Design, Synthesis, and Estrogenic Activity of a Novel Estrogen Receptor ModulatorA Hybrid Structure of 17β-Estradiol and Vitamin E in Hippocampal Neurons

2007 ◽  
Vol 50 (18) ◽  
pp. 4471-4481 ◽  
Author(s):  
Liqin Zhao ◽  
Chunyang Jin ◽  
Zisu Mao ◽  
Madathil B. Gopinathan ◽  
Kenneth Rehder ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Vitamin E ◽  
Hippocampal Neurons ◽  
Estrogenic Activity ◽  
Hybrid Structure ◽  
Design Synthesis ◽  
17Β Estradiol

Phytoestrogens Induce Differential Estrogen Receptor Alpha- or Beta-Mediated Responses in Transfected Breast Cancer Cells

2005 ◽  
Vol 230 (8) ◽  
pp. 558-568 ◽  
Author(s):  
D. M. Harris ◽  
E. Besselink ◽  
S. M. Henning ◽  
V. L. W. Go ◽  
D. Heber
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Estrogenic Activity ◽  
Mammary Adenocarcinoma ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Human Estrogen Receptor ◽  
17Β Estradiol ◽  
Risk Of Cancer

Increased intake of phytoestrogens may be associated with a lower risk of cancer in the breast and several other sites, although there is controversy surrounding this activity. One of the mechanisms proposed to explain the activity of phytoestrogens is their ability to bind and activate human estrogen receptor a (ERα) and human estrogen receptor β (ERβ). Nine phytoestrogens were tested for their ability to transactivate ERα or ERβ at a range of doses. Mammary adenocarcinoma (MCF-7) cells were co-transfected with either ERα or ERβ, and an estrogen-response element was linked to a luciferase reporter gene. Dose-dependent responses were compared with the endogenous ligand 17β-estradiol. Purified genistein, daidzein, apigenin, and coumestrol showed differential and robust transactivation of ERα- and ERβ-induced transcription, with an up to 100-fold stronger activation of ERβ. Equol, naringenin, and kaempferol were weaker agonists. When activity was evaluated against a background of 0.5 nM 17β-estradiol, the addition of genistein, daidzein, and resveratrol superstimulated the system, while kaempferol and quercetin were antagonists at the highest doses. This transfection assay provides an excellent model to evaluate the activation of ERα and ERβ by different phytoestrogens in a breast cancer context and can be used as a screening bioassay tool to evaluate the estrogenic activity of extracts of herbs and foods.

scholarly journals Ginsenoside-Rb1 from Panax ginseng C.A. Meyer Activates Estrogen Receptor-α and -β, Independent of Ligand Binding

2004 ◽  
Vol 89 (7) ◽  
pp. 3510-3515 ◽  
Author(s):  
JungYoon Cho ◽  
Wankyu Park ◽  
SeungKi Lee ◽  
Woongshick Ahn ◽  
YoungJoo Lee
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Estrogen Receptors ◽  
Panax Ginseng ◽  
Estrogenic Activity ◽  
Specific Binding ◽  
Dependent Manner ◽  
Ginsenoside Rb1 ◽  
17Β Estradiol ◽  
Mcf 7

Abstract We studied the estrogenic activity of a component of Panax ginseng, ginsenoside-Rb1. The activity of ginsenoside-Rb1 was characterized in a transient transfection system, using estrogen receptor isoforms and estrogen-responsive luciferase plasmids, in COS monkey kidney cells. Ginsenoside-Rb1 activated both α and β estrogen receptors in a dose-dependent manner with maximal activity observed at 100 μm, the highest concentration examined. Activation was inhibited by the estrogen receptor antagonist ICI 182,780, indicating that the effects were mediated through the estrogen receptor. Treatment with 17β-estradiol or ginsenoside-Rb1 increased expression of the progesterone receptor, pS2, and estrogen receptor in MCF-7 cells and of AP-1-driven luciferase genes in COS cells. Although these data suggest that it is functionally very similar to 17β-estradiol, ginsenoside-Rb1 failed to displace specific binding of [3H]17β-estradiol from estrogen receptors in MCF-7 whole-cell ligand binding assays. Our results indicate that the estrogen-like activity of ginsenoside-Rb1 is independent of direct estrogen receptor association.

