Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation

Phytother Res. 2014 Oct;28(10):1553-60. doi: 10.1002/ptr.5167. Epub 2014 May 15.

Abstract

Breast cancer is the most common cancer in women. Bisphenol A (BPA), as a known endocrine disrupter, is closely related to the development of breast cancer. Curcumin has been clinically used in chemopreventation and treatment of cancer; however, it remains unknown whether microRNAs are involved in curcumin-mediated protection from BPA-associated promotive effects on breast cancer. In the present study, we showed that BPA exhibited estrogenic activity by increasing the proliferation of estrogen-receptor-positive MCF-7 human breast cancer cells and triggering transition of the cells from G1 to S phase. Curcumin inhibited the proliferative effects of BPA on MCF-7 cells. Meanwhile, BPA-induced upregulation of oncogenic miR-19a and miR-19b, and the dysregulated expression of miR-19-related downstream proteins, including PTEN, p-AKT, p-MDM2, p53, and proliferating cell nuclear antigen, were reversed by curcumin. Furthermore, the important role of miR-19 in BPA-mediated MCF-7 cell proliferation was also illustrated. These results suggest for the first time that curcumin modulates miR-19/PTEN/AKT/p53 axis to exhibit its protective effects against BPA-associated breast cancer promotion. Findings from this study could provide new insights into the molecular mechanisms by which BPA exerts its breast-cancer-promoting effect as well as its target intervention.

Keywords: MCF-7 breast cancer cells; bisphenol A; curcumin; inhibition; miR-19; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds
  • Breast Neoplasms / metabolism
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology*
  • Female
  • Humans
  • MCF-7 Cells
  • MicroRNAs / metabolism*
  • PTEN Phosphohydrolase / metabolism*
  • Phenols
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Benzhydryl Compounds
  • MIRN19 microRNA, human
  • MicroRNAs
  • Phenols
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Curcumin
  • bisphenol A