The phytoestrogen genistein affects inflammatory-related genes expression depending on the ERα/ERβ ratio in breast cancer cells

Abstract

Breast cancer is the most common malignancy in women of developed countries. The aim of this study was to investigate the effects of the phytoestrogen genistein on the inflammatory profile in three breast cancer cell lines with different oestrogen receptors alpha (ERα) and beta (ERβ) ratio. MCF-7 (high ERα/ERβ ratio), T47D (low ERα/ERβ ratio), and MDA-MB-231 (ERα-negative) cells were treated with 1 µM of genistein for 48 h (cell proliferation and ROS production) or 4 h (mRNA expression of 18S, ERα, ERβ, pS2, Sirtuin1, IL-1β, NF-κB, COX-2, TGFβ1, PPARγ). Genistein caused a significant decrease in cell viability and an increase in ROS production in MCF-7, and the opposite happens in T47D cells. In addition, genistein rise pro-inflammatory and reduced anti-inflammatory genes expression in MCF-7, provoking the opposite effects in T47D cells. In conclusion, the phytoestrogen genistein could modulate the expression of inflammatory-related genes through its interaction with both ERs, and its effects depends on the ERα/ERβ ratio.

Keywords: Breast cancer; ERα/ERβ ratio; genistein; inflammation; sirtuin.