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.
Article: Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway.[show abstract] [hide abstract]
ABSTRACT: Piceatannol has potent anti-inflammatory, immunomodulatory, anticancer and antiproliferative effects. However, little is known about the mechanism by which piceatannol inhibits invasion and metastasis. The aim of the current study was to investigate the effects of piceatannol on the expression of matrix metalloproteinase-9 (MMP-9) in DU145 human prostate cancer cells. The results revealed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α (TNF-α). However, treatment with piceatannol reversed TNF-α- and MMP-9-induced gelatin zymography and its gene expression. In addition, a Matrigel invasion assay determined that piceatannol reduces the TNF-α-induced invasion of DU145 cells. Nuclear factor-κ B (NF-κB) is a significant transcription factor that regulates numerous genes involved in tumor cell invasion and metastasis. Therefore, whether piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed. The results revealed that piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity. Using a specific NF-κB inhibitor, pyrrolidine dithiocarbamate, it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation. Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits. Furthermore, TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of piceatannol. The Akt inhibitor LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression. Overall, these data suggest that piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145 prostate cancer cells.Oncology letters 01/2013; 5(1):341-347. · 0.11 Impact Factor