Inhibitory effect of luteolin on hepatocyte growth factor/scatter factor-induced HepG2 cell invasion involving both MAPK/ERKs and PI3K-Akt pathways

Wei Jiunn Lee, Lan Feng Wu, Wen Kang Chen, Chau Jong Wang, Tsui Hwa Tseng

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Hepatocyte growth factor (HGF), also known as scatter factor (SF), and its receptor, the c-Met tyrosine kinase, play roles in cancer invasion and metastasis in a wide variety of tumor cells. Clinical observations suggest that HGF can promote metastasis of hepatoma cells while stimulating tumor invasiveness. We use HGF as an invasive inducer of human hepatoma HepG2 cells to investigate the effect of flavonoids on anti-invasion. In our preliminary study, we investigated the effect of flavonoids including luteolin, quercetin, baicalein, genistein, taxifolin and catechin on HGF-mediated migration and invasion of HepG2 cells. We found that luteolin presented the most potent potential on anti-migration and anti-invasion by Boyden chamber assay. Furthermore, luteolin inhibited HGF-induced cell scattering and cytoskeleton change such as filopodia and lamellipodia was determined by both phase-contrast and fluorescence microscopy studies. In addition, Western blotting and immunoprecipitation were performed to confirm luteolin suppressed the phosphorylation of c-Met, the membrane receptor of HGF, as well as ERK1/2 and Akt, but not JNK1/2, which is activated by HGF. Our investigation demonstrated that luteolin similar to PD98059, which acts as a specific inhibitor of MEK, an up stream kinase regulating ERK1/2, and wortmannin, a PI3K inhibitor, inhibited the invasiveness induced by HGF. In conclusion, the luteolin inhibited HGF-induced HepG2 cell invasion involving both MAPK/ERKs and PI3K-Akt pathways.

Original languageEnglish
Pages (from-to)123-133
Number of pages11
JournalChemico-Biological Interactions
Volume160
Issue number2
DOIs
Publication statusPublished - Mar 25 2006
Externally publishedYes

Fingerprint

Luteolin
Hepatocyte Growth Factor
Hep G2 Cells
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-met
Pseudopodia
Flavonoids
Tumors
Hepatocellular Carcinoma
Neoplasm Metastasis
Phase-Contrast Microscopy
Neoplasms
Phosphorylation
Mitogen-Activated Protein Kinase 3
Catechin
Genistein
Fluorescence microscopy
Mitogen-Activated Protein Kinase Kinases
Quercetin
Cytoskeleton

Keywords

  • Akt
  • ERK
  • HepG2
  • HGF
  • Invasion
  • Luteolin

ASJC Scopus subject areas

  • Toxicology

Cite this

Inhibitory effect of luteolin on hepatocyte growth factor/scatter factor-induced HepG2 cell invasion involving both MAPK/ERKs and PI3K-Akt pathways. / Lee, Wei Jiunn; Wu, Lan Feng; Chen, Wen Kang; Wang, Chau Jong; Tseng, Tsui Hwa.

In: Chemico-Biological Interactions, Vol. 160, No. 2, 25.03.2006, p. 123-133.

Research output: Contribution to journalArticle

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abstract = "Hepatocyte growth factor (HGF), also known as scatter factor (SF), and its receptor, the c-Met tyrosine kinase, play roles in cancer invasion and metastasis in a wide variety of tumor cells. Clinical observations suggest that HGF can promote metastasis of hepatoma cells while stimulating tumor invasiveness. We use HGF as an invasive inducer of human hepatoma HepG2 cells to investigate the effect of flavonoids on anti-invasion. In our preliminary study, we investigated the effect of flavonoids including luteolin, quercetin, baicalein, genistein, taxifolin and catechin on HGF-mediated migration and invasion of HepG2 cells. We found that luteolin presented the most potent potential on anti-migration and anti-invasion by Boyden chamber assay. Furthermore, luteolin inhibited HGF-induced cell scattering and cytoskeleton change such as filopodia and lamellipodia was determined by both phase-contrast and fluorescence microscopy studies. In addition, Western blotting and immunoprecipitation were performed to confirm luteolin suppressed the phosphorylation of c-Met, the membrane receptor of HGF, as well as ERK1/2 and Akt, but not JNK1/2, which is activated by HGF. Our investigation demonstrated that luteolin similar to PD98059, which acts as a specific inhibitor of MEK, an up stream kinase regulating ERK1/2, and wortmannin, a PI3K inhibitor, inhibited the invasiveness induced by HGF. In conclusion, the luteolin inhibited HGF-induced HepG2 cell invasion involving both MAPK/ERKs and PI3K-Akt pathways.",
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