Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cells

被引:83
作者
Chopin, V
Toillon, RA
Jouy, N
Le Bourhis, X [1 ]
机构
[1] Univ Sci & Technol Lille, Equipe Facteurs Croissance UPRES 1033, Dev Biol Lab, F-59655 Villeneuve Dascq, France
[2] Inst Rech Canc Lille, Inst Federatif Rech Biol & Pathol Regulat Cellula, F-59045 Lille, France
关键词
apoptosis; breast cancer; cell growth; Fas; P53; sodium butyrate;
D O I
10.1038/sj.bjp.0704456
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 GI 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.
引用
收藏
页码:79 / 86
页数:8
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