Abstract
Myricetin is a commonly found dietary flavonoid. In the present study, we investigated the effects of myricetin on migration and invasion of radioresistant lung cancer cells (A549‐IR). Transcriptome analysis of A549‐IR cells identified several differentially expressed genes (DEGs) in A549‐IR cells compared to parental A549 cells. Functional enrichment analysis revealed that most of the DEGs were linked with PI3K‐AKT signaling, proteoglycans, focal adhesion, and ECM–receptor interactions. A549‐IR cells demonstrated enhanced migratory potential with increased expression of vimentin, snail and slug, and reduced expression of E‐cadherin. A549‐IR cells exposed to myricetin displayed reduced migration and suppressed MMP‐2 and MMP‐9 expression. Notably, myricetin inhibited the phosphorylation of focal adhesion kinase (FAK) and altered the F‐actin/G‐actin ratio in A549‐IR cells, without modulation of EMT markers. These findings suggest that myricetin can inhibit migration of A549‐IR cells by suppressing MMP‐2 and MMP‐9 expressions through inhibition of the FAK‐ERK signaling pathway.
Highlights
Lung cancer remains as a major health issue among men and women worldwide
Given the influence of radiotherapy in the enhancement of metastatic ability in cancer patients, establishment of new in vitro models to investigate preclinical efficacy of novel drug leads on reversing radiation-induced metastasis will underpin cancer therapeutics
Results of the gelatin zymography analysis confirmed that myricetin can reduce the expression of matrix metalloproteinases (MMPs)-2 (Figure 4e). These results indicate that myricetin can barely induce mesenchymal–epithelial transition (MET) in A549-IR cells, while suppressing migration of A549-IR cells through reducing MMP-2 and MMP-9 expression levels
Summary
Lung cancer remains as a major health issue among men and women worldwide. In the United Sates, lung cancer is the second major cause of cancer death in men (Siegel, Miller, & Jemal, 2019). Given the influence of radiotherapy in the enhancement of metastatic ability in cancer patients, establishment of new in vitro models to investigate preclinical efficacy of novel drug leads on reversing radiation-induced metastasis will underpin cancer therapeutics. In this investigation, radiationinduced metastatic cancer cell line (A549-IR) was established from parental A549 lung cancer cells, and metastasis inhibitory effects of myricetin in A549-IR cells were examined to provide alternative cancer therapeutic approaches to improve the life expectancy of NSCLC patients
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