Lack of Significant Estrogenic or Antiestrogenic Activity of Pyrethroid Insecticides in Three in Vitro Assays Based on Classic Estrogen Receptor alpha-Mediated Mechanisms

Employing ensemble Protein-Ligand Interaction Fingerprints (ensPLIF) as descriptors in post retrospective Structure-Based Virtual Screening (SBVS) campaigns Quantitative Structure-Activity Relationship (QSAR) analysis has been proven to significantly increase the predictive ability in the identification of potent ligands for estrogen receptor alpha (ERα). In the research presented in this article, similar approaches have been performed to construct and retrospectively validate an SBVS protocol to identify marginal ligands for ERα. Based on both validated SBVS protocols, a graphical-user-interface (GUI) application to identify if a compound is a non-, moderate or potent ligand for ERα was developed. The GUI application was subsequently used to virtually screen genistin, genistein, daidzin, and daidzein, followed by in vitro test employing a cytotoxic assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method.

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MP68-13 ESTROGEN RECEPTOR ALPHA PREVENTS BLADDER CANCER VIA INPP4B INHIBITED AKT PATHWAY IN VITRO AND IN VIVO

The Journal of Urology ◽

10.1016/j.juro.2015.02.2475 ◽

2015 ◽

Vol 193 (4S) ◽

Author(s):

Chiuan-Ren Yeh ◽

Iawen Hsu ◽

Hiroshi Miyamoto ◽

Xue-Ru Wu ◽

Chawnshang Chang ◽

...

Keyword(s):

Bladder Cancer ◽

Estrogen Receptor ◽

Estrogen Receptor Alpha ◽

Akt Pathway ◽

Receptor Alpha

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Estrogen receptor-alpha-interacting cytokeratins potentiate the antiestrogenic activity of fulvestrant

Cancer Biology & Therapy ◽

10.4161/cbt.9.5.10926 ◽

2010 ◽

Vol 9 (5) ◽

pp. 389-396 ◽

Cited By ~ 5

Author(s):

Xinghua Long ◽

Meiyun Fan ◽

Kenneth P. Nephew

Keyword(s):

Estrogen Receptor ◽

Estrogen Receptor Alpha ◽

Receptor Alpha ◽

Antiestrogenic Activity

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Antiestrogenic activity of flavonoid phytochemicals mediated via the c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2012.05.004 ◽

2012 ◽

Vol 132 (1-2) ◽

pp. 186-193 ◽

Cited By ~ 13

Author(s):

Bridgette M. Collins-Burow ◽

James W. Antoon ◽

Daniel E. Frigo ◽

Steven Elliott ◽

Christopher B. Weldon ◽

...

Keyword(s):

Estrogen Receptor ◽

Protein Kinase ◽

Estrogen Receptor Alpha ◽

Cell Type ◽

Terminal Protein ◽

Receptor Alpha ◽

Antiestrogenic Activity ◽

Cell Type Specific ◽

Specific Regulation ◽

Kinase Pathway

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Computer-Aided Drug Repurposing: A Cyclooxygenase-2 Inhibitor Celecoxib as a Ligand for Estrogen Receptor Alpha

Indonesian Journal of Chemistry ◽

10.22146/ijc.21196 ◽

2015 ◽

Vol 15 (3) ◽

pp. 274-280 ◽

Cited By ~ 3

Author(s):

Enade Perdana Istyastono ◽

Florentinus Dika Octa Riswanto ◽

Sri Hartati Yuliani

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

In Silico ◽

Estrogen Receptor Alpha ◽

Cyclooxygenase 2 ◽

Cytotoxic Activities ◽

In Vitro Test ◽

Receptor Alpha ◽

Vitro Test

A cyclooxygenase-2 (COX-2) inhibitor celecoxib has been previously reported to have cytotoxic activities towards gastric, prostate, ovarian, colon and breast cancer cell lines. This article reports that the cytotoxic activities of celecoxib could be resulted from its activity as a potent ligand for estrogen receptor alpha (ERα). Aided by molecular docking simulations, an in silico test to examine whether celecoxib is a ligand for estrogen receptor alpha (ERα) was performed followed by in vitro test employing cytotoxic assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. The compound was extracted from Celebrex®. Measured by using UV spectrophotometric method at 255.5 nm, it was identified that the content of celecoxib was 102.15 mg/271.48 mg capsule content. The in silico test indicated that celecoxib is a potent ligand for ERα. This finding was confirmed experimentally by an in vitro test that celecoxib has a comparable activity as an ERα ligand to tamoxifen, a drug of choice for breast cancer treatment.

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Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications

Physiological Reviews ◽

10.1152/physrev.00024.2016 ◽

2017 ◽

Vol 97 (3) ◽

pp. 1045-1087 ◽

Cited By ~ 122

Author(s):

Jean-Francois Arnal ◽

Françoise Lenfant ◽

Raphaël Metivier ◽

Gilles Flouriot ◽

Daniel Henrion ◽

...

Keyword(s):

Estrogen Receptor ◽

Estrogen Receptor Alpha ◽

Reproductive Tract ◽

Vascular System ◽

Physiological Role ◽

Receptor Alpha ◽

Nuclear Signaling ◽

Nuclear Estrogen Receptor

Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.

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