Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF-B and AP-1 activity in human liver cancer cells

被引:84
作者
Hsieh, Ming-Ju [1 ,2 ,3 ]
Lin, Chiao-Wen [4 ,5 ]
Yang, Shun-Fa [3 ,6 ]
Chen, Mu-Kuan [7 ]
Chiou, Hui-Ling [8 ,9 ]
机构
[1] Changhua Christian Hosp, Canc Res Ctr, Changhua, Taiwan
[2] Chung Shan Med Univ, Sch Optometry, Taichung 40201, Taiwan
[3] Chung Shan Med Univ, Inst Med, Taichung 40201, Taiwan
[4] Chung Shan Med Univ, Inst Oral Sci, Taichung 40201, Taiwan
[5] Chung Shan Med Univ Hosp, Dept Dent, Taichung, Taiwan
[6] Chung Shan Med Univ Hosp, Dept Med Res, Taichung, Taiwan
[7] Changhua Christian Hosp, Dept Otorhinolaryngol Head & Neck Surg, Changhua, Taiwan
[8] Chung Shan Med Univ, Sch Med Lab & Biotechnol, Taichung 40201, Taiwan
[9] Chung Shan Med Univ Hosp, Dept Clin Lab, Taichung, Taiwan
关键词
glabridin; migration; invasion; matrix metalloproteinase 9; hepatoma; MATRIX METALLOPROTEINASE-2 AND-9; ORAL-CANCER; TUMOR-METASTASIS; DOWN-REGULATION; KAPPA-B; EXPRESSION; ANGIOGENESIS; GENE; LICORICE; KINASE;
D O I
10.1111/bph.12626
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and Purpose High mortality and morbidity rates for hepatocellular carcinoma in Taiwan primarily result from uncontrolled tumour metastasis. Glabridin, a prenylated isoflavonoid of licorice (Glycyrrhizaglabra) roots, is associated with a wide range of biological properties, such as regulation of energy metabolism, oestrogenic, neuroprotective, anti-osteoporotic and skin whitening. However, the effect of glabridin on the metastasis of tumour cells has not been clarified. Experimental Approach A wound healing model and Boyden chamber assays in vitro were used to determine the effects of glabridin on the migration and invasion of human hepatocellular carcinoma (HHC) cells. Western blot analysis, gelatin zymography, real-time PCR and promoter assays were used to evaluate the inhibitory effects of glabridin on matrix metalloproteinase 9 (MMP9) expression in these cells. Key Results Glabridin significantly inhibited migration/invasion capacities of HCC cells, Huh7 and Sk-Hep-1, cell lines that have low cytotoxicity in vitro, even at high concentrations. Western blot analysis and gelatin zymography showed that glabridin inhibited the expression, activities and protein levels of MMP9 and the phosphorylation of ERK1/2 and JNK1/2. These inhibitory effects were associated with an up-regulation of tissue inhibitor of metalloproteinase-1 and a down-regulation of the transcription factors NF-B and activator protein 1 signalling pathways. Finally, the administration of glabridin effectively suppressed the tumour formation in the hepatoma xenograft model in vivo. Conclusion and Implications Glabridin inhibited the invasion of human HCC cells and may have potential as a chemopreventive agent against liver cancer metastasis.
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收藏
页码:3037 / 3050
页数:14
相关论文
共 36 条
  • [1] Nuclear factor-κ-B:: The enemy within
    Aggarwal, BB
    [J]. CANCER CELL, 2004, 6 (03) : 203 - 208
  • [2] Anti-obesity effects of glabridin-rich supercritical carbon dioxide extract of licorice in high-fat-fed obese mice
    Ahn, Jiyun
    Lee, Hyunjung
    Jang, Jayoung
    Kim, Suna
    Ha, Taeyoul
    [J]. FOOD AND CHEMICAL TOXICOLOGY, 2013, 51 : 439 - 445
  • [3] THE CONCISE GUIDE TO PHARMACOLOGY 2013/14: ENZYMES
    Alexander, Stephen P. H.
    Benson, Helen E.
    Faccenda, Elena
    Pawson, Adam J.
    Sharman, Joanna L.
    Spedding, Michael
    Peters, John A.
    Harmar, Anthony J.
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2013, 170 (08) : 1797 - 1867
  • [4] Structural aspects of the inhibitory effect of glabridin on LDL oxidation
    Belinky, PA
    Aviram, M
    Mahmood, S
    Vaya, J
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1998, 24 (09) : 1419 - 1429
  • [5] The AP-1 site and MMP gene regulation: What is all the fuss about?
    Benbow, U
    Brinckerhoff, CE
    [J]. MATRIX BIOLOGY, 1997, 15 (8-9) : 519 - 526
  • [6] Gelatinase-mediated migration and invasion of cancer cells
    Björklund, M
    Koivunen, E
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2005, 1755 (01): : 37 - 69
  • [7] Antioxidant effect of polyphenolic glabridin on LDL oxidation
    Carmeli, E.
    Fogelman, Y.
    [J]. TOXICOLOGY AND INDUSTRIAL HEALTH, 2009, 25 (4-5) : 321 - 324
  • [8] Role of MMP14 Gene Polymorphisms in Susceptibility and Pathological Development to Hepatocellular Carcinoma
    Chen, Tzy-Yen
    Li, Yi-Ching
    Liu, Yu-Fan
    Tsai, Chiung-Man
    Hsieh, Yi-Hsien
    Lin, Chiao-Wen
    Yang, Shun-Fa
    Weng, Chia-Jui
    [J]. ANNALS OF SURGICAL ONCOLOGY, 2011, 18 (08) : 2348 - 2356
  • [9] Dioscorea nipponica Makino inhibits migration and invasion of human oral cancer HSC-3 cells by transcriptional inhibition of matrix metalloproteinase-2 through modulation of CREB and AP-1 activity
    Chien, Ming-Hsien
    Ying, Tsung-Ho
    Hsieh, Yih-Shou
    Chang, Yu-Chao
    Yeh, Chia-Ming
    Ko, Jiunn-Liang
    Lee, Wen-Sen
    Chang, Jer-Hua
    Yang, Shun-Fa
    [J]. FOOD AND CHEMICAL TOXICOLOGY, 2012, 50 (3-4) : 558 - 566
  • [10] Matrix metalloproteinases and the development of cancer
    Coussens, LM
    Werb, Z
    [J]. CHEMISTRY & BIOLOGY, 1996, 3 (11): : 895 - 904