Therapeutic significance of estrogen receptor β agonists in gliomas

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

Research output: Contribution to journalArticle

50 Citations (Scopus)

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 significantly reduced in vivo tumor growth in a xenograft model. Compared with control mice, animals treated with liquiritigenin had greater than 50% reduction in tumor volume and size. Immunohistochemical analysis of tumors revealed a significant increase in the nuclear ERβ expression with a concomitant decrease in cell proliferation in the liquiritigenin-treated group. Our results suggest that ERβ signaling has a tumor-suppressive function in gliomas. Because ERβ agonists are currently in clinical trials and are well tolerated with fewer side effects, identification of an ERβ agonist as a therapeutic agent can be readily extended to clinical use with current chemotherapies, providing an additional tool for enhancing survival in glioma patients.

Original languageEnglish (US)
Pages (from-to)1174-1182
Number of pages9
JournalMolecular cancer therapeutics
Volume11
Issue number5
DOIs
StatePublished - Jun 29 2012

Fingerprint

Glioma
Estrogen Receptors
Estrogens
Neoplasms
Therapeutics
Sexism
Phytoestrogens
Central Nervous System Neoplasms
Growth
Tumor Burden
Heterografts
Carcinogens
Down-Regulation
Cell Proliferation
Clinical Trials
Drug Therapy
Survival
liquiritigenin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Therapeutic significance of estrogen receptor β agonists in gliomas. / Sareddy, Gangadhara R.; Nair, Binoj C.; Gonugunta, Vijay K.; Zhang, Quanguang; Brenner, Andrew; Brann, Darrell W; Tekmal, Rajeshwar Rao; Vadlamudi, Ratna K.

In: Molecular cancer therapeutics, Vol. 11, No. 5, 29.06.2012, p. 1174-1182.

Research output: Contribution to journalArticle

Sareddy, GR, Nair, BC, Gonugunta, VK, Zhang, Q, Brenner, A, Brann, DW, Tekmal, RR & Vadlamudi, RK 2012, 'Therapeutic significance of estrogen receptor β agonists in gliomas', Molecular cancer therapeutics, vol. 11, no. 5, pp. 1174-1182. https://doi.org/10.1158/1535-7163.MCT-11-0960
Sareddy, Gangadhara R. ; Nair, Binoj C. ; Gonugunta, Vijay K. ; Zhang, Quanguang ; Brenner, Andrew ; Brann, Darrell W ; Tekmal, Rajeshwar Rao ; Vadlamudi, Ratna K. / Therapeutic significance of estrogen receptor β agonists in gliomas. In: Molecular cancer therapeutics. 2012 ; Vol. 11, No. 5. pp. 1174-1182.
@article{4067dbf365c6448e82041448eebeadc3,
title = "Therapeutic significance of estrogen receptor β agonists in gliomas",
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 significantly reduced in vivo tumor growth in a xenograft model. Compared with control mice, animals treated with liquiritigenin had greater than 50{\%} reduction in tumor volume and size. Immunohistochemical analysis of tumors revealed a significant increase in the nuclear ERβ expression with a concomitant decrease in cell proliferation in the liquiritigenin-treated group. Our results suggest that ERβ signaling has a tumor-suppressive function in gliomas. Because ERβ agonists are currently in clinical trials and are well tolerated with fewer side effects, identification of an ERβ agonist as a therapeutic agent can be readily extended to clinical use with current chemotherapies, providing an additional tool for enhancing survival in glioma patients.",
author = "Sareddy, {Gangadhara R.} and Nair, {Binoj C.} and Gonugunta, {Vijay K.} and Quanguang Zhang and Andrew Brenner and Brann, {Darrell W} and Tekmal, {Rajeshwar Rao} and Vadlamudi, {Ratna K.}",
year = "2012",
month = "6",
day = "29",
doi = "10.1158/1535-7163.MCT-11-0960",
language = "English (US)",
volume = "11",
pages = "1174--1182",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Therapeutic significance of estrogen receptor β agonists in gliomas

AU - Sareddy, Gangadhara R.

AU - Nair, Binoj C.

AU - Gonugunta, Vijay K.

AU - Zhang, Quanguang

AU - Brenner, Andrew

AU - Brann, Darrell W

AU - Tekmal, Rajeshwar Rao

AU - Vadlamudi, Ratna K.

PY - 2012/6/29

Y1 - 2012/6/29

N2 - 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 significantly reduced in vivo tumor growth in a xenograft model. Compared with control mice, animals treated with liquiritigenin had greater than 50% reduction in tumor volume and size. Immunohistochemical analysis of tumors revealed a significant increase in the nuclear ERβ expression with a concomitant decrease in cell proliferation in the liquiritigenin-treated group. Our results suggest that ERβ signaling has a tumor-suppressive function in gliomas. Because ERβ agonists are currently in clinical trials and are well tolerated with fewer side effects, identification of an ERβ agonist as a therapeutic agent can be readily extended to clinical use with current chemotherapies, providing an additional tool for enhancing survival in glioma patients.

AB - 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 significantly reduced in vivo tumor growth in a xenograft model. Compared with control mice, animals treated with liquiritigenin had greater than 50% reduction in tumor volume and size. Immunohistochemical analysis of tumors revealed a significant increase in the nuclear ERβ expression with a concomitant decrease in cell proliferation in the liquiritigenin-treated group. Our results suggest that ERβ signaling has a tumor-suppressive function in gliomas. Because ERβ agonists are currently in clinical trials and are well tolerated with fewer side effects, identification of an ERβ agonist as a therapeutic agent can be readily extended to clinical use with current chemotherapies, providing an additional tool for enhancing survival in glioma patients.

UR - http://www.scopus.com/inward/record.url?scp=84862751553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862751553&partnerID=8YFLogxK

U2 - 10.1158/1535-7163.MCT-11-0960

DO - 10.1158/1535-7163.MCT-11-0960

M3 - Article

VL - 11

SP - 1174

EP - 1182

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 5

ER -