Greece Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16309219
Knihovny.cz E-resources
- MeSH
- Cell Death drug effects physiology MeSH
- Cell Growth Processes drug effects MeSH
- Drug Resistance, Neoplasm MeSH
- Cytochromes c metabolism MeSH
- Docetaxel MeSH
- DNA Fragmentation drug effects MeSH
- Antineoplastic Agents, Phytogenic pharmacology MeSH
- Cyclin-Dependent Kinase Inhibitor p21 biosynthesis MeSH
- Caspase 3 MeSH
- Caspase 9 MeSH
- Caspases metabolism MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 biosynthesis MeSH
- Breast Neoplasms drug therapy metabolism pathology MeSH
- Paclitaxel pharmacology MeSH
- Taxoids pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- CASP3 protein, human MeSH Browser
- CASP9 protein, human MeSH Browser
- CDKN1A protein, human MeSH Browser
- Cytochromes c MeSH
- Docetaxel MeSH
- Antineoplastic Agents, Phytogenic MeSH
- Cyclin-Dependent Kinase Inhibitor p21 MeSH
- Caspase 3 MeSH
- Caspase 9 MeSH
- Caspases MeSH
- Tumor Suppressor Protein p53 MeSH
- Paclitaxel MeSH
- Taxoids MeSH
- TP53 protein, human MeSH Browser
BACKGROUND: The aim of the study was to contribute to our understanding of the mechanisms responsible for the resistance of breast cancer cells to taxanes. MATERIALS AND METHODS: Cell cycle characteristics, DNA fragmentation, p53 and p21(WAF1/CIP1) expression, caspase-3 and caspase-9 activity, cytochrome c release from mitochondria during cell death induction by the taxanes paclitaxel and docetaxel in highly-sensitive MDA-MB-435 and highly-resistant NCI-ADR-RES human breast cancer cells were compared. RESULTS: Approximately 300-fold higher concentrations of the taxanes were required to induce death in resistant NCI-ADR-RES cells than in sensitive MDA-MB-435 cells. Cell death induced by the taxanes in both sensitive and resistant cells was preceded by the accumulation of cells in the G2/M-phase. Neither cell type produced any DNA fragmentation (DNA ladder) typical of regular apoptosis. The p53 and the p21(WAF1/CIP1) levels did not change in sensitive or in resistant cells during cell death induction by the taxanes. The activity of the executioner caspase-3 increased significantly (2 to 2.5-fold) and, similarly, the activity of caspase-9 increased significantly (2 to 3.5-fold) in both cell types. However, cytochrome c was found to be released from mitochondria into the cytosol only in the resistant NCI-ADR-RES cells, but not in the sensitive MDA-MB-435 cells. CONCLUSION: The death induced by the taxanes in the studied breast cancer cells can be characterized as an apoptosis-like death, including caspase-3 and caspase-9 activation but not oligonucleosomal DNA fragmentation. However, the mechanisms of death induction by the taxanes in sensitive MDA-MB-435 cells and resistant NCI-ADR-RES cells differ. Cytochrome c is released from the mitochondria in resistant but not in sensitive cells.
The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes
The role of individual caspases in cell death induction by taxanes in breast cancer cells
Cell death induced by novel fluorinated taxanes in drug-sensitive and drug-resistant cancer cells
