title: Methanol extract of Hydroclathrus clathratus suppresses matrix metalloproteinase-9             in T24 bladder carcinoma cells by suppressing the NF-κB and MAPK pathways.
abstract: Hydroclathrus clathratus is a brown marine seaweed and its extract possessing             anti-cancer, anti-herpetic and anti-coagulant activities is a traditional drug             and health food in Korea, Japan and China. However, little is known about the             mechanism by which the methanol extract of H. clathratus (MEHC) inhibits invasion             of cancer cells. In the present study, we investigated the effects of MEHC on             the expression of matrix metalloproteinase-9 (MMP-9) in T24 human bladder carcinoma             cells. Our findings showed that MMP-9 activity was significantly increased in             response to tumor necrosis factor-α (TNF-α). However, treatment with MEHC substantially             reversed TNF-α-induced MMP-9 activity. A matrigel invasion assay also showed that             MEHC reduced TNF-α-induced invasion of T24 bladder carcinoma cells. We also found             that MEHC significantly downregulated the expression of the MMP-9 gene induced             by TNF-α stimulation. Furthermore, we investigated the effects of MEHC on nuclear             factor (NF)-κB activity, which is a potential transcriptional factor for regulating             many invasive genes including MMP-9. MEHC suppressed NF-κB activity by suppressing             IκB degradation and nuclear translocation of the NF-κB p65 and p50 subunits. TNF-α-induced             phosphorylation of phosphatidyl-inositol 3 kinase (PI3K)/Akt and mitogen-activated             protein kinase (MAPK) was significantly downregulated in the presence of MEHC.             Taken together, these results indicate that MEHC is a potential anti-invasive             agent by suppressing TNF-α-induced cancer cell invasion and by specifically inhibiting             NF-κB and MAPKs, as well as downstream target genes such as MMP-9.
authors: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors: R G P T
authors: RG
authors: Jayasooriya
authors: Yung Hyun
authors: YH
authors: Choi
authors: Sung-Kwon
authors: SK
authors: Moon
authors: Wun-Jae
authors: WJ
authors: Kim
authors: Gi-Young
authors: GY
authors: Kim
mesh_terms: D002277:Carcinoma / Q000201:enzymology / Q000378:metabolism*; D002457:Cell Extracts / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D000459:Phaeophyceae / Q000737:chemistry*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D002457:Cell Extracts; D020780:Matrix Metalloproteinase 9; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase