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Suppression of Hepatitis B Virus X Protein-Mediated Tumorigenic Effects by Ursolic Acid
This study investigated the potential effects of natural products ursolic acid (UA) and oleanolic acid (OA) against HBx-mediated tumorigenic activities in vitro and in vivo. HBx transactivated Sp-1 and Smad 3/4 in Huh7 and FL83B hepatocytes and induced cell migration of Huh7 and HepG2. HBx also indu...
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| Published in: | Journal of agricultural and food chemistry 2011-03, Vol.59 (5), p.1713-1722 |
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| Main Authors: | , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-a368t-3b5128e80f551d8c73fd64204a1b0ae3bd74286f4e093f148bfab4c3d7f5c0543 |
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| cites | cdi_FETCH-LOGICAL-a368t-3b5128e80f551d8c73fd64204a1b0ae3bd74286f4e093f148bfab4c3d7f5c0543 |
| container_end_page | 1722 |
| container_issue | 5 |
| container_start_page | 1713 |
| container_title | Journal of agricultural and food chemistry |
| container_volume | 59 |
| creator | Wu, Hong-Yin Chang, Chi-I Lin, Bo-Wei Yu, Feng-Ling Lin, Ping-Yuan Hsu, Jue-Liang Yen, Chia-Hung Liao, Ming-Huei Shih, Wen-Ling |
| description | This study investigated the potential effects of natural products ursolic acid (UA) and oleanolic acid (OA) against HBx-mediated tumorigenic activities in vitro and in vivo. HBx transactivated Sp-1 and Smad 3/4 in Huh7 and FL83B hepatocytes and induced cell migration of Huh7 and HepG2. HBx also induced MMP-3 secretion in Huh7 and acted against TGF-β-induced apoptosis in Hep3B. UA almost completely blocked the HBx-mediated effects, while OA had a partial inhibitive effect. Utilization of specific MAPK inhibitors and immunoblotting demonstrated that UA selectively activated MAPK signaling in certain tested cells. Preintraperitoneal injection of UA fully prevented the tumor growth of HBV-containing 2.2.15 cells, while OA-treated mice had smaller tumors than the control group. Our results suggested that UA possesses a hepatoprotective ability and illustrated the evident effects against HBx-mediated tumorigenic activities without toxicity in a mouse model. |
| doi_str_mv | 10.1021/jf1045624 |
| format | article |
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HBx transactivated Sp-1 and Smad 3/4 in Huh7 and FL83B hepatocytes and induced cell migration of Huh7 and HepG2. HBx also induced MMP-3 secretion in Huh7 and acted against TGF-β-induced apoptosis in Hep3B. UA almost completely blocked the HBx-mediated effects, while OA had a partial inhibitive effect. Utilization of specific MAPK inhibitors and immunoblotting demonstrated that UA selectively activated MAPK signaling in certain tested cells. Preintraperitoneal injection of UA fully prevented the tumor growth of HBV-containing 2.2.15 cells, while OA-treated mice had smaller tumors than the control group. Our results suggested that UA possesses a hepatoprotective ability and illustrated the evident effects against HBx-mediated tumorigenic activities without toxicity in a mouse model.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/jf1045624</identifier><identifier>PMID: 21314126</identifier><identifier>CODEN: JAFCAU</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject><![CDATA[animal models ; Animals ; Antineoplastic Agents, Phytogenic - administration & dosage ; apoptosis ; Bioactive Constituents ; Biological and medical sciences ; Carcinoma, Hepatocellular ; Cell Division - drug effects ; Cell Line ; Cell Line, Tumor ; cell movement ; Flavones - administration & dosage ; Food industries ; Fundamental and applied biological sciences. Psychology ; Hepatitis B virus ; hepatocytes ; Hepatocytes - drug effects ; Humans ; immunoblotting ; Liver Neoplasms - chemically induced ; Liver Neoplasms - prevention & control ; Mice ; Mice, Nude ; mitogen-activated protein kinase ; Mitogen-Activated Protein Kinases - metabolism ; Neoplasm Transplantation ; neoplasms ; oleanolic acid ; Oleanolic Acid - administration & dosage ; secretion ; Signal Transduction ; toxicity ; Trans-Activators - antagonists & inhibitors ; Trans-Activators - genetics ; Trans-Activators - pharmacology ; Transcriptional Activation - drug effects ; Transfection ; Triterpenes - administration & dosage ; Ursolic Acid ; Viral Regulatory and Accessory Proteins]]></subject><ispartof>Journal of agricultural and food chemistry, 2011-03, Vol.59 (5), p.1713-1722</ispartof><rights>Copyright © 2011 