The ethyl alcohol extract of Hizikia fusiforme inhibits matrix metalloproteinase activity and regulates tight junction related protein expression in Hep3B human hepatocarcinoma cells.
We tested the correlation between the tightness of tight junctions (TJs) and the anti-invasive activity of the ethyl alcohol extract of Hizikia fusiforme (EHF) in Hep3B human hepatocarcinoma cells. EHF inhibited cell proliferation, motility, and invasiveness, which were associated with increased TJ tightness, as demonstrated by an increase in transepithelial electrical resistance. EHF dose-dependently decreased the secretion of matrix metalloprotease-2 and -9, which correlated with a decrease in mRNA and protein expression, but increased tissue inhibitor of metalloproteinase-1 and -2 mRNA levels. Additionally, immunoblotting results indicated that EHF suppressed the major components of TJ, claudins (-1, -3, and -4), which play a key role in the control and selectivity of paracellular transport. These data indicate that EHF may inhibit cancer cell invasion through the tightening of TJs, which may counteract the up-regulation of claudins. Furthermore, EHF treatment decreased the expression of insulin-like growth factor-1 receptor proteins, while concurrently increasing that of thrombospondin-1 and E-cadherin. In conclusion, these results suggest that EHF treatment may inhibit tumor metastasis and invasion and therefore act as a dietary resource for decreasing the risk of developing cancer.
Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School, Busan, Republic of Korea.
Sung Ok
SO
Kim
Yung Hyun
YH
Choi
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D057167:Claudins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D000459:Phaeophyceae; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D057167:Claudins; D010936:Plant Extracts; D012333:RNA, Messenger; D019700:Thrombospondin 1; D017526:Receptor, IGF Type 1; D020782:Matrix Metalloproteinases