Licochalcone A inhibits the migration and invasion of human lung cancer cells via inactivation of the Akt signaling pathway with downregulation of MMP-1/-3 expression

Abstract

Licochalcone A (LicA), a major phenolic constituent of Glycyrrhiza inflata, has been reported to exhibit anti-tumor, anti-inflammatory, and anti-metastatic properties in various cancer cells and animal models. The aim of this study was to determine the anti-tumor effects of LicA on lung cancer cells. The results indicated that LicA exhibited effective inhibition of cell migration and invasion of A549 and H460 cells under non-cytotoxic concentrations. Furthermore, LicA was also found to significantly inhibit the proteins and messenger RNA (mRNA) expression of MMP-1 and MMP-3 in A549 cells. Moreover, treatment of A549 cells with LicA-inhibited activation of the phosphorylation of Akt and inhibition of Akt by LY294002 (PI3K inhibitor) or transfection with the constitutive active-Akt (CA-Akt) expression vector significantly abolished the LicA-inhibited migration and invasion through activation of the Akt pathway. Further mechanistic studies revealed that LicA inhibits Akt signaling pathways and downstream transcription factors Sp1 expression. These findings imply a critical role for Akt inhibition in the LicA-inhibited migration and invasion of lung cancer cells. Thus, LicA might be used as an anti-invasive agent in the treatment of lung cancer.

Naringenin inhibits migration of lung cancer cells via the inhibition of matrix metalloproteinases-2 and −9

“…Extracts from Ecklonia cava that were enriched in polyphenol suppress the migration of lung A549 cells via the downregulation of AKT and MMP-2 activities (25). In addition, licochalcone A attenuated the migration of lung A549 cells by the downregulation of the AKT activity and suppression of the MMP-1 and -3 expression (24). In the present study, treatment with naringenin reduced the phosphorylation of AKT in a dose-dependent manner.…”

“…However, it blocked the activities of AKT by wortmannin and also suppressed MMP-2 expression (23). Previous reports have demonstrated that polyphenol isolated from vegetables and fruits inhibited lung cancer migration through the reduction of the AKT activity (24,25). Extracts from Ecklonia cava that were enriched in polyphenol suppress the migration of lung A549 cells via the downregulation of AKT and MMP-2 activities (25).…”

Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells

“…The data from the present study demonstrated that Licochalcone A decreases cell viability, induces apoptosis and increases the caspase-3 activity in MCF-7 cells. Previous studies have demonstrated that Licochalcone A suppresses growth of human esophageal carcinoma (14), human lung cancer (15) and human oral cancer cells (16).…”

Chemopreventive Effects of Licorice and Its Components

“…Additionally, LicA suppressed the expression of NF-κB and its binding to the uPA promoter [109]. Others reported that LicA effectively inhibited migration and invasion of A549 and H460 lung cancer cells [110]. The compound also significantly inhibited the protein and gene expression of MMP-1 and MMP-3 in A549 cells.…”

“…The compound also significantly inhibited the protein and gene expression of MMP-1 and MMP-3 in A549 cells. Treatment of A549 cells with LicA suppressed phosphorylation of Akt, an effect, along with inhibition of migration and invasion, that was reversed by treatment with LY294002 (PI3-K inhibitor) or transfection with constitutive active-Akt i [110].…”