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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\u0027s 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. 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Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells
http://hdl.handle.net/10069/30196
http://hdl.handle.net/10069/30196f550f11f-79d1-4841-92b8-b7c8b9c84d93
名前 / ファイル | ライセンス | アクション |
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JouGas47_195.pdf (428.9 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-01-09 | |||||
タイトル | ||||||
タイトル | Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | GGA | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | HCV | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Interferon | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | MTOR | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | STAT-1 | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Takeshita, Shigeyuki
× 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 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
書誌情報 |
Journal of Gastroenterology 巻 47, 号 2, p. 195-202, 発行日 2012-02 |
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出版者 | ||||||
出版者 | 日本消化器病学会 | |||||
出版者別言語 | ||||||
The Japanese Society of Gastroenterology | ||||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 09441174 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 14355922 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1007/s00535-011-0481-z | |||||
権利 | ||||||
権利情報 | © The Japanese Society of Gastroenterology. All rights reserved. | |||||
権利 | ||||||
権利情報 | The final publication is available at www.springerlink.com. | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal of Gastroenterology, 47(2), pp.195-202; 2012 |