Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cells.
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.
Chopin
Valérie
V
Laboratoire de Biologie du Développement, Equipe facteurs de croissance (UPRES 1033), Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France.
Toillon
Robert-Alain
RA
Jouy
Nathalie
N
Le Bourhis
Xuefen
X
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D052160:Benzothiazoles; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D002087:Butyrates / Q000494:pharmacology*; D061945:Caspase Inhibitors; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000187:drug effects / Q000378:metabolism*
D052160:Benzothiazoles; D002087:Butyrates; D061945:Caspase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D014050:Toluene; C121565:pifithrin