Effects of single and repeated in vitro exposure of three forms of parabens, methyl-, butyl- and propylparabens on the proliferation and estradiol secretion in MCF-7 and MCF-10A cells

Pharmacol Rep. 2013;65(2):484-93. doi: 10.1016/s1734-1140(13)71024-7.

Abstract

Background: Here, we analyzed the dose- (0.2, 2, 20, 200 nM or 2 μM) and time- (48, 96, 144 and 196 h) dependent activity of a single or repeated exposure of methyl-, butyl- and propylparaben on the proliferation of MCF-7 human breast cancer cells and MCF-10A human breast epithelial cells. Additionally, the effect on estradiol secretion, gene and protein expression of aromatase (CYP19A1) was investigated.

Methods: Cell proliferation was determined by AlamarBlue assay, and estradiol secretion by ELISA kits. Gene and protein expression of CYP19A1 was measurement using real time PCR and western blot, respectively.

Results: Stimulatory effect of a single exposure of all doses of tested parabens and time dependent effect of repeated exposure to methylparaben, propylparaben and butylparaben, the same as that of 17β-estradiol, on proliferation of MCF-7 cells was observed. Only at low doses methyl- and butylparabens increased MCF-10A cells proliferation after single exposure, but no effect of repeated exposure was noted. Exposure at low doses of all of the parabens significantly increased 17β-estradiol (E2) secretion in MCF-7 cells but had the opposite effect on MCF-10A cells. It was correlated with gene and protein expression of CYP19A1 in MCF-7 and MCF-10 cells.

Conclusions: In summary, present study indicates a different mechanism of proliferative action of parabens in investigated cell lines. In MCF-7 breast cancer cell line it is probably due to stimulatory action on estradiol secretion and aromatase activity. In MCF-10A by an unknown mechanism, independent on stimulatory action on estradiol section, which requires further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aromatase / genetics
  • Blotting, Western
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Estradiol / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • MCF-7 Cells
  • Parabens / administration & dosage
  • Parabens / pharmacology*
  • Real-Time Polymerase Chain Reaction
  • Time Factors

Substances

  • Parabens
  • butylparaben
  • Estradiol
  • methylparaben
  • Aromatase
  • CYP19A1 protein, human
  • propylparaben