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Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment

Baicalein, a flavonoid phytochemical, has been shown to be effective as an anti‐metastatic agent for various cancers, especially for non‐small‐cell lung cancer (NSCLC). However, the underlying mechanism of how baicalein targets cellular processes during NSCLC cell invasion and metastasis remains elu...

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Autores principales: Zhang, Xiaolong, Ruan, Qinli, Zhai, Yiqian, Lu, Dandan, Li, Chen, Fu, Yahan, Zheng, Zihui, Song, Ying, Guo, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540981/
https://www.ncbi.nlm.nih.gov/pubmed/32691974
http://dx.doi.org/10.1111/cas.14577
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author Zhang, Xiaolong
Ruan, Qinli
Zhai, Yiqian
Lu, Dandan
Li, Chen
Fu, Yahan
Zheng, Zihui
Song, Ying
Guo, Jun
author_facet Zhang, Xiaolong
Ruan, Qinli
Zhai, Yiqian
Lu, Dandan
Li, Chen
Fu, Yahan
Zheng, Zihui
Song, Ying
Guo, Jun
author_sort Zhang, Xiaolong
collection PubMed
description Baicalein, a flavonoid phytochemical, has been shown to be effective as an anti‐metastatic agent for various cancers, especially for non‐small‐cell lung cancer (NSCLC). However, the underlying mechanism of how baicalein targets cellular processes during NSCLC cell invasion and metastasis remains elusive. In this study, we found that non‐cytotoxic concentrations of baicalein still retained anti‐dissemination activity both in vitro and in vivo. Using a genetic encoding tension probe based on Förster resonance energy transfer (FRET) theory, baicalein was shown to significantly decrease ezrin tension by downregulating cellular ezrin S‐nitrosylation (SNO) levels in NSCLC cells in the inflammatory microenvironment. Decreased ezrin tension inhibited the formation of an aggressive phenotype of NSCLC cell and leader cell in collective migration, and subsequently suppressed NSCLC dissemination. Baicalein restrained SNO‐mediated ezrin tension by decreasing iNOS expression levels. Overall this study demonstrates the novel mechanism used by baicalein to suppress NSCLC invasion and metastasis from a mechanopharmacology perspective and illustrates a new direction for drug development.
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spelling pubmed-75409812020-10-09 Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment Zhang, Xiaolong Ruan, Qinli Zhai, Yiqian Lu, Dandan Li, Chen Fu, Yahan Zheng, Zihui Song, Ying Guo, Jun Cancer Sci Drug Discovery and Delivery Baicalein, a flavonoid phytochemical, has been shown to be effective as an anti‐metastatic agent for various cancers, especially for non‐small‐cell lung cancer (NSCLC). However, the underlying mechanism of how baicalein targets cellular processes during NSCLC cell invasion and metastasis remains elusive. In this study, we found that non‐cytotoxic concentrations of baicalein still retained anti‐dissemination activity both in vitro and in vivo. Using a genetic encoding tension probe based on Förster resonance energy transfer (FRET) theory, baicalein was shown to significantly decrease ezrin tension by downregulating cellular ezrin S‐nitrosylation (SNO) levels in NSCLC cells in the inflammatory microenvironment. Decreased ezrin tension inhibited the formation of an aggressive phenotype of NSCLC cell and leader cell in collective migration, and subsequently suppressed NSCLC dissemination. Baicalein restrained SNO‐mediated ezrin tension by decreasing iNOS expression levels. Overall this study demonstrates the novel mechanism used by baicalein to suppress NSCLC invasion and metastasis from a mechanopharmacology perspective and illustrates a new direction for drug development. John Wiley and Sons Inc. 2020-08-27 2020-10 /pmc/articles/PMC7540981/ /pubmed/32691974 http://dx.doi.org/10.1111/cas.14577 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Drug Discovery and Delivery
Zhang, Xiaolong
Ruan, Qinli
Zhai, Yiqian
Lu, Dandan
Li, Chen
Fu, Yahan
Zheng, Zihui
Song, Ying
Guo, Jun
Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment
title Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment
title_full Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment
title_fullStr Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment
title_full_unstemmed Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment
title_short Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment
title_sort baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment
topic Drug Discovery and Delivery
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540981/
https://www.ncbi.nlm.nih.gov/pubmed/32691974
http://dx.doi.org/10.1111/cas.14577
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