Modulation of Estrogen α and Progesterone Receptors in Triple Negative Breast Cancer Cell Lines: The Effects of Vorinostat and Indole-3-Carbinol In Vitro

Anticancer Res. 2020 Jul;40(7):3669-3683. doi: 10.21873/anticanres.14356.

Abstract

Background/aim: Triple negative cancer (TNBC) is a subtype of breast cancer that is highly aggressive, with poor prognosis and responds differently to treatments. This study investigated the role of vorinostat and indole-3-carbinol (I3C) on regulating critical receptors that are not normally expressed in TNBC.

Materials and methods: Using real-time PCR, immunostaining, and western blots, the re-expression of estrogen receptor α (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) receptors was examined in four different TNBC cell types.

Results: ERα was re-expressed in three subtypes using vorinostat and I3C. Re-expression of the PR by vorinostat was also detected. Neither vorinostat nor I3C resulted in re-expression of the HER2 receptor. A significant decrease in growth and sensitivity to tamoxifen was also noted.

Conclusion: The results of this study show that vorinostat and I3C modulate the re-expression of critical receptors in certain subtypes of TNBC through several pathways and these effects can be influenced by the molecular profiles of TNBCs.

Keywords: HDAC activity; HDAC7; I3C; Vorinostat; estrogen receptor; progesterone receptor; triple negative breast cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Indoles / pharmacology*
  • MCF-7 Cells
  • Receptor, ErbB-2 / metabolism
  • Receptors, Progesterone / metabolism*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism*
  • Vorinostat / pharmacology*

Substances

  • Antineoplastic Agents
  • Estrogen Receptor alpha
  • Indoles
  • Receptors, Progesterone
  • Vorinostat
  • indole-3-carbinol
  • Receptor, ErbB-2