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.