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

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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
Volume58
Issue number17
DOIs
Publication statusPublished - Sep 8 2010

Fingerprint

u-plasminogen activator
gelatinase A
gelatinase B
MAP Kinase Signaling System
Plasminogen Activators
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Urokinase-Type Plasminogen Activator
phosphatidylinositol 3-kinase
non-specific protein-tyrosine kinase
hepatoma
Phosphatidylinositol 3-Kinases
mitogen-activated protein kinase
metastasis
Hepatocellular Carcinoma
Neoplasm Metastasis
Phellinus linteus
Focal Adhesion Protein-Tyrosine Kinases
neoplasms
cells

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Journal of Agricultural and Food Chemistry, Vol. 58, No. 17, 08.09.2010, p. 9468-9475.

Research output: Contribution to journalArticle

Huang, Guan Jhong ; Yang, Chih Min ; Chang, Yuan Shiun ; Amagaya, Sakae ; Wang, Hsiao Chieh ; Hou, Wen Chi ; Huang, Shyh Shyun ; Hu, Miao Lin. / 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. In: Journal of Agricultural and Food Chemistry. 2010 ; Vol. 58, No. 17. pp. 9468-9475.
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AU - Huang, Guan Jhong

AU - Yang, Chih Min

AU - Chang, Yuan Shiun

AU - Amagaya, Sakae

AU - Wang, Hsiao Chieh

AU - Hou, Wen Chi

AU - Huang, Shyh Shyun

AU - Hu, Miao Lin

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