ReferenceID 6144

In vitro anti-motile effects of Rhoifolin, a flavonoid extracted from Callicarpa nudiflora on breast cancer cells via downregulating Podocalyxin-Ezrin interaction during Epithelial Mesenchymal Transition

Phytomedicine

BACKGROUND: Callicarpa nudiflora (C. nudiflora), which is a medical herb in genus of Callicarpa, widely grows in the southern part of China. Several investigations had shown that this herb exerts anti-tumor effects. Ezri

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Reference Id
6144
Evidence Id
22734
Core Evidence Id
22734
Source Reference Id
5551
Herb2 Reference Id
HBREF006348
Subject Paper Key
HBIN042285_34649211
Pubmed Id
34649211
Doi
10.1016/j.phymed.2021.153486
Paper Title
In vitro anti-motile effects of Rhoifolin, a flavonoid extracted from Callicarpa nudiflora on breast cancer cells via downregulating Podocalyxin-Ezrin interaction during Epithelial Mesenchymal Transition
Paper Abstract
BACKGROUND: Callicarpa nudiflora (C. nudiflora), which is a medical herb in genus of Callicarpa, widely grows in the southern part of China. Several investigations had shown that this herb exerts anti-tumor effects. Ezrin is an important membrane-cytoskeleton-binding protein. By organizing membrane proteins and orchestrating their signal transduction, Ezrin contributes to modulation of cytoskeleton rearrangement in cell motility. PURPOSE: To investigate the anti-motile properties of Rhoifolin (RFL), a flavonoid from C. nudiflora, and to determine whether its effects are related to the inhibition on Podocalyxin (PODXL)-Ezrin signal transduction. METHODS: To determine suitable concentration of RFL and exposure time on breast cancer cells, the effects of RFL on viability of breast cancer cells were evaluated by MTT assay. Then, the anti-migratory properties of RFL were determined by AP 48 chamber system and ORISTM cell migration assay. F-actin in MDA-MB-231 cells was visualized by Alexa Fluor 488 conjugated Phalloidin. Immunoprecipitation was involved to access the effects of RFL on the interaction between Ezrin and PODXL. In addition, several EMT markers, including E-cadherin, Vimentin, Snail and Slug, were measured by Western Blotting assay and cell immunofluorescent analysis. Finally, the effects of RFL on cell migration, expression of Ezrin and EMT markers were verified by small interfering RNA (siRNA) mediated gene silencing. RESULTS: We showed here that treatments with 10 and 40 muM of RFL induced significant inhibitions on cell migration and alterations on the location and organization of actin cytoskeleton in breast cancer cells. Next, it was found that RFL suppressed Ezrin phosphorylation and consequent interaction with PODXL, significantly. Also, this compound showed an obvious inhibitory effect on TGF-beta1-induced EMT in MDA-MB-231 cells. Furthermore, data from RNA interfering assay confirmed that the inhibitory effects of RFL on Ezrin was enhanced by the deletion of Ezrin. CONCLUSION: RFL shows anti-motile properties on breast cancer cells, which is due to its potential to downregulate Podocalyxin-Ezrin interaction during Epithelial Mesenchymal Transition.
Journal
Phytomedicine
Publish Year
2021
Experiment Subject
mda-mb-231 cells
Experiment Type
Cell Experiment
Phenotype Related
Breast Cancer
Paper Title Cn
Paper Title En
In vitro anti-motile effects of Rhoifolin, a flavonoid extracted from Callicarpa nudiflora on breast cancer cells via downregulating Podocalyxin-Ezrin interaction during Epithelial Mesenchymal Transition
Bilingual Status
semi_complete