ReferenceID 4717
Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
Int J Mol Sci
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. Berberin
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4717
- Evidence Id
- 21307
- Core Evidence Id
- 21307
- Source Reference Id
- 2684
- Herb2 Reference Id
- HBREF003481
- Subject Paper Key
- HBIN017893_34768896
- Pubmed Id
- 34768896
- Doi
- 10.3390/ijms222111466
- Paper Title
- Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
- Paper Abstract
- 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 17beta-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-kappaB) subunit (RELA/p65), which indicates NF-kappaB inhibition and anti-cancer effects. This result proved that the promotional effect of BBR on the GPER1/NF-kappaB 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.
- Journal
- Int J Mol Sci
- Publish Year
- 2021
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Tnbc Tumors; Triple-negative Breast Cancers
- Paper Title Cn
- Paper Title En
- Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1
- Bilingual Status
- semi_complete