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Hydroclathrus clathratus is a brown marine seaweed and its extract possessinganti-cancer, anti-herpetic and anti-coagulant activities is a traditional drugand health food in Korea, Japan and China. However, little is known about themechanism by which the methanol extract of H. clathratus (MEHC) inhibits invasionof cancer cells. In the present study, we investigated the effects of MEHC onthe expression of matrix metalloproteinase-9 (MMP-9) in T24 human bladder carcinomacells. Our findings showed that MMP-9 activity was significantly increased inresponse to tumor necrosis factor-α (TNF-α). However, treatment with MEHC substantiallyreversed TNF-α-induced MMP-9 activity. A matrigel invasion assay also showed thatMEHC reduced TNF-α-induced invasion of T24 bladder carcinoma cells. We also foundthat MEHC significantly downregulated the expression of the MMP-9 gene inducedby TNF-α stimulation. Furthermore, we investigated the effects of MEHC on nuclearfactor (NF)-κB activity, which is a potential transcriptional factor for regulatingmany invasive genes including MMP-9. MEHC suppressed NF-κB activity by suppressingIκB degradation and nuclear translocation of the NF-κB p65 and p50 subunits. TNF-α-inducedphosphorylation of phosphatidyl-inositol 3 kinase (PI3K)/Akt and mitogen-activatedprotein kinase (MAPK) was significantly downregulated in the presence of MEHC.Taken together, these results indicate that MEHC is a potential anti-invasiveagent by suppressing TNF-α-induced cancer cell invasion and by specifically inhibitingNF-κB and MAPKs, as well as downstream target genes such as MMP-9.

oncology reports

Methanol extract of Hydroclathrus clathratus suppresses matrix metalloproteinase-9 in T24 bladder carcinoma cells by suppressing the NF-κB and MAPK pathways