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

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...

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Main Authors:	Huq, AKM Moyeenul, Wai, Lam Kok, Rullah, Kamal, Mohd Aluwi, Mohd Fadhlizil Fasihi, Stanslas, Johnson, Jamal, Jamia Azdina
Format:	Article
Language:	English English
Published:	Wiley Online Library 2019
Subjects:	RM Therapeutics. Pharmacology RS403 Materia Medica-Pharmaceutical Chemistry
Online Access:	http://irep.iium.edu.my/74950/ http://irep.iium.edu.my/74950/ http://irep.iium.edu.my/74950/ http://irep.iium.edu.my/74950/1/Kamal%20Rullah%2018.pdf http://irep.iium.edu.my/74950/3/2019-Chemical_Biology_%26_Drug_Design.pdf

id	iium-74950
recordtype	eprints
spelling	iium-749502019-11-07T08:20:49Z http://irep.iium.edu.my/74950/ Oestrogenic activity of mimosine on MCF‐7 breast cancer cell line through the ERα‐mediated pathway Huq, AKM Moyeenul Wai, Lam Kok Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Stanslas, Johnson Jamal, Jamia Azdina RM Therapeutics. Pharmacology RS403 Materia Medica-Pharmaceutical Chemistry 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. Wiley Online Library 2019-03 Article PeerReviewed application/pdf en http://irep.iium.edu.my/74950/1/Kamal%20Rullah%2018.pdf application/pdf en http://irep.iium.edu.my/74950/3/2019-Chemical_Biology_%26_Drug_Design.pdf Huq, AKM Moyeenul and Wai, Lam Kok and Rullah, Kamal and Mohd Aluwi, Mohd Fadhlizil Fasihi and Stanslas, Johnson and Jamal, Jamia Azdina (2019) Oestrogenic activity of mimosine on MCF‐7 breast cancer cell line through the ERα‐mediated pathway. Chemical Biology and Drug Design, 93 (3). pp. 1-10. ISSN 1747-0285 (In Press) https://onlinelibrary.wiley.com/doi/abs/10.1111/cbdd.13404 10.1111/cbdd.13404
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	RM Therapeutics. Pharmacology RS403 Materia Medica-Pharmaceutical Chemistry
spellingShingle	RM Therapeutics. Pharmacology RS403 Materia Medica-Pharmaceutical Chemistry Huq, AKM Moyeenul Wai, Lam Kok Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Stanslas, Johnson Jamal, Jamia Azdina Oestrogenic activity of mimosine on MCF‐7 breast cancer cell line through the ERα‐mediated pathway
description	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.
format	Article
author	Huq, AKM Moyeenul Wai, Lam Kok Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Stanslas, Johnson Jamal, Jamia Azdina
author_facet	Huq, AKM Moyeenul Wai, Lam Kok Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Stanslas, Johnson Jamal, Jamia Azdina
author_sort	Huq, AKM Moyeenul
title	Oestrogenic activity of mimosine on MCF‐7 breast cancer cell line through the ERα‐mediated pathway
title_short	Oestrogenic activity of mimosine on MCF‐7 breast cancer cell line through the ERα‐mediated pathway
title_full	Oestrogenic activity of mimosine on MCF‐7 breast cancer cell line through the ERα‐mediated pathway
title_fullStr	Oestrogenic activity of mimosine on MCF‐7 breast cancer cell line through the ERα‐mediated pathway
title_full_unstemmed	Oestrogenic activity of mimosine on MCF‐7 breast cancer cell line through the ERα‐mediated pathway
title_sort	oestrogenic activity of mimosine on mcf‐7 breast cancer cell line through the erα‐mediated pathway
publisher	Wiley Online Library
publishDate	2019
url	http://irep.iium.edu.my/74950/ http://irep.iium.edu.my/74950/ http://irep.iium.edu.my/74950/ http://irep.iium.edu.my/74950/1/Kamal%20Rullah%2018.pdf http://irep.iium.edu.my/74950/3/2019-Chemical_Biology_%26_Drug_Design.pdf
first_indexed	2023-09-18T21:46:04Z
last_indexed	2023-09-18T21:46:04Z
_version_	1777413458056183808

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

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