Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells

Chia Jui Weng, Cheng Feng Wu, Hsiao Wen Huang, Chi Hao Wu, Chi Tang Ho, Gow Chin Yen

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is also highly metastatic. Metastasis is considered to be the major cause of death in cancer patients. Resveratrol (3,5,4'-trihydroxystilbene) and related analogues have been reported as candidates to prevent cancer growth and invasion. The bioactivity of resveratrol-related analogues could be altered due to the presence and positioning of methoxy groups on the basic resveratrol chemical structure. This study investigated the effects and mechanism of action of resveratrol and its methoxy analogues on invasion of human hepatocarcinoma cells. The migratory and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by treatment with resveratrol and 3,5,4'-trimethoxy-frans- stilbene (MR-3). Upon incubation of PMA-treated HepG2 cells with resveratrol (0-50 μM) or MR-3 (0-50 μM), the MMP-9 activity decreased but TIMP-1 protein increased in a dose-dependent manner. With resveratrol (0-50 μM) or MR-3 (0-1 μM) treatment on PMA-untreated Hep3B cells, both of the MMP-9 and MMP-2 activities decreased but TIMP-2 protein increased in a dose-dependent manner. These results suggest that resveratrol and its related methoxy analogue MR-3 might exert anti-invasive activity against hepatoma cells through regulation of MMP-2, MMP-9, TIMP-1, and TIMP-2. Further analysis with semiquantitative RT-PCR showed that the regulation of MMP-9 and TIMP-2 expressions by resveratrol and MR-3 in hepatoma cells may be on the transcriptional level but on the translational or posttranslational level for TIMP-1.

Original languageEnglish
Pages (from-to)2886-2894
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Volume58
Issue number5
DOIs
Publication statusPublished - Mar 10 2010
Externally publishedYes

Fingerprint

resveratrol
Matrix Metalloproteinases
gelatinase B
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
cells
hepatoma
acetates
Acetates
gelatinase A
Tissue Inhibitor of Metalloproteinases
Hepatocellular Carcinoma
dosage
neoplasms
stilbenes
liver neoplasms
Stilbenes
Hep G2 Cells
metastasis
chemical structure

Keywords

  • Invasion
  • MMPs
  • MR-3
  • Resveratrol
  • TIMPs
  • uPA

ASJC Scopus subject areas

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

Cite this

Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells. / Weng, Chia Jui; Wu, Cheng Feng; Huang, Hsiao Wen; Wu, Chi Hao; Ho, Chi Tang; Yen, Gow Chin.

In: Journal of Agricultural and Food Chemistry, Vol. 58, No. 5, 10.03.2010, p. 2886-2894.

Research output: Contribution to journalArticle

Weng, Chia Jui ; Wu, Cheng Feng ; Huang, Hsiao Wen ; Wu, Chi Hao ; Ho, Chi Tang ; Yen, Gow Chin. / Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells. In: Journal of Agricultural and Food Chemistry. 2010 ; Vol. 58, No. 5. pp. 2886-2894.
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AU - Ho, Chi Tang

AU - Yen, Gow Chin

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AB - Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is also highly metastatic. Metastasis is considered to be the major cause of death in cancer patients. Resveratrol (3,5,4'-trihydroxystilbene) and related analogues have been reported as candidates to prevent cancer growth and invasion. The bioactivity of resveratrol-related analogues could be altered due to the presence and positioning of methoxy groups on the basic resveratrol chemical structure. This study investigated the effects and mechanism of action of resveratrol and its methoxy analogues on invasion of human hepatocarcinoma cells. The migratory and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by treatment with resveratrol and 3,5,4'-trimethoxy-frans- stilbene (MR-3). Upon incubation of PMA-treated HepG2 cells with resveratrol (0-50 μM) or MR-3 (0-50 μM), the MMP-9 activity decreased but TIMP-1 protein increased in a dose-dependent manner. With resveratrol (0-50 μM) or MR-3 (0-1 μM) treatment on PMA-untreated Hep3B cells, both of the MMP-9 and MMP-2 activities decreased but TIMP-2 protein increased in a dose-dependent manner. These results suggest that resveratrol and its related methoxy analogue MR-3 might exert anti-invasive activity against hepatoma cells through regulation of MMP-2, MMP-9, TIMP-1, and TIMP-2. Further analysis with semiquantitative RT-PCR showed that the regulation of MMP-9 and TIMP-2 expressions by resveratrol and MR-3 in hepatoma cells may be on the transcriptional level but on the translational or posttranslational level for TIMP-1.

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