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
- 306 Downloads
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
- 12.Petrella BL, Armstrong DA, Vincenti MP. CCAA T-enhancer-binding protein beta activation of MMP-1 gene expression in SW1353 cells: independent roles of extracellular signal-regulated and p90/ribosomal S6 kinases. J Cell Physiol. 2011;226:3349–54.Google Scholar
- 15.Husmann K, Arlt MJ, Muff R, Langsam B, Bertz J, et al. Matrix metalloproteinase 1 promotes tumor formation and lung metastasis in an intratibial injection osteosarcoma mouse model. Biochim Biophys Acta. 1832;2013:347–54.Google Scholar
- 22.Tsai JP, Hsiao PC, Yang SF, Hsieh SC, Bau DT, et al. Licochalcone A suppresses migration and invasion of human hepatocellular carcinoma cells through downregulation of MKK4/JNK via NF-kappaB mediated urokinase plasminogen activator expression. PLoS One. 2014;9:e86537.PubMedCentralPubMedCrossRefGoogle Scholar
- 23.Green JA, Elkington PT, Pennington CJ, Roncaroli F, Dholakia S, et al. Mycobacterium tuberculosis upregulates microglial matrix metalloproteinase-1 and -3 expression and secretion via NF-kappaB- and activator protein-1-dependent monocyte networks. J Immunol. 2010;184:6492–503.PubMedCrossRefGoogle Scholar
- 37.Shen H, Zeng G, Tang G, Cai X. Bi L, et al. Tumour Biol: Antimetastatic effects of licochalcone A on oral cancer via regulating metastasis-associated proteases; 2014.Google Scholar
- 44.Sze KM, Wong KL, Chu GK, Lee JM, Yau TO, et al. Loss of phosphatase and tensin homolog enhances cell invasion and migration through AKT/Sp-1 transcription factor/matrix metalloproteinase 2 activation in hepatocellular carcinoma and has clinicopathologic significance. Hepatology. 2011;53:1558–69.PubMedCrossRefGoogle Scholar
- 47.Roy Choudhury S, Karmakar S, Banik NL, Ray SK. Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification. Invest New Drugs. 2010;28:812–24.PubMedCrossRefGoogle Scholar