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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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Tumor Biology

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. Visiting staff, Division of General thoracic Surgery, Department of surgery, Changhua Christian Hospital, Changhua, Taiwan

    Hung-Che Huang

  2. School of Dentistry, Chung Shan Medical University, Taichung, Taiwan

    Lo-Lin Tsai

  3. Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan

    Lo-Lin Tsai

  4. Department of Nephrology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

    Jen-Pi Tsai

  5. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Shu-Ching Hsieh & Shun-Fa Yang

  6. Institute of Biochemistry and Biotechnology, Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Jung-Tsung Hsueh & Yi-Hsien Hsieh

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  1. Hung-Che Huang
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Correspondence to Yi-Hsien Hsieh.

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Huang, HC., Tsai, LL., Tsai, JP. et al. 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. Tumor Biol. 35, 12139–12149 (2014). https://doi.org/10.1007/s13277-014-2519-3

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