title: Exposure to parabens at the concentration of maximal proliferative response increases migratory and invasive activity of human breast cancer cells in vitro.
abstract: Alkyl esters of p-hydroxybenzoic acid (parabens) are widely used as preservatives in personal care products, foods and pharmaceuticals. Their oestrogenic activity, their measurement in human breast tissue and their ability to drive proliferation of oestrogen-responsive human breast cancer cells has opened a debate on their potential to influence breast cancer development. As proliferation is not the only hallmark of cancer cells, we have investigated the effects of exposure to parabens at concentrations of maximal proliferative response on migratory and invasive properties using three oestrogen-responsive human breast cancer cell lines (MCF-7, T-47-D, ZR-75-1). Cells were maintained short-term (1 week) or long-term (20 ± 2 weeks) in phenol-red-free medium containing 5% charcoal-stripped serum with no addition, 10(-8)  M 17β-oestradiol, 1-5 × 10(-4)  M methylparaben, 10(-5)  M n-propylparaben or 10(-5)  M n-butylparaben. Long-term exposure (20 ± 2 weeks) of MCF-7 cells to methylparaben, n-propylparaben or n-butylparaben increased migration as measured using a scratch assay, time-lapse microscopy and xCELLigence technology: invasive properties were found to increase in matrix degradation assays and migration through matrigel on xCELLigence. Western immunoblotting showed an associated downregulation of E-cadherin and β-catenin in the long-term paraben-exposed cells which could be consistent with a mechanism involving epithelial to mesenchymal transition. Increased migratory activity was demonstrated also in long-term paraben-exposed T-47-D and ZR-75-1 cells using a scratch assay and time-lapse microscopy. This is the first report that in vitro, parabens can influence not only proliferation but also migratory and invasive properties of human breast cancer cells.
authors.affiliation: School of Biological Sciences, University of Reading, Reading, RG6 6UB, UK.
authors.forename: Sugandha
authors.initials: S
authors.lastname: Khanna
authors.forename: Philip R
authors.initials: PR
authors.lastname: Dash
authors.forename: Philippa D
authors.initials: PD
authors.lastname: Darbre
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D010226:Parabens / Q000633:toxicity*; D011310:Preservatives, Pharmaceutical / Q000633:toxicity; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D004967:Estrogens; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D051176:beta Catenin; C038091:butylparaben; D004958:Estradiol; C015358:methylparaben; C006068:propylparaben
keywords: breast cancer; invasion; metastasis; migration; motility; paraben; xenoestrogen