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.