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L-carnosine inhibits metastasis of SK-Hep-1 cells by inhibition of matrix metaoproteinase-9 expression and induction of an antimetastatic gene, nm23-H1.

Abstract

Antioxidants have been suggested to inhibit the expression of matrix metalloproteinases (MMPs), especially MMP-9, which plays a critical role in tumor metastasis. Because of its antioxidant activity and the ability to chelate divalent cations, L-carnosine (LC) was tested for inhibition of MMP-9 in a highly invasive hepatocarcinoma, SK-Hep-1 cells. We found that LC (50-1,000 microM) did not directly inhibit the activity of MMP-9 in a cell-free system. However, LC significantly inhibited the expression and activity of MMP-9 protein in SK-Hep-1 cells [inhibitory concentration of 50% (IC(50))| = 105 and 63 muM, respectively). Whereas LC did not inhibit the viability of SK-Hep-1 cells at concentrations up to 1,000 microM within 3 days of incubation, this dipeptide significantly inhibited cell migration (IC(50) = 82 microM) and invasion (IC(50) = 113 microM). LC significantly (P < 0.05) and dose dependently enhanced the expression of an antimetastatic gene, nonmetastatic cells 1, protein (nm23)-H1, at both protein and messenger ribonucleic acid (mRNA) levels. MMP-9 activity inversely correlated significantly with the expression of protein (r(2) = 0.77, P < 0.001) and mRNA (r(2) = 0.65, P < 0.001) of nm23-H1 in LC-treated cells. Thus, LC can inhibit the migration and invasion of SK-Hep-1 cells, and the effect is likely associated with upregulation of nm23-H1 and downregulation of MMP-9 expression.

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  • Authors+Show Affiliations

    ,

    Department of Food and Nutrition, Hungkuang University, Taichung County, Taiwan, Republic of China.

    Source

    Nutrition and cancer 60:4 2008 pg 526-33

    MeSH

    Carcinoma, Hepatocellular
    Carnosine
    Cell Line, Tumor
    Cell Movement
    Enzyme Inhibitors
    Gene Expression
    Humans
    Liver Neoplasms
    Matrix Metalloproteinase 9
    Matrix Metalloproteinase Inhibitors
    NM23 Nucleoside Diphosphate Kinases
    Neoplasm Invasiveness
    Neoplasm Metastasis
    RNA, Messenger

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18584487

    Citation

    Chuang, Cheng-Hung, and Miao-Lin Hu. "L-carnosine Inhibits Metastasis of SK-Hep-1 Cells By Inhibition of Matrix Metaoproteinase-9 Expression and Induction of an Antimetastatic Gene, Nm23-H1." Nutrition and Cancer, vol. 60, no. 4, 2008, pp. 526-33.
    Chuang CH, Hu ML. L-carnosine inhibits metastasis of SK-Hep-1 cells by inhibition of matrix metaoproteinase-9 expression and induction of an antimetastatic gene, nm23-H1. Nutr Cancer. 2008;60(4):526-33.
    Chuang, C. H., & Hu, M. L. (2008). L-carnosine inhibits metastasis of SK-Hep-1 cells by inhibition of matrix metaoproteinase-9 expression and induction of an antimetastatic gene, nm23-H1. Nutrition and Cancer, 60(4), pp. 526-33. doi:10.1080/01635580801911787.
    Chuang CH, Hu ML. L-carnosine Inhibits Metastasis of SK-Hep-1 Cells By Inhibition of Matrix Metaoproteinase-9 Expression and Induction of an Antimetastatic Gene, Nm23-H1. Nutr Cancer. 2008;60(4):526-33. PubMed PMID: 18584487.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - L-carnosine inhibits metastasis of SK-Hep-1 cells by inhibition of matrix metaoproteinase-9 expression and induction of an antimetastatic gene, nm23-H1. AU - Chuang,Cheng-Hung, AU - Hu,Miao-Lin, PY - 2008/6/28/pubmed PY - 2008/11/11/medline PY - 2008/6/28/entrez SP - 526 EP - 33 JF - Nutrition and cancer JO - Nutr Cancer VL - 60 IS - 4 N2 - Antioxidants have been suggested to inhibit the expression of matrix metalloproteinases (MMPs), especially MMP-9, which plays a critical role in tumor metastasis. Because of its antioxidant activity and the ability to chelate divalent cations, L-carnosine (LC) was tested for inhibition of MMP-9 in a highly invasive hepatocarcinoma, SK-Hep-1 cells. We found that LC (50-1,000 microM) did not directly inhibit the activity of MMP-9 in a cell-free system. However, LC significantly inhibited the expression and activity of MMP-9 protein in SK-Hep-1 cells [inhibitory concentration of 50% (IC(50))| = 105 and 63 muM, respectively). Whereas LC did not inhibit the viability of SK-Hep-1 cells at concentrations up to 1,000 microM within 3 days of incubation, this dipeptide significantly inhibited cell migration (IC(50) = 82 microM) and invasion (IC(50) = 113 microM). LC significantly (P < 0.05) and dose dependently enhanced the expression of an antimetastatic gene, nonmetastatic cells 1, protein (nm23)-H1, at both protein and messenger ribonucleic acid (mRNA) levels. MMP-9 activity inversely correlated significantly with the expression of protein (r(2) = 0.77, P < 0.001) and mRNA (r(2) = 0.65, P < 0.001) of nm23-H1 in LC-treated cells. Thus, LC can inhibit the migration and invasion of SK-Hep-1 cells, and the effect is likely associated with upregulation of nm23-H1 and downregulation of MMP-9 expression. SN - 1532-7914 UR - https://www.unboundmedicine.com/medline/citation/18584487/L_carnosine_inhibits_metastasis_of_SK_Hep_1_cells_by_inhibition_of_matrix_metaoproteinase_9_expression_and_induction_of_an_antimetastatic_gene_nm23_H1_ L2 - http://www.tandfonline.com/doi/full/10.1080/01635580801911787 DB - PRIME DP - Unbound Medicine ER -