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a368t-3b5128e80f551d8c73fd64204a1b0ae3bd74286f4e093f148bfab4c3d7f5c0543</citedby><cites>FETCH-LOGICAL-a368t-3b5128e80f551d8c73fd64204a1b0ae3bd74286f4e093f148bfab4c3d7f5c0543</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23915923$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21314126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Hong-Yin</creatorcontrib><creatorcontrib>Chang, Chi-I</creatorcontrib><creatorcontrib>Lin, Bo-Wei</creatorcontrib><creatorcontrib>Yu, Feng-Ling</creatorcontrib><creatorcontrib>Lin, Ping-Yuan</creatorcontrib><creatorcontrib>Hsu, Jue-Liang</creatorcontrib><creatorcontrib>Yen, Chia-Hung</creatorcontrib><creatorcontrib>Liao, Ming-Huei</creatorcontrib><creatorcontrib>Shih, Wen-Ling</creatorcontrib><title>Suppression of Hepatitis B Virus X Protein-Mediated Tumorigenic Effects by Ursolic Acid</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>This study investigated the potential effects of natural products ursolic acid (UA) and oleanolic acid (OA) against HBx-mediated tumorigenic activities in vitro and in vivo. HBx transactivated Sp-1 and Smad 3/4 in Huh7 and FL83B hepatocytes and induced cell migration of Huh7 and HepG2. HBx also induced MMP-3 secretion in Huh7 and acted against TGF-β-induced apoptosis in Hep3B. UA almost completely blocked the HBx-mediated effects, while OA had a partial inhibitive effect. Utilization of specific MAPK inhibitors and immunoblotting demonstrated that UA selectively activated MAPK signaling in certain tested cells. Preintraperitoneal injection of UA fully prevented the tumor growth of HBV-containing 2.2.15 cells, while OA-treated mice had smaller tumors than the control group. Our results suggested that UA possesses a hepatoprotective ability and illustrated the evident effects against HBx-mediated tumorigenic activities without toxicity in a mouse model.</description><subject>animal models</subject><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - administration & dosage</subject><subject>apoptosis</subject><subject>Bioactive Constituents</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular</subject><subject>Cell Division - drug effects</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>cell movement</subject><subject>Flavones - administration & dosage</subject><subject>Food industries</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hepatitis B virus</subject><subject>hepatocytes</subject><subject>Hepatocytes - drug effects</subject><subject>Humans</subject><subject>immunoblotting</subject><subject>Liver Neoplasms - chemically induced</subject><subject>Liver Neoplasms - prevention & control</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>mitogen-activated protein kinase</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Neoplasm Transplantation</subject><subject>neoplasms</subject><subject>oleanolic acid</subject><subject>Oleanolic Acid - administration & dosage</subject><subject>secretion</subject><subject>Signal Transduction</subject><subject>toxicity</subject><subject>Trans-Activators - antagonists & inhibitors</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - pharmacology</subject><subject>Transcriptional Activation - drug effects</subject><subject>Transfection</subject><subject>Triterpenes - administration & dosage</subject><subject>Ursolic Acid</subject><subject>Viral Regulatory and Accessory Proteins</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNpt0DtPwzAQwHELgWh5DHwB8MLAELjzI3FGQLwkEEhtgS1yHBu5apPIToZ-e4Ja6MJk6fzT6fQn5AThEoHh1dwhCJkysUPGKBkkElHtkjEMn4mSKY7IQYxzAFAyg30yYshRIEvH5GPSt22wMfqmpo2jj7bVne98pDf03Yc-0k_6FprO-jp5sZXXna3otF82wX_Z2ht655w1XaTlis5CbBbD6Nr46ojsOb2I9njzHpLZ_d309jF5fn14ur1-TjRPVZfwUiJTVoGTEitlMu6qVDAQGkvQlpdVJphKnbCQc4dClU6XwvAqc9KAFPyQXKz3mtDEGKwr2uCXOqwKhOInTvEXZ7Cna9v25dJWf_K3xgDON0BHoxcu6Nr4uHU8R5kzPriztXO6KfRXGMxswgDFUDiXwPl2kzaxmDd9qIcI_5z0DcYef-s</recordid><startdate>20110309</startdate><enddate>20110309</enddate><creator>Wu, Hong-Yin</creator><creator>Chang, Chi-I</creator><creator>Lin, Bo-Wei</creator><creator>Yu, Feng-Ling</creator><creator>Lin, Ping-Yuan</creator><creator>Hsu, Jue-Liang</creator><creator>Yen, Chia-Hung</creator><creator>Liao, Ming-Huei</creator><creator>Shih, Wen-Ling</creator><general>American Chemical Society</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20110309</creationdate><title>Suppression of Hepatitis B Virus X Protein-Mediated Tumorigenic Effects by Ursolic Acid</title><author>Wu, Hong-Yin ; Chang, Chi-I ; Lin, Bo-Wei ; Yu, Feng-Ling ; Lin, Ping-Yuan ; Hsu, Jue-Liang ; Yen, Chia-Hung ; Liao, Ming-Huei ; Shih, Wen-Ling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a368t-3b5128e80f551d8c73fd64204a1b0ae3bd74286f4e093f148bfab4c3d7f5c0543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>animal models</topic><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - administration & dosage</topic><topic>apoptosis</topic><topic>Bioactive Constituents</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular</topic><topic>Cell Division - drug effects</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>cell movement</topic><topic>Flavones - administration & dosage</topic><topic>Food industries</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hepatitis B virus</topic><topic>hepatocytes</topic><topic>Hepatocytes - drug effects</topic><topic>Humans</topic><topic>immunoblotting</topic><topic>Liver Neoplasms - chemically induced</topic><topic>Liver Neoplasms - prevention & control</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>mitogen-activated protein kinase</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Neoplasm Transplantation</topic><topic>neoplasms</topic><topic>oleanolic acid</topic><topic>Oleanolic Acid - administration & dosage</topic><topic>secretion</topic><topic>Signal Transduction</topic><topic>toxicity</topic><topic>Trans-Activators - antagonists & inhibitors</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - pharmacology</topic><topic>Transcriptional Activation - drug effects</topic><topic>Transfection</topic><topic>Triterpenes - administration & dosage</topic><topic>Ursolic Acid</topic><topic>Viral Regulatory and Accessory Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Hong-Yin</creatorcontrib><creatorcontrib>Chang, Chi-I</creatorcontrib><creatorcontrib>Lin, Bo-Wei</creatorcontrib><creatorcontrib>Yu, Feng-Ling</creatorcontrib><creatorcontrib>Lin, Ping-Yuan</creatorcontrib><creatorcontrib>Hsu, Jue-Liang</creatorcontrib><creatorcontrib>Yen, Chia-Hung</creatorcontrib><creatorcontrib>Liao, Ming-Huei</creatorcontrib><creatorcontrib>Shih, Wen-Ling</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Hong-Yin</au><au>Chang, Chi-I</au><au>Lin, Bo-Wei</au><au>Yu, Feng-Ling</au><au>Lin, Ping-Yuan</au><au>Hsu, Jue-Liang</au><au>Yen, Chia-Hung</au><au>Liao, Ming-Huei</au><au>Shih, Wen-Ling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppression of Hepatitis B Virus X Protein-Mediated Tumorigenic Effects by Ursolic Acid</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2011-03-09</date><risdate>2011</risdate><volume>59</volume><issue>5</issue><spage>1713</spage><epage>1722</epage><pages>1713-1722</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><coden>JAFCAU</coden><abstract>This study investigated the potential effects of natural products ursolic acid (UA) and oleanolic acid (OA) against HBx-mediated tumorigenic activities in vitro and in vivo. HBx transactivated Sp-1 and Smad 3/4 in Huh7 and FL83B hepatocytes and induced cell migration of Huh7 and HepG2. HBx also induced MMP-3 secretion in Huh7 and acted against TGF-β-induced apoptosis in Hep3B. UA almost completely blocked the HBx-mediated effects, while OA had a partial inhibitive effect. Utilization of specific MAPK inhibitors and immunoblotting demonstrated that UA selectively activated MAPK signaling in certain tested cells. Preintraperitoneal injection of UA fully prevented the tumor growth of HBV-containing 2.2.15 cells, while OA-treated mice had smaller tumors than the control group. Our results suggested that UA possesses a hepatoprotective ability and illustrated the evident effects against HBx-mediated tumorigenic activities without toxicity in a mouse model.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>21314126</pmid><doi>10.1021/jf1045624</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-8561 |
| ispartof | Journal of agricultural and food chemistry, 2011-03, Vol.59 (5), p.1713-1722 |
| issn | 0021-8561 1520-5118 |
| language | eng |
| recordid | cdi_crossref_primary_10_1021_jf1045624 |
| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | animal models Animals Antineoplastic Agents, Phytogenic - administration & dosage apoptosis Bioactive Constituents Biological and medical sciences Carcinoma, Hepatocellular Cell Division - drug effects Cell Line Cell Line, Tumor cell movement Flavones - administration & dosage Food industries Fundamental and applied biological sciences. Psychology Hepatitis B virus hepatocytes Hepatocytes - drug effects Humans immunoblotting Liver Neoplasms - chemically induced Liver Neoplasms - prevention & control Mice Mice, Nude mitogen-activated protein kinase Mitogen-Activated Protein Kinases - metabolism Neoplasm Transplantation neoplasms oleanolic acid Oleanolic Acid - administration & dosage secretion Signal Transduction toxicity Trans-Activators - antagonists & inhibitors Trans-Activators - genetics Trans-Activators - pharmacology Transcriptional Activation - drug effects Transfection Triterpenes - administration & dosage Ursolic Acid Viral Regulatory and Accessory Proteins |
| title | Suppression of Hepatitis B Virus X Protein-Mediated Tumorigenic Effects by Ursolic Acid |
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