2,6-bis((3,4-dihydroxyphenyl)-methylene)cyclohexanone (BDHPC)-induced apoptosis and p53-independent growth inhibition: Synergism with genistein

被引:6
作者
Attalla, H
Makela, TP
Wahala, K
Rasku, S
Andersson, LC
Adlercreutz, H
机构
[1] UNIV HELSINKI,DEPT CLIN CHEM,FIN-00290 HELSINKI,FINLAND
[2] UNIV HELSINKI,HAARTMAN INST,FIN-00290 HELSINKI,FINLAND
[3] UNIV HELSINKI,DEPT CHEM,FIN-00290 HELSINKI,FINLAND
[4] UNIV HELSINKI,DEPT PATHOL,FIN-00290 HELSINKI,FINLAND
[5] UNIV HELSINKI,FOLKHALSEN RES CTR,FIN-00290 HELSINKI,FINLAND
关键词
BDHPC; genistein; cell cycle; G1 phase arrest; and p53;
D O I
10.1006/bbrc.1997.7495
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Estrogen binds to two classes of proteins in the cells, the high-affinity estrogen receptor (ER) as well as a low affinity estrogen type II binding site (EBS-II). Methyl p-hydroxyphenyllactate (MeHPLA) is an endogenous ligand for EBS-II. Binding of MeHPLA to EBS-II has a growth regulatory effect in estrogen-responsive cells, and levels of MeHPLA are decreased in breast cancer due to degradation by a specific esterase. 2,6-bis((3,4-dihydroxyphenyl)-methylene) cyclohexanone (BDHPC) is an esterase-resistant analogue of MeHPLA which binds irreversibly to EBS-II and inhibits growth of breast cancer cells. In the present study, we analyzed the mechanism of growth inhibition by BDHPC. Treatment with BDHPC resulted in accumulation of cells in G1 phase and apoptosis. The G1 accumulation was not dependent on a functional p53 gene. The G1-specific growth inhibition by BDHPC was found to act synergistically with the G2/M-specific inhibition induced by the tyrosine kinase inhibitor genistein, suggesting this drug combination could be effectively used in cancer treatment. (C) 1997 Academic Press.
引用
收藏
页码:467 / 472
页数:6
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