The protective effects of paeonol against epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice via inhibition of the PI3K/Akt/NF-kB pathway
Epirubicin is widely used for the treatment of various breast cancers; however, it has serious adverse side effects, such as hepatotoxicity, which require dose-adjustment or therapy substitution. Paeonol, an active component from Moutan Cortex, has a variety of biological activities, including preve...
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| Veröffentlicht in: | Chemico-biological interactions 2016-01, Vol.244, p.1-8 |
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| creator | Wu, Jing Xue, Xia Zhang, Bin Jiang, Wen Cao, Hongmei Wang, Rongmei Sun, Deqing Guo, Ruichen |
| description | Epirubicin is widely used for the treatment of various breast cancers; however, it has serious adverse side effects, such as hepatotoxicity, which require dose-adjustment or therapy substitution. Paeonol, an active component from Moutan Cortex, has a variety of biological activities, including preventing or reducing various toxicities induced by antineoplastics. Protection by paeonol against hepatotoxicity induced by epirubicin and the underlying mechanism of action were investigated in this study. Cytosolic enzymes in the serum and oxidative stress indices in the liver were determined. The protective effects were determined using the MTT assay in vitro or by evaluating the expression of apoptotic factors and crucial proteins in the PI3K/Akt/NF-kB pathway using western blot analysis. It is concluded that paeonol alleviates epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice by inhibiting the PI3K/Akt/NF-kB pathway.
•Epirubicin is widely used to treat breast cancer, but limited for its hepatotoxicity.•Paeonol could alleviate epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice.•The mechanism relies on inhibiting the PI3K/Akt/NF-kB pathway. |
| doi_str_mv | 10.1016/j.cbi.2015.11.025 |
| format | Article |
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•Epirubicin is widely used to treat breast cancer, but limited for its hepatotoxicity.•Paeonol could alleviate epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice.•The mechanism relies on inhibiting the PI3K/Akt/NF-kB pathway.</description><identifier>ISSN: 0009-2797</identifier><identifier>EISSN: 1872-7786</identifier><identifier>DOI: 10.1016/j.cbi.2015.11.025</identifier><identifier>PMID: 26646421</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Acetophenones - pharmacology ; Animals ; Breast cancer ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Chemical and Drug Induced Liver Injury - complications ; Chemical and Drug Induced Liver Injury - drug therapy ; Chemical and Drug Induced Liver Injury - metabolism ; Chemical and Drug Induced Liver Injury - prevention & control ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Drugs, Chinese Herbal - chemistry ; Epirubicin ; Epirubicin - adverse effects ; Female ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; Hepatocytes - pathology ; Hepatotoxicity ; Mammary Neoplasms, Experimental - complications ; Mammary Neoplasms, Experimental - drug therapy ; Mice ; NF-kappa B - metabolism ; Oxidative Stress - drug effects ; Paeonia - chemistry ; Paeonol ; Phosphatidylinositol 3-Kinases - metabolism ; PI3K/Akt/NF-kB ; Protective Agents - pharmacology ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction - drug effects ; Structure-Activity Relationship</subject><ispartof>Chemico-biological interactions, 2016-01, Vol.244, p.1-8</ispartof><rights>2015 Elsevier Ireland Ltd</rights><rights>Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-c01c1c3b36e4cb513678d9fee374d05480103bd9e84fe85df4211b458aa147ed3</citedby><cites>FETCH-LOGICAL-c452t-c01c1c3b36e4cb513678d9fee374d05480103bd9e84fe85df4211b458aa147ed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cbi.2015.11.025$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26646421$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Jing</creatorcontrib><creatorcontrib>Xue, Xia</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Jiang, Wen</creatorcontrib><creatorcontrib>Cao, Hongmei</creatorcontrib><creatorcontrib>Wang, Rongmei</creatorcontrib><creatorcontrib>Sun, Deqing</creatorcontrib><creatorcontrib>Guo, Ruichen</creatorcontrib><title>The protective effects of paeonol against epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice via inhibition of the PI3K/Akt/NF-kB pathway</title><title>Chemico-biological interactions</title><addtitle>Chem Biol Interact</addtitle><description>Epirubicin is widely used for the treatment of various breast cancers; however, it has serious adverse side effects, such as hepatotoxicity, which require dose-adjustment or therapy substitution. Paeonol, an active component from Moutan Cortex, has a variety of biological activities, including preventing or reducing various toxicities induced by antineoplastics. Protection by paeonol against hepatotoxicity induced by epirubicin and the underlying mechanism of action were investigated in this study. Cytosolic enzymes in the serum and oxidative stress indices in the liver were determined. The protective effects were determined using the MTT assay in vitro or by evaluating the expression of apoptotic factors and crucial proteins in the PI3K/Akt/NF-kB pathway using western blot analysis. It is concluded that paeonol alleviates epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice by inhibiting the PI3K/Akt/NF-kB pathway.
