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Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cells
- Publication Year :
- 2002
-
Abstract
- 1. This study was performed to determine the effect and action mechanisms of sodium butyrate (NaB) on the growth of breast cancer cells. 2. Butyrate inhibited the growth of all breast cancer cell lines analysed. It induced cell cycle arrest in G1 and apoptosis in MCF-7, MCF-7ras, T47-D, and BT-20 cells, as well as arrest in G2/M in MDA-MB-231 cells. 3. Transient transfection of MCF-7 and T47-D cells with wild-type and antisense p53 did not modify butyrate-induced apoptosis. Pifithrin-alpha, which inhibits the transcriptional activity of P53, did not modify cell growth or apoptosis of MCF-7 and T47-D cells treated with butyrate. These results indicate that P53 was not involved in butyrate-induced growth inhibition of breast cancer cells. 4. Treatment of MCF-7 cells with anti-Fas agonist antibody induced cell death, indicating that Fas was functional in these cells. Moreover, butyrate potentiated Fas-induced apoptosis, as massive apoptosis was observed rapidly when MCF-7 cells were treated with butyrate and anti-Fas agonist antibody. In addition, butyrate-induced apoptosis in MCF-7 cells was considerably reduced by anti-Fas antagonist antibody. Western blot analysis showed that butyrate increased Fas and Fas ligand levels (Fas L), indicating that butyrate-induced apoptosis may be mediated by Fas signalling. 5. These results demonstrate that butyrate inhibited the growth of breast cancer cells in a P53-independent manner. Moreover, it induced apoptosis via the Fas/Fas L system and potentiated Fas-triggered apoptosis in MCF-7 cells. These findings may open interesting perspectives in human breast cancer treatment strategy.
- Subjects :
- Fas Ligand Protein
Membrane Glycoproteins
Blotting, Western
Cell Cycle
Apoptosis
Breast Neoplasms
Caspase Inhibitors
Butyrates
Thiazoles
Proto-Oncogene Proteins c-bcl-2
Proto-Oncogene Proteins
Papers
Tumor Cells, Cultured
Humans
Benzothiazoles
fas Receptor
Tumor Suppressor Protein p53
skin and connective tissue diseases
Cell Division
Signal Transduction
Toluene
bcl-2-Associated X Protein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.pmid..........929ad1b7668fd64d066bdeeb349f9f24