Oestrogenic activity of parabens in MCF7 human breast cancer cells

被引:318
作者
Byford, JR
Shaw, LE
Drew, MGB
Pope, GS
Sauer, MJ
Darbre, PD [1 ]
机构
[1] Univ Reading, Sch Anim & Microbial Sci, Div Cell & Mol Biol, Reading RG6 6AJ, Berks, England
[2] Univ Reading, Dept Chem, Reading RG6 6AD, Berks, England
[3] Vet Labs Agcy, Addlestone KT15 3NB, Surrey, England
关键词
parabens; breast cancer cells; environmental oestrogen;
D O I
10.1016/S0960-0760(01)00174-1
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
Parabens (4-hydroxybenzoic acid esters) have been recently reported to have oestrogenic activity in yeast cells and animal models. Since the human population is exposed to parabens through their widespread use as preservatives in foods, pharmaceuticals and cosmetics, we have investigated here whether oestrogenic activity of these compounds can also be detected in oestrogen-sensitive human cells. We report on the oestrogenic effects of four parabens (methylparaben, ethylparaben. n-propylparaben, it-butylparaben) in oestrogen-dependent MCF7 human breast cancer cells, Competitive inhibition of [H-3]oestradiol binding to MCF7 cell oestrogen receptors could be detected at 1,000,000-fold molar excess of n-butylparaben (86%), n-propylparaben (77%). ethyl-paraben (54%) and methylparaben (21%). At concentrations of 10(-6) M and above, parabens were are able to increase expression of both transfected (ERE-CAT reporter gene) and endogenous (pS2) oestrogen-regulated genes in these cells. They could also increase proliferation of the cells in monolayer culture. which could be inhibited by the antiestrogen ICI 182,780, indicating that the effects were mediated through the oestrogen receptor. However, no antagonist activity of parabens could be detected on regulation of cell proliferation by 17beta-oestradiol at 10(-10) M. Molecular modelling has indicated the mode by which paraben molecules can bind into the ligand binding pocket of the crystal structure of the ligand binding domain (LBD) of the oestrogen receptor alpha (ERalpha) in place of 17beta-oestradiol: it has furthermore shown that two paraben molecules can bind simultaneously in a mode in which their phenolic hydroxyl groups bind similarly to those of the meso-hexoestrot molecule. Future work will need to address the extent to which parabens can accumulate in hormonally sensitive tissues and also the extent to which their weak oestrogenic activity can add to the more general environmental oestrogen problem. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:49 / 60
页数:12
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