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KMID : 0603520010060040232
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Journal of Korean Association of Cancer Prevention
2001 Volume.6 No. 4 p.232 ~ p.239
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The Effect of Histone Deacetylase (HDAC) Inhibitors on th Expression of Angiogenesis-related Genes
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Kim Se-Hee
Bae Myung-Ho
Jung Joo-Won
Bae Moon-Kyoung
Kwon Ho-Jeong
Yoo Mi-Ae
Kim Kyu-Won
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Abstract
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The acetylation and deacetylation of histones play significant roles in the regulation of transcription. Histone deacetylases (HDACs) are important enzymes that regulate gene transcription and alter chromatin assembly with essential and conserved functions. Function of HDACs has been focused on their transcriptional corepression of a large number of targets in chromatin remodeling processes inside nucleus. Our previous study has suggested that HDACs regulate the expression of angiogenesis-related genes. Therefore HDACs inhibitors have a potential as anti-cancer drugs, but the detailed function on their anti-angiogenic activity is not well understood. To determine the function of HDAC inhibitors in the angiogenic process, we investigated the effect of the HDAC specific inhibitors, such as trichostatin A (TSA) and FR901228, on the expression of angiogenesis-related genes, transcription factors and a tumor suppressor gene. We performed the Western blot analysis after the treatment of HepG2 human hepatoblastoma cells with TSA of FR901228. The protein levels of angiogenesis-related genes, i.e.,VEGF, MT1-MMP, Sp1,c-Jun and c-Fos and transcription factors, i.e., Egr-1 and Ets1 were decreased by TSA and FR901228. Especially FR901228 showed a stronger inhibitory activity than TSA. The protein expression of a tumor suppressor gene, i.e., gelsolin was increased by TSA and FR901228.These results suggest that HDAC inhibitors suppress the angiogenic processes through regulation of the expression of angiogenesis-related genes.
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KEYWORD
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Trichostatin A, FR901228, Histone Deacetylase inhibitor, Angiogenesis
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