•Epirubicin is widely used to treat breast cancer, but limited for its hepatotoxicity.•Paeonol could alleviate epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice.•The mechanism relies on inhibiting the PI3K/Akt/NF-kB pathway.</description><subject>Acetophenones - pharmacology</subject><subject>Animals</subject><subject>Breast cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemical and Drug Induced Liver Injury - complications</subject><subject>Chemical and Drug Induced Liver Injury - drug therapy</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - prevention & control</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Drugs, Chinese Herbal - chemistry</subject><subject>Epirubicin</subject><subject>Epirubicin - adverse effects</subject><subject>Female</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>Hepatocytes - pathology</subject><subject>Hepatotoxicity</subject><subject>Mammary Neoplasms, Experimental - complications</subject><subject>Mammary Neoplasms, Experimental - drug therapy</subject><subject>Mice</subject><subject>NF-kappa B - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>Paeonia - chemistry</subject><subject>Paeonol</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>PI3K/Akt/NF-kB</subject><subject>Protective Agents - pharmacology</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Structure-Activity Relationship</subject><issn>0009-2797</issn><issn>1872-7786</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQxi0EokvhAbggH7kk63GcPytOpaJQUbUclrPlOJPubDdxsJ2l-xp9YrzawpGT7fE33-ibH2PvQeQgoFpuc9tSLgWUOUAuZPmCLaCpZVbXTfWSLYQQq0zWq_qMvQlhm55CKvGancmqUpWSsGBP6w3yybuINtIeOfZ9ugXuej4ZdKPbcXNvaAyR40R-bsnSmNHYzRY7vsHJRBfdY6rGA6eRqzVkcR6c5y0aT-M9H8gi35NJvxtqKZIbj-4xzf1xXXxfXjzE5e1V9vA5DYyb3-bwlr3qzS7gu-fznP28-rK-_Jbd3H29vry4yawqZcysAAu2aIsKlW1LKKq66VY9YlGrTpSqESCKtltho3psyq5PeaFVZWMMqBq74px9PPmm-L9mDFEPFCzudmZENwcNjZIlQFUXSQonqfUuBI-9njwNxh80CH1Eobc6odBHFBpAJxSp58Oz_dwO2P3r-Lv7JPh0EmAKuSf0OljCMe2VfGKgO0f_sf8DK8Calw</recordid><startdate>20160125</startdate><enddate>20160125</enddate><creator>Wu, Jing</creator><creator>Xue, Xia</creator><creator>Zhang, Bin</creator><creator>Jiang, Wen</creator><creator>Cao, Hongmei</creator><creator>Wang, Rongmei</creator><creator>Sun, Deqing</creator><creator>Guo, Ruichen</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20160125</creationdate><title>The protective effects of paeonol against epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice via inhibition of the PI3K/Akt/NF-kB pathway</title><author>Wu, Jing ; Xue, Xia ; Zhang, Bin ; Jiang, Wen ; Cao, Hongmei ; Wang, Rongmei ; Sun, Deqing ; Guo, Ruichen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-c01c1c3b36e4cb513678d9fee374d05480103bd9e84fe85df4211b458aa147ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acetophenones - pharmacology</topic><topic>Animals</topic><topic>Breast cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemical and Drug Induced Liver Injury - complications</topic><topic>Chemical and Drug Induced Liver Injury - drug therapy</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - prevention & control</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Drugs, Chinese Herbal - chemistry</topic><topic>Epirubicin</topic><topic>Epirubicin - adverse effects</topic><topic>Female</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>Hepatocytes - pathology</topic><topic>Hepatotoxicity</topic><topic>Mammary Neoplasms, Experimental - complications</topic><topic>Mammary Neoplasms, Experimental - drug therapy</topic><topic>Mice</topic><topic>NF-kappa B - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Paeonia - chemistry</topic><topic>Paeonol</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>PI3K/Akt/NF-kB</topic><topic>Protective Agents - pharmacology</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Jing</creatorcontrib><creatorcontrib>Xue, Xia</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Jiang, Wen</creatorcontrib><creatorcontrib>Cao, Hongmei</creatorcontrib><creatorcontrib>Wang, Rongmei</creatorcontrib><creatorcontrib>Sun, Deqing</creatorcontrib><creatorcontrib>Guo, Ruichen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Chemico-biological interactions</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Jing</au><au>Xue, Xia</au><au>Zhang, Bin</au><au>Jiang, Wen</au><au>Cao, Hongmei</au><au>Wang, Rongmei</au><au>Sun, Deqing</au><au>Guo, Ruichen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The protective effects of paeonol against epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice via inhibition of the PI3K/Akt/NF-kB pathway</atitle><jtitle>Chemico-biological interactions</jtitle><addtitle>Chem Biol Interact</addtitle><date>2016-01-25</date><risdate>2016</risdate><volume>244</volume><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>0009-2797</issn><eissn>1872-7786</eissn><abstract>Epirubicin is widely used for the treatment of various breast cancers; however, it has serious adverse side effects, such as hepatotoxicity, which require dose-adjustment or therapy substitution. Paeonol, an active component from Moutan Cortex, has a variety of biological activities, including preventing or reducing various toxicities induced by antineoplastics. Protection by paeonol against hepatotoxicity induced by epirubicin and the underlying mechanism of action were investigated in this study. Cytosolic enzymes in the serum and oxidative stress indices in the liver were determined. The protective effects were determined using the MTT assay in vitro or by evaluating the expression of apoptotic factors and crucial proteins in the PI3K/Akt/NF-kB pathway using western blot analysis. It is concluded that paeonol alleviates epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice by inhibiting the PI3K/Akt/NF-kB pathway.
•Epirubicin is widely used to treat breast cancer, but limited for its hepatotoxicity.•Paeonol could alleviate epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice.•The mechanism relies on inhibiting the PI3K/Akt/NF-kB pathway.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>26646421</pmid><doi>10.1016/j.cbi.2015.11.025</doi><tpages>8</tpages></addata></record> |
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| subjects | Acetophenones - pharmacology Animals Breast cancer Cell Line, Tumor Cell Proliferation - drug effects Chemical and Drug Induced Liver Injury - complications Chemical and Drug Induced Liver Injury - drug therapy Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - prevention & control Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Drugs, Chinese Herbal - chemistry Epirubicin Epirubicin - adverse effects Female