Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway

A. K.M.Moyeenul Huq, Kok Wai Lam, Kamal Rullah, Mohd Fadhlizil Fasihi Mohd Aluwi, Johnson Stanslas, Jamia Azdina Jamal

Research output: Contribution to journalArticle

Abstract

Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson–Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1 μM) and PGR (13.9-fold at 0.01 μM) genes. ERα-mimosine binding energy was −49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.

Original languageEnglish
JournalChemical Biology and Drug Design
DOIs
Publication statusAccepted/In press - 1 Jan 2018

Fingerprint

Mimosine
Cells
Breast Neoplasms
Cell Line
Estradiol
Genes
Cell Proliferation
Molecular mechanics
Hormone Replacement Therapy
MCF-7 Cells
Cell proliferation
Tamoxifen
Molecular Dynamics Simulation
Endometrial Neoplasms
Mechanics
Binding energy
Computer Simulation
Free energy
Molecular dynamics
Cell Survival

Keywords

  • MCF-7 cell line
  • mimosine
  • oestrogenic activity
  • TFF1 and PGR genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway. / Huq, A. K.M.Moyeenul; Lam, Kok Wai; Rullah, Kamal; Mohd Aluwi, Mohd Fadhlizil Fasihi; Stanslas, Johnson; Jamal, Jamia Azdina.

In: Chemical Biology and Drug Design, 01.01.2018.

Research output: Contribution to journalArticle

@article{7b60a96bc7e240bbb4bf38570f9902d9,
title = "Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway",
abstract = "Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson–Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 μM with significant cell proliferation (120.5{\%}) compared to 17β-oestradiol (135.2{\%}). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9{\%}). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9{\%}. It expressed TFF1 (11.1-fold at 0.1 μM) and PGR (13.9-fold at 0.01 μM) genes. ERα-mimosine binding energy was −49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.",
keywords = "MCF-7 cell line, mimosine, oestrogenic activity, TFF1 and PGR genes",
author = "Huq, {A. K.M.Moyeenul} and Lam, {Kok Wai} and Kamal Rullah and {Mohd Aluwi}, {Mohd Fadhlizil Fasihi} and Johnson Stanslas and Jamal, {Jamia Azdina}",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/cbdd.13404",
language = "English",
journal = "Chemical Biology and Drug Design",
issn = "1747-0277",
publisher = "Blackwell",

}

TY - JOUR

T1 - Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway

AU - Huq, A. K.M.Moyeenul

AU - Lam, Kok Wai

AU - Rullah, Kamal

AU - Mohd Aluwi, Mohd Fadhlizil Fasihi

AU - Stanslas, Johnson

AU - Jamal, Jamia Azdina

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson–Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1 μM) and PGR (13.9-fold at 0.01 μM) genes. ERα-mimosine binding energy was −49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.

AB - Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson–Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1 μM) and PGR (13.9-fold at 0.01 μM) genes. ERα-mimosine binding energy was −49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.

KW - MCF-7 cell line

KW - mimosine

KW - oestrogenic activity

KW - TFF1 and PGR genes

UR - http://www.scopus.com/inward/record.url?scp=85055265166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055265166&partnerID=8YFLogxK

U2 - 10.1111/cbdd.13404

DO - 10.1111/cbdd.13404

M3 - Article

C2 - 30251480

AN - SCOPUS:85055265166

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

SN - 1747-0277

ER -