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The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation

BACKGROUND: The mortality and morbidity rates from cancer metastasis have not declined in Taiwan, especially because of hepatocellular carcinoma (HCC). Resveratrol has been shown to have benefits such as cardioprotection, providing antioxidative, anti-inflammatory, anti-cancer properties in previous...

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Autores principales: Yeh, Chao-Bin, Hsieh, Ming-Ju, Lin, Chiao-Wen, Chiou, Hui-Ling, Lin, Pen-Yuan, Chen, Tzy-Yen, Yang, Shun-Fa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577687/
https://www.ncbi.nlm.nih.gov/pubmed/23437203
http://dx.doi.org/10.1371/journal.pone.0056661
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author Yeh, Chao-Bin
Hsieh, Ming-Ju
Lin, Chiao-Wen
Chiou, Hui-Ling
Lin, Pen-Yuan
Chen, Tzy-Yen
Yang, Shun-Fa
author_facet Yeh, Chao-Bin
Hsieh, Ming-Ju
Lin, Chiao-Wen
Chiou, Hui-Ling
Lin, Pen-Yuan
Chen, Tzy-Yen
Yang, Shun-Fa
author_sort Yeh, Chao-Bin
collection PubMed
description BACKGROUND: The mortality and morbidity rates from cancer metastasis have not declined in Taiwan, especially because of hepatocellular carcinoma (HCC). Resveratrol has been shown to have benefits such as cardioprotection, providing antioxidative, anti-inflammatory, anti-cancer properties in previous studies. Therefore, HCC cells were subjected to treatment with resveratrol and then analyzed to determine the effects of resveratrol on the migration and invasion. METHODOLOGY AND PRINCIPAL FINDINGS: Modified Boyden chamber assays revealed that resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 µM. The results of casein zymography and western blotting revealed that the activities and protein levels of the urokinase-type plasminogen activator (u-PA) were inhibited by resveratrol. Western blot analysis also showed that resveratrol inhibits phosphorylation of JNK1/2. Tests of the mRNA level, real-time PCR, and promoter assays evaluated the inhibitory effects of resveratrol on u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay showed that reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol. CONCLUSIONS: Resveratrol inhibits u-PA expression and the metastasis of HCC cells and is a powerful chemopreventive agent. The inhibitory effects were associated with the downregulation of the transcription factors of SP-1 signaling pathways.
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spelling pubmed-35776872013-02-22 The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation Yeh, Chao-Bin Hsieh, Ming-Ju Lin, Chiao-Wen Chiou, Hui-Ling Lin, Pen-Yuan Chen, Tzy-Yen Yang, Shun-Fa PLoS One Research Article BACKGROUND: The mortality and morbidity rates from cancer metastasis have not declined in Taiwan, especially because of hepatocellular carcinoma (HCC). Resveratrol has been shown to have benefits such as cardioprotection, providing antioxidative, anti-inflammatory, anti-cancer properties in previous studies. Therefore, HCC cells were subjected to treatment with resveratrol and then analyzed to determine the effects of resveratrol on the migration and invasion. METHODOLOGY AND PRINCIPAL FINDINGS: Modified Boyden chamber assays revealed that resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 µM. The results of casein zymography and western blotting revealed that the activities and protein levels of the urokinase-type plasminogen activator (u-PA) were inhibited by resveratrol. Western blot analysis also showed that resveratrol inhibits phosphorylation of JNK1/2. Tests of the mRNA level, real-time PCR, and promoter assays evaluated the inhibitory effects of resveratrol on u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay showed that reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol. CONCLUSIONS: Resveratrol inhibits u-PA expression and the metastasis of HCC cells and is a powerful chemopreventive agent. The inhibitory effects were associated with the downregulation of the transcription factors of SP-1 signaling pathways. Public Library of Science 2013-02-20 /pmc/articles/PMC3577687/ /pubmed/23437203 http://dx.doi.org/10.1371/journal.pone.0056661 Text en © 2013 Yeh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yeh, Chao-Bin
Hsieh, Ming-Ju
Lin, Chiao-Wen
Chiou, Hui-Ling
Lin, Pen-Yuan
Chen, Tzy-Yen
Yang, Shun-Fa
The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation
title The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation
title_full The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation
title_fullStr The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation
title_full_unstemmed The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation
title_short The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation
title_sort antimetastatic effects of resveratrol on hepatocellular carcinoma through the downregulation of a metastasis-associated protease by sp-1 modulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577687/
https://www.ncbi.nlm.nih.gov/pubmed/23437203
http://dx.doi.org/10.1371/journal.pone.0056661
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