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
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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.
KeywordsLung cancer cells LicA Migration Invasion MMP-1 MMP-3 Sp1
This work was supported by grants from Chung Shan Medical University and Changhua Christian Hospital, Changhua, Taiwan (CSMU-CCH-102-05) and National Science Council, Taiwan (NSC 101-2313-B-040-001).
Conflicts of interest
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