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Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells


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Title: Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells
Authors: Takeshita, Shigeyuki / Ichikawa, Tatsuki / Taura, Naota / Miyaaki, Hisamitsu / Matsuzaki, Toshihisa / Otani, Masashi / Muraoka, Toru / Akiyama, Motohisa / Miuma, Satoshi / Ozawa, Eisuke / Ikeda, Masanori / Kato, Nobuyuki / Isomoto, Hajime / Takeshima, Fuminao / Nakao, Kazuhiko
Issue Date: Feb-2012
Publisher: 日本消化器病学会 / The Japanese Society of Gastroenterology
Citation: Journal of Gastroenterology, 47(2), pp.195-202; 2012
Abstract: Background Geranylgeranylacetone (GGA), an isoprenoid compound which includes retinoids, has been used orally as an anti-ulcer drug in Japan. GGA acts as a potent inducer of anti-viral gene expression by stimulating ISGF3 formation in human hepatoma cells. This drug has few side effects and reinforces the effect of IFN when administered in combination with peg-IFN and ribavirin. This study verified the anti-HCV activity of GGA in a replicon system. In addition, mechanisms of anti-HCV activity were examined in the replicon cells. Methods OR6 cells stably harboring the full-length genotype 1 replicon containing the Renilla luciferase gene, ORN/C-5B/KE, were used to examine the influence of the anti-HCV effect of GGA. After treatment, the cells were harvested with Renilla lysis reagent and then subjected to a luciferase assay according to the manufacturer's protocol. Result The results showed that GGA had anti-HCV activity. GGA induced anti-HCV replicon activity in a time- and dose-dependent manner. GGA did not activate the tyrosine 701 and serine 727 on STAT-1, and did not induce HSP-70 in OR6 cells. The anti-HCV effect depended on the GGA induced mTOR activity, not STAT-1 activity and PKR. An additive effect was observed with a combination of IFN and GGA. Conclusions GGA has mTOR dependent anti-HCV activity. There is a possibility that the GGA anti-HCV activity can be complimented by IFN. It will be necessary to examine the clinical effectiveness of the combination of GGA and IFN for HCV patients in the future.
Keywords: GGA / HCV / Interferon / MTOR / STAT-1
URI: http://hdl.handle.net/10069/30196
ISSN: 09441174
DOI: 10.1007/s00535-011-0481-z
Rights: © The Japanese Society of Gastroenterology. All rights reserved. / The final publication is available at www.springerlink.com.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/30196

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