Therapeutic Significance of Estrogen Receptor β Agonists in Gliomas

Gangadhara R. Sareddy,Binoj C. Nair,Vijay K. Gonugunta,Quan-guang Zhang,Andrew Brenner,Darrell W. Brann,Rajeshwar Rao Tekmal, and Ratna K. Vadlamudi

Abstract

Gliomas are the most common and devastating central nervous system neoplasms. A gender bias exists in their development: females are at lower risk than males, implicating estrogen-mediated protective effects. Estrogen functions are mediated by two estrogen receptor (ER) subtypes: ERα, which functions as tumor promoter, and ERβ, which functions as tumor suppressor. We examined the potential use of ERβ agonists as a novel therapeutic to curb the growth of gliomas. Western analysis of six glioma model cells showed detectable expression of ERβ with little or no ERα. Treatment of glioma cells with ERβ agonists resulted in significant decrease in proliferation. Immunohistochemical analysis of tumor tissues revealed that ERβ expression is downregulated in high-grade gliomas. We found that ERβ agonists promote both expression and tumor-suppressive functions of ERβ in glioma cells. Liquiritigenin, a plant-derived ERβ agonist

 Liquiritigenin was purchased from Biopurify Phytochemicals.