Evaluation of Anti-invasion Effect of Resveratrol and Related Methoxy Analogues on Human Hepatocarcinoma Cells

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• 作者：Chia-Jui Weng ; Cheng-Feng Wu ; Hsiao-Wen Huang ; Chi-Hao Wu ; Chi-Tang Ho ; Gow-Chin Yen
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2010
• 出版时间：March 10, 2010
• 年：2010
• 卷：58
• 期：5
• 页码：2886-2894
• 全文大小：1120K
• 年卷期：v.58,no.5(March 10, 2010)
• ISSN：1520-5118

文摘

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-trans-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 post-translational level for TIMP-1.