Hispolon suppresses SK-Hep1 human hepatoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and ERK signaling pathways

Guan Jhong Huang, Chih Min Yang, Yuan Shiun Chang, Sakae Amagaya, Hsiao Chieh Wang, Wen Chi Hou, Shyh Shyun Huang, Miao Lin Hu

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Cancer metastasis is a primary cause of cancer death. Hispolon is an active phenolic compound of Phellinus linteus, a mushroom that has recently been shown to have antioxidant and anticancer activities. In this study, we first observed that hispolon exerted a dose-dependent inhibitory effect on invasion and motility, but not on adhesion, of the highly metastatic SK-Hep1 cells in the absence of cytotoxicity. Mechanistically, hispolon decreased the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-plasminogen activator (uPA) in a concentration-dependent manner. Hispolon also inhibited phosphorylation of extracellular signaling-regulating kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase/serine/threonine protein kinase (or protein kinase B (PI3K/Akt), and focal adhesion kinase (FAK). Furthermore, treatment of SK-Hep1 cells with an inhibitor specific for ERK1/2 (PD98256) decreased the expression of MMP-2, and MMP-9. These results demonstrate that hispolon can inhibit the metastasis of SK-Hep1 cells by reduced expression of MMP-2, MMP-9, and uPA through the suppression of the FAK signaling pathway and of the activity of PI3K/Akt and Ras homologue gene family, member A (RhoA). These findings suggest that hispolon may be used as an antimetastatic agent.

Original languageEnglish
Pages (from-to)9468-9475
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Issue number17
Publication statusPublished - Sep 8 2010



  • Hispolon
  • MMP-2
  • MMP-9
  • Phellinus linteus
  • uPA

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

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