Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells

Min Hsiung Pan, Yi Siou Chiou, Wei Jen Chen, Ju-Ming Wang, Vladimir Badmaev, Chi Tang Ho

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Pterostilbene, a natural dimethylated analog of resveratrol, is known to have diverse pharmacologic activities including anticancer, anti-inflammation, antioxidant, apoptosis, anti-proliferation and analgesic potential. However, the effects of pterostilbene in preventing invasion of cancer cells have not been studied. Here, we report our finding that pterostilbene significantly suppressed 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced invasion, migration and metastasis of human hepatoma cells (HepG 2 cells). Increase in the enzyme activity, protein and messenger RNA levels of matrix metalloproteinase (MMP)-9 were observed in TPA-treated HepG 2 cells, and these were blocked by pterostilbene. In addition, pterostilbene can inhibit TPA-induced expression of vascular endothelial growth factor, epidermal growth factor and epidermal growth factor receptor. Transient transfection experiments also showed that pterostilbene strongly inhibited TPA-stimulated nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1)-dependent transcriptional activity in HepG 2 cells. Moreover, pterostilbene can suppress TPA-induced activation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, c-Jun N-terminal kinases 1/2 and phosphatidylinositol 3-kinase/Akt and protein kinase C that are upstream of NF-κB and AP-1. Significant therapeutic effects were further demonstrated in vivo by treating nude mice with pterostilbene (50 and 250 mg/kg intraperitoneally) after inoculation with HepG 2 cells into the tail vein. Presented data reveal that pterostilbene is a novel, effective, anti-metastatic agent that functions by downregulating MMP-9 gene expression.

Original languageEnglish
Pages (from-to)1234-1242
Number of pages9
JournalCarcinogenesis
Volume30
Issue number7
DOIs
Publication statusPublished - 2009 Jul 15

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Hepatocellular Carcinoma
Signal Transduction
Tetradecanoylphorbol Acetate
Neoplasms
NF-kappa B
Matrix Metalloproteinase 9
Transcription Factor AP-1
Mitogen-Activated Protein Kinase 9
Mitogen-Activated Protein Kinase 8
Phosphatidylinositol 3-Kinase
pterostilbene
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Therapeutic Uses
p38 Mitogen-Activated Protein Kinases
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Nude Mice
Protein Kinase C
Vascular Endothelial Growth Factor A

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Pan, Min Hsiung ; Chiou, Yi Siou ; Chen, Wei Jen ; Wang, Ju-Ming ; Badmaev, Vladimir ; Ho, Chi Tang. / Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. In: Carcinogenesis. 2009 ; Vol. 30, No. 7. pp. 1234-1242.
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Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. / Pan, Min Hsiung; Chiou, Yi Siou; Chen, Wei Jen; Wang, Ju-Ming; Badmaev, Vladimir; Ho, Chi Tang.

In: Carcinogenesis, Vol. 30, No. 7, 15.07.2009, p. 1234-1242.

Research output: Contribution to journalArticle

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AU - Wang, Ju-Ming

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AU - Ho, Chi Tang

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