Parabens are p-
hydroxybenzoic acid esters that have been used extensively as preservatives in foods,
cosmetics, drugs and toiletries. These intact
esters are commonly detected in human
breast cancer tissues and other human samples, thus arousing concern about the involvement of
parabens in human
breast cancer. In this study, an in vitro
nuclear receptor coactivator recruiting assay was developed and used to evaluate the binding activities of
parabens,
salicylates and
benzoates via antagonist competitive binding on the human oestrogen-related receptor γ (ERRγ), which is known as both a diagnostic
biomarker and a treatment target of
breast cancer. The results showed that all of the test
parabens (methyl-, ethyl-, propyl-, butyl- and
benzylparaben) possessed clear inverse antagonist activities on ERRγ, with a lowest observed effect level (LOEL) of 10(-7)M and the 50% relative effective concentrations (REC50) varying from 3.09×10(-7) to 5.88×10(-7)M, whereas the
salicylates possessed much lower activities and the
benzoates showed no obvious activity. In silico molecular docking analyses showed that
parabens fitted well into the active site of ERRγ, with hydrogen bonds forming between the p-
hydroxyl group of
parabens and the Glu275/Arg316 of ERRγ. As the
paraben levels reported in
breast cancer tissues are commonly higher than the LOELs observed in this study,
parabens may play some role via ERRγ in the
carcinogenesis of human
breast cancer. In addition,
parabens may have significant effects on
breast cancer patients who are taking
tamoxifen, as ERRγ is regarded as a treatment target for
tamoxifen.