Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1

G protein-coupled estrogen receptor 1 (GPER1) is a potential therapeutic target for treating triple-negative breast cancers (TNBC). However, modulators for GPER1 that can be used to treat TNBC have not appeared. Berberine (BBR) is a bioactive isoquinoline alkaloid with high oral safety. In recent ye...

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Autores principales:	Miaomiao Qi, Xiang Liu, Ying Zhou, Haoyu Wang, Ying Zhao, Jing Ren, Jin Xiang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	berberine binding co-localization GPER1 MAP1LC3 NF-κB Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/07058c31455d4bdaa6655fe7ee9f56ec
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spelling	oai:doaj.org-article:07058c31455d4bdaa6655fe7ee9f56ec2021-11-11T16:55:44ZBerberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 110.3390/ijms2221114661422-00671661-6596https://doaj.org/article/07058c31455d4bdaa6655fe7ee9f56ec2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11466https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067G protein-coupled estrogen receptor 1 (GPER1) is a potential therapeutic target for treating triple-negative breast cancers (TNBC). However, modulators for GPER1 that can be used to treat TNBC have not appeared. Berberine (BBR) is a bioactive isoquinoline alkaloid with high oral safety. In recent years, BBR has shown an inhibitory effect on TNBC tumors such as MDA-MB-231, but the molecular target remains unclear, which hinders related clinical research. Our work proved that BBR is a modulator of GPER1 that can inhibit cell viability, migration, and autophagy of MDA-MB-231 cells. The inhibitory effect of BBR on MDA-MB-231 cells has a dependence on estrogen levels. Although BBR promoted the proteasome, which is a major factor in the degradation of GPER1, it could still induce the protein level of GPER1. Correspondingly, the transcription of cellular communication network factor 2 (CCN2) was promoted. BBR could bind to GPER1 directly and change the secondary structure of GPER1, as in the case of 17β-estradiol (E2). In addition, BBR induced not only a high degree of co-localization of GPER1 and microtubule-associated protein 1 light chain 3 (MAP1LC3), but also the accumulation of sequestosome 1 (SQSTM1/p62) by the inhibition of the nuclear translocation of the nuclear factor-kappa B (NF-κB) subunit (RELA/p65), which indicates NF-κB inhibition and anti-cancer effects. This result proved that the promotional effect of BBR on the GPER1/NF-κB pathway was closely related to its inhibitory effect on autophagy, which may serve as a new mechanism by which to explain the inhibitory effect of BBR on MDA-MB-231 cells and expand our understanding of the function of both BBR and GPER1.Miaomiao QiXiang LiuYing ZhouHaoyu WangYing ZhaoJing RenJin XiangMDPI AGarticleberberinebindingco-localizationGPER1MAP1LC3NF-κBBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11466, p 11466 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	berberine binding co-localization GPER1 MAP1LC3 NF-κB Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	berberine binding co-localization GPER1 MAP1LC3 NF-κB Biology (General) QH301-705.5 Chemistry QD1-999 Miaomiao Qi Xiang Liu Ying Zhou Haoyu Wang Ying Zhao Jing Ren Jin Xiang Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
description	G protein-coupled estrogen receptor 1 (GPER1) is a potential therapeutic target for treating triple-negative breast cancers (TNBC). However, modulators for GPER1 that can be used to treat TNBC have not appeared. Berberine (BBR) is a bioactive isoquinoline alkaloid with high oral safety. In recent years, BBR has shown an inhibitory effect on TNBC tumors such as MDA-MB-231, but the molecular target remains unclear, which hinders related clinical research. Our work proved that BBR is a modulator of GPER1 that can inhibit cell viability, migration, and autophagy of MDA-MB-231 cells. The inhibitory effect of BBR on MDA-MB-231 cells has a dependence on estrogen levels. Although BBR promoted the proteasome, which is a major factor in the degradation of GPER1, it could still induce the protein level of GPER1. Correspondingly, the transcription of cellular communication network factor 2 (CCN2) was promoted. BBR could bind to GPER1 directly and change the secondary structure of GPER1, as in the case of 17β-estradiol (E2). In addition, BBR induced not only a high degree of co-localization of GPER1 and microtubule-associated protein 1 light chain 3 (MAP1LC3), but also the accumulation of sequestosome 1 (SQSTM1/p62) by the inhibition of the nuclear translocation of the nuclear factor-kappa B (NF-κB) subunit (RELA/p65), which indicates NF-κB inhibition and anti-cancer effects. This result proved that the promotional effect of BBR on the GPER1/NF-κB pathway was closely related to its inhibitory effect on autophagy, which may serve as a new mechanism by which to explain the inhibitory effect of BBR on MDA-MB-231 cells and expand our understanding of the function of both BBR and GPER1.
format	article
author	Miaomiao Qi Xiang Liu Ying Zhou Haoyu Wang Ying Zhao Jing Ren Jin Xiang
author_facet	Miaomiao Qi Xiang Liu Ying Zhou Haoyu Wang Ying Zhao Jing Ren Jin Xiang
author_sort	Miaomiao Qi
title	Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
title_short	Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
title_full	Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
title_fullStr	Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
title_full_unstemmed	Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
title_sort	berberine inhibits mda-mb-231 cells as an agonist of g protein-coupled estrogen receptor 1
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/07058c31455d4bdaa6655fe7ee9f56ec
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_version_	1718432159840075776

Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1

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