2018
DOI: 10.1093/toxsci/kfy063
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Metabolites of n-Butylparaben and iso-Butylparaben Exhibit Estrogenic Properties in MCF-7 and T47D Human Breast Cancer Cell Lines

Abstract: Two oxidized metabolites of n-butylparaben (BuP) and iso-butylparaben (IsoBuP) discovered in human urine samples exhibit structural similarity to endogenous estrogens. We hypothesized that these metabolites bind to the human estrogen receptor (ER) and promote estrogen signaling. We tested this using models of ER-mediated cellular proliferation. The estrogenic properties of 3-hydroxy n-butyl 4-hydroxybenzoate (3OH) and 2-hydroxy iso-butyl 4-hydroxybenzoate (2OH) were determined using the ER-positive, estrogen-d… Show more

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Cited by 20 publications
(12 citation statements)
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“…These results are in agreement with in vitro data regarding the ability of these compounds to bind to mammalian estrogen receptors and modulate estrogen signaling pathways [3, 5, 28, 47, 53, 125]. Moreover, our detailed comparisons of docking results consistently revealed high similarity between human and rodent ligand-receptor complexes in support of our working hypothesis and indicating that the interspecies sequence differences in these receptors could be regarded as neutral substitutions.…”
Section: Discussionsupporting
confidence: 90%
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“…These results are in agreement with in vitro data regarding the ability of these compounds to bind to mammalian estrogen receptors and modulate estrogen signaling pathways [3, 5, 28, 47, 53, 125]. Moreover, our detailed comparisons of docking results consistently revealed high similarity between human and rodent ligand-receptor complexes in support of our working hypothesis and indicating that the interspecies sequence differences in these receptors could be regarded as neutral substitutions.…”
Section: Discussionsupporting
confidence: 90%
“…In this connection, the identification and characterization of suspected endocrine disrupting compounds EDCs using both in vitro and in vivo methods has been considered a major subject of toxicology research for several decades [94]. Furthermore, parabens represent one category of suspected EDCs that have been investigated for their potential action on ERα and related hormone signaling pathways [28, 47]. Although paraben compounds are generally considered weak agonists of ERα, they are still being investigated to determine whether current exposures may lead to adverse impacts on human health [24, 27, 95].…”
Section: Discussionmentioning
confidence: 99%
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“…Differences in concentrations of methyl and propyl paraben biomarkers were among the highest observed in this study, particularly for the youngest non-Hispanic Black women. These chemicals have been used as preservatives in personal care products, pharmaceuticals, and food additives, and have been found to promote cell growth through multiple mechanisms, including estrogenicity (Gonzalez et al 2018, 2019; Okubo et al 2001) and epidermal growth factor receptor signaling (Pan et al 2016). Particularly relevant to our findings of the greatest methyl and ethyl paraben disparities in the youngest non-Hispanic Black women was the finding that early life paraben exposures can alter developing mammary gland morphology and induce gene expression that resembles an early cancer-like state (Gopalakrishnan et al 2017).…”
Section: Discussionmentioning
confidence: 99%
“…The widespread use of parabens in PCPs has led to research studies to determine the extent of human exposure and investigate whether there is evidence for endocrine disrupting behavior (Witorsch and Thomas, 2010). In vitro studies have shown that parabens exhibit weak estrogenic behavior, bind to ERα to promote ER-dependent gene transcription, and induce increased cellular proliferation of ERdependent breast cancer cells (Delfosse et al, 2014;Gonzalez et al, 2018;Watanabe et al, 2013;Wielogorska et al, 2015;Wrobel and Gregoraszczuk, 2014). Evidence of estrogenic behavior for n-butylparaben in vivo was observed when Hu et al treated immature Sprague Dawley rats at a dose of 0.16 mg/kg/day for three days via intragastric administration (Hu et al, 2013).…”
Section: Parabensmentioning
confidence: 99%