ID | 34245 |
FullText URL | |
Author |
Matsumoto, Yohsuke
Motoki, Takahiro
Tsubouchi, Hirohito
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Abstract | Hepatocyte growth factor (HGF), which is produced by surrounding stromal cells, including fibroblasts and endothelial cells, has been shown to be a significant factor responsible for cancer cell invasion mediated by tumor-stromal interactions. We found in this study that the anti-tumor agent valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, strongly inhibited tumor-stromal interaction. VPA inhibited HGF production in fibroblasts induced by epidermal growth factor (EGF), platelet-derived growth factor, basic fibroblast growth factor, phorbol 12-myristate 13-acetate (PMA) and prostaglandin E-2 without any appreciable cytotoxic effect. Other HDAC inhibitors, including butyric acid and trichostatin A (TSA), showed similar inhibitory effects on HGF production stimulated by various inducers. Up-regulations of HGF gene expression induced by PMA and EGF were also suppressed by VPA and TSA. Furthermore, VPA significantly inhibited HGF-induced invasion of HepG2 hepatocellular carcinoma cells. VPA, however, did not affect the increases in phosphorylation of MAPK and Akt in HGF-treated HepG2 cells. These results demonstrated that VPA inhibited two critical processes of tumor-stromal interaction, induction of fibroblastic HGF production and HGF-induced invasion of HepG2 cells, and suggest that those activities serve for other anti-tumor mechanisms of VPA besides causing proliferation arrest, differentiation, and/or apoptosis of tumor cells.
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Keywords | hepatocyte growth factor
valproic acid
histone deacetylase inhibitor
butyric acid
trichostatin A
induction
tumor invasion
dermal fibroblast
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Note | Published with permission from the copyright holder.
This is a author's copy,as published in Biochemical and Biophysical Research Communications, 2008 Vol.366 Issue.1 pp.110-116 |
Published Date | 2008-02-01
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Publication Title |
Biochemical and Biophysical Research Communications
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Volume | volume366
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Issue | issue1
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Publisher | Academic Press
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Start Page | 110
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End Page | 116
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ISSN | 0006-291X
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NCID | AA00564395
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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File Version | author
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PubMed ID | |
DOI | |
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