A New Class of Estrogen Receptor Beta-Selective Activators

Lo, Raymond; Matthews, Jason

doi:10.1124/mi.10.3.3

Cited by 21 publications

(17 citation statements)

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“…Currently, various ERβ-selective drugs including DPN, ERB-041, MF101, liquiritigenin are being investigated as a replacement for estrogens to treat menopausal symptoms (17, 18). Previous studies showed that ERβ agonist such as liquiritigenin did not stimulate tumor growth of breast cancer cells in nude mice studies, suggesting the lack of proliferative actions of liquiritigenin (26).…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic Significance of Estrogen Receptor β Agonists in Gliomas

Sareddy

Nair

Gonugunta

et al. 2012

Molecular Cancer Therapeutics

133

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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 ER subtypes: ERα, that functions as tumor promoter and ERβ that function 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. IHC analysis of tumor tissues revealed that ERβ expression is down regulated 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 to control mice, animals treated with liquiritigenin had greater than 50% reduction in tumor volume and size. IHC 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. Since 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.

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Section: Discussionmentioning

confidence: 99%

“…Eventhough ERα and ERβ are structurally similar, their ligand-binding domains differ enough to be selective for different ligands (17). Recent studies have shown that ERβ has quite a different function than ERα (18) and is generally considered a tumor suppressor.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Significance of Estrogen Receptor β Agonists in Gliomas

Sareddy

Nair

Gonugunta

et al. 2012

Molecular Cancer Therapeutics

133

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“…Because ER α and ER β have different physiological functions and have ligand-binding properties that differ enough to be selective in their ligand binding, opportunities now exist for testing of novel ER subtype-specific, selective ER modulators [77]. Several synthetic or novel natural compounds derived from plant materials have the potential to function as ER β agonists [54, 78], and these compounds may have utility in augmenting ER β tumor suppressive functions.…”

Section: Therapeutic Targeting Of Erα Signaling For Blocking Metamentioning

confidence: 99%

Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

Roy

Vadlamudi

2012

International Journal of Breast Cancer

171

116

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Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis.

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“…A large variety of ERb specific agonists have been reported in the literature although not all have been neurologically tested (Lo and Matthews, 2010;Mohler et al, 2010). Some of these include caffeic acid phenethyl ester (Jung et al, 2010), butyl 4-(butyryloxy) benzoate (Lin et al, 2008), the diarylpropionitriles (Meyers et al, 2001), the aryl diphenolic azoles and the benzoazole ERB-041 (Malamas et al, 2004;Follettie et al, 2006), genistein derivatives (Mewshaw et al, 2005), effusol derivatives (e.g., benzo[c]chromenone analogs) (Sun et al, 2006), salicylaldoximes (Bertini et al, 2011) and the tetrahydrofluorenones (Parker et al, 2006;Wilkening et al, 2006).…”

Section: Introductionmentioning

confidence: 99%