G protein-coupled estrogen receptor is required for the neuritogenic mechanism of 17β-estradiol in developing hippocampal neurons

2013 ◽  
Vol 372 (1-2) ◽  
pp. 105-115 ◽  
Author(s):  
Isabel Ruiz-Palmero ◽  
Maria Hernando ◽  
Luis M. Garcia-Segura ◽  
Maria-Angeles Arevalo
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Hippocampal Neurons ◽  
17Β Estradiol ◽  
G Protein Coupled

scholarly journals In vitro Gender Differences in Neuronal Survival on Hypoxia and in 17β-Estradiol-Mediated Neuroprotection

2005 ◽  
Vol 25 (4) ◽  
pp. 427-430 ◽  
Author(s):  
Andrea Heyer ◽  
Martin Hasselblatt ◽  
Nicolas von Ahsen ◽  
Heinz Häfner ◽  
Anna-Leena Sirén ◽  
...  
Keyword(s):  
Gender Differences ◽  
Estrogen Receptor ◽  
Hippocampal Neurons ◽  
Estrogen Receptor Beta ◽  
Membrane Receptors ◽  
Pronounced Increase ◽  
Neuropsychiatric Disease ◽  
17Β Estradiol ◽  
Receptor Beta

Gender differences in neuropsychiatric disease are recognized but not well understood. Investigating the survival of primary rat hippocampal neurons in culture, we found significant and inverted gender differences on normoxia versus hypoxia. Male cells were more resistant under normoxia but more vulnerable under hypoxia than female cells. Male vulnerability pattern was acquired in cells from neonatally testosterone-primed females. Estrogens, acting via membrane receptors, had a higher neuroprotective power in male neurons, explained at least in part by the pronounced increase in estrogen receptor beta/alpha ratio during hypoxia in male cells only.

scholarly journals A New Anti-Estrogen Discovery Platform Identifies FDA-Approved Imidazole Anti-Fungal Drugs as Bioactive Compounds against ERα Expressing Breast Cancer Cells

2021 ◽  
Vol 22 (6) ◽  
pp. 2915
Author(s):  
Manuela Cipolletti ◽  
Stefania Bartoloni ◽  
Claudia Busonero ◽  
Martina Parente ◽  
Stefano Leone ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bioactive Compounds ◽  
Estrogenic Activity ◽  
Estrogen Receptor Α ◽  
Breast Cancers ◽  
Cellular Models ◽  
Cancer Models ◽  
17Β Estradiol ◽  
Approved Drugs ◽  
Anti Fungal

17β-estradiol (E2) exerts its physiological effects through the estrogen receptor α (i.e., ERα). The E2:ERα signaling allows the regulation of cell proliferation. Indeed, E2 sustains the progression of ERα positive (ERα+) breast cancers (BCs). The presence of ERα at the BC diagnosis drives their therapeutic treatment with the endocrine therapy (ET), which restrains BC progression. Nonetheless, many patients develop metastatic BCs (MBC) for which a treatment is not available. Consequently, the actual challenge is to complement the drugs available to fight ERα+ primary and MBC. Here we exploited a novel anti-estrogen discovery platform to identify new Food and Drug Administration (FDA)-approved drugs inhibiting E2:ERα signaling to cell proliferation in cellular models of primary and MBC cells. We report that the anti-fungal drugs clotrimazole (Clo) and fenticonazole (Fenti) induce ERα degradation and prevent ERα transcriptional signaling and proliferation in cells modeling primary and metastatic BC. The anti-proliferative effects of Clo and Fenti occur also in 3D cancer models (i.e., tumor spheroids) and in a synergic manner with the CDK4/CDK6 inhibitors palbociclib and abemaciclib. Therefore, Clo and Fenti behave as “anti-estrogens”-like drugs. Remarkably, the present “anti-estrogen” discovery platform represents a valuable method to rapidly identify bioactive compounds with anti-estrogenic activity.

scholarly journals PARP7 and Mono-ADP-Ribosylation Negatively Regulate Estrogen Receptor α Signaling in Human Breast Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 623
Author(s):  
Marit Rasmussen ◽  
Susanna Tan ◽  
Venkata S. Somisetty ◽  
David Hutin ◽  
Ninni Elise Olafsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Protein Modification ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
Transactivation Domain ◽  
Adp Ribosylation ◽  
Protein Levels ◽  
17Β Estradiol ◽  
Mcf 7

ADP-ribosylation is a post-translational protein modification catalyzed by a family of proteins known as poly-ADP-ribose polymerases. PARP7 (TIPARP; ARTD14) is a mono-ADP-ribosyltransferase involved in several cellular processes, including responses to hypoxia, innate immunity and regulation of nuclear receptors. Since previous studies suggested that PARP7 was regulated by 17β-estradiol, we investigated whether PARP7 regulates estrogen receptor α signaling. We confirmed the 17β-estradiol-dependent increases of PARP7 mRNA and protein levels in MCF-7 cells, and observed recruitment of estrogen receptor α to the promoter of PARP7. Overexpression of PARP7 decreased ligand-dependent estrogen receptor α signaling, while treatment of PARP7 knockout MCF-7 cells with 17β-estradiol resulted in increased expression of and recruitment to estrogen receptor α target genes, in addition to increased proliferation. Co-immunoprecipitation assays revealed that PARP7 mono-ADP-ribosylated estrogen receptor α, and mass spectrometry mapped the modified peptides to the receptor’s ligand-independent transactivation domain. Co-immunoprecipitation with truncated estrogen receptor α variants identified that the hinge region of the receptor is required for PARP7-dependent mono-ADP-ribosylation. These results imply that PARP7-mediated mono-ADP-ribosylation may play an important role in estrogen receptor positive breast cancer.

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