Baicalein inhibits non‐small‐cell lung cancer invasion and metastasis by reducing ezrin tension in inflammation microenvironment
Open Access
- 21 July 2020
- journal article
- research article
- Published by Wiley in Cancer Science
- Vol. 111 (10), 3802-3812
- https://doi.org/10.1111/cas.14577
Abstract
Baicalein, a flavonoid phytochemical, has been proved to be effective in anti‐metastatic activity for various cancers, especially for non‐small cell lung cancer (NSCLC). However, the underlying mechanism of how Baicalein targets the cellular mechanical activities during NSCLC cell invasion and metastasis remains elusive. In this study, we found that non‐cytotoxic concentration of Baicalein still retain anti‐dissemination activity both in vitro and in vivo . Using the genetic encoding tension probe based on Förster resonance energy transfer (FRET) theory, Baicalein significantly decreases ezrin tension by down‐regulating the cellular ezrin‐SNO levels in NSCLC cells in the inflammatory microenvironment. Moreover, the decreased ezrin tension inhibits the formation of aggressive phenotype of NSCLC cells and leader cells in collective migration, and subsequently suppresses NSCLC dissemination. Baicalein restrains SNO‐mediated ezrin tension via decreasing the expression level of iNOS. Overall this study demonstrates the novel mechanism of Baicalein in suppressing NSCLC invasion and metastasis from the perspective of mechanopharmacology and shows a new direction for drug development.Keywords
Funding Information
- National Natural Science Foundation of China (81573409)
This publication has 42 references indexed in Scilit:
- Baicalein Inhibits the Invasion and Metastatic Capabilities of Hepatocellular Carcinoma Cells via Down-Regulation of the ERK PathwayPLOS ONE, 2013
- Protein S-nitrosylation and cancerCancer Letters, 2012
- RETRACTED ARTICLE: Baicalein mediates inhibition of migration and invasiveness of skin carcinoma through Ezrin in A431 cellsBMC Cancer, 2011
- Mechanical compression drives cancer cells toward invasive phenotypeProceedings of the National Academy of Sciences, 2011
- The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and functionNature Reviews Molecular Cell Biology, 2011
- Collective cell guidance by cooperative intercellular forcesNature Materials, 2011
- Organizing the cell cortex: the role of ERM proteinsNature Reviews Molecular Cell Biology, 2010
- Mechanics, malignancy, and metastasis: The force journey of a tumor cellCancer and Metastasis Reviews, 2009
- Expression, Localization, and Binding Activity of the Ezrin/Radixin/Moesin Proteins in the Mouse TestisJournal of Histochemistry & Cytochemistry, 2008
- Collective migration of an epithelial monolayer in response to a model woundProceedings of the National Academy of Sciences, 2007