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

2015 ◽  
Vol 15 (3) ◽  
pp. 274-280 ◽  
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.

scholarly journals Development of a Graphical User Interface Application to Identify Marginal and Potent Ligands for Estrogen Receptor Alpha

2019 ◽  
Vol 19 (2) ◽  
pp. 531 ◽  
Author(s):  
Nunung Yuniarti ◽  
Sudi Mungkasi ◽  
Sri Hartati Yuliani ◽  
Enade Perdana Istyastono
Keyword(s):  
Estrogen Receptor ◽  
User Interface ◽  
Graphical User Interface ◽  
Estrogen Receptor Alpha ◽  
Predictive Ability ◽  
In Vitro Test ◽  
Ligand Interaction ◽  
Qsar Analysis ◽  
Receptor Alpha

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.

In silico Molecular Modelling of Selected Natural Ligands and their Binding Features with Estrogen Receptor Alpha

2018 ◽  
Vol 15 (1) ◽  
pp. 89-96 ◽  
Author(s):  
V.L. Maruthanila ◽  
R. Elancheran ◽  
Nand Kishor Roy ◽  
Anupam Bhattacharya ◽  
Ajaikumar B. Kunnumakkara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Line ◽  
In Silico ◽  
Estrogen Receptor Alpha ◽  
Natural Compounds ◽  
Pharmacokinetic Parameters ◽  
Anticancer Activities ◽  
Receptor Alpha ◽  
Mcf 7

Background: Breast cancer is one of the most common cancers diagnosed among women. It is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha (ER&#945;) correlates with better prognosis and the likelihood of response to hormonal therapy. ER&#945; is an attractive target for the treatment of breast cancer. Most of the drugs currently used for the breast cancer treatment have numerous side effects and they are often unsuccessful in removing the tumour completely. Hence, we focused on natural compounds like flavonoids, polyphenols, etc. which do not exhibit any high toxic effects against normal cells. </P><P> Objectives: To identify the potential natural inhibitors for BCa through an optimised in silico approach. </P><P> Methods: Structural modification and molecular docking-based screening approaches were imposed to identify the novel natural compounds by using Schrödinger (Maestro 9.5). The Qikprop v3.5 was used for the evaluation of important ADME parameters and its permissible ranges. Cytotoxicity of the compounds was evaluated by MTT assay against MCF-7 Cell lines. Results: From the docking studies, we found that the compounds, Myricetin, Quercetin, Apigenin, Luteolin and Baicalein showed the highest Glide Scores -10.78, -9.48, -8.92, -8.87 and -8.82 kcal mol-1 respectively. Of these, Luteolin and Baicalein showed the significant IC50 values (25 &#177; 4.0 and 58.3 &#177; 4.4 &#181;M, respectively) against MCF-7 cell line. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. We mainly focused on in silico study to dock the compounds into the human estrogen receptor ligand binding domain (hERLBD) and compare their predicted binding affinity with known antiestrogens. Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were identified as the most promising among all. Of these, Luteolin and Baicalein showed significant anticancer activities against MCF-7 cell line. These findings may provide basic information for the development of anti-breast cancer agents.

scholarly journals BCAS2 Enhances Carcinogenic Effects of Estrogen Receptor Alpha in Breast Cancer Cells

2019 ◽  
Vol 20 (4) ◽  
pp. 966 ◽  
Author(s):  
Ángel Salmerón-Hernández ◽  
María Noriega-Reyes ◽  
Albert Jordan ◽  
Noemi Baranda-Avila ◽  
Elizabeth Langley
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha

Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process modulated by coactivator and corepressor proteins. Breast Cancer Amplified Sequence 2 (BCAS2), is a poorly studied ERα coactivator. In this work, we characterize some of the mechanisms through which this protein increases ERα activity and how this promotes carcinogenic processes in breast cancer cells. Using protein-protein interaction and luciferase assays we show that BCAS2 interacts with ERα both in vitro and in vivo and upregulates transcriptional activation of ERα directly through its N-terminal region (AF-1) and indirectly through its C-terminal (AF-2) region, acting in concert with AF-2 interacting coactivators. Elevated expression of BCAS2 positively affects proliferation, clonogenicity and migration of breast cancer cells and directly activates ERα regulated genes which have been shown to play a role in tumor growth and progression. Finally, we used signal transduction pathway inhibitors to elucidate how BCAS2 is regulated in these cells and observed that BCAS2 is preferentially regulated by the PI3K/AKT signaling pathway. BCAS2 is an AF-1 coactivator of ERα whose overexpression promotes carcinogenic processes, suggesting an important role in the development of estrogen-receptor positive breast cancer.

In Silico Study and In Vitro test of Extract Kaempferia pandurata Roxb. as Anti ER (+) Breast Cancer Cell Line MCF-7

2019 ◽  
Vol 12 (5) ◽  
pp. 2391
Author(s):  
Fadilah Fadilah ◽  
Lowilius Wiyono ◽  
Brenda Cristie Edina ◽  
Risya Amelia Rahmawati ◽  
Linda Erlina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Breast Cancer Cell Line ◽  
In Silico ◽  
Cancer Cell Line ◽  
In Vitro Test ◽  
In Silico Study ◽  
Vitro Test ◽  
Mcf 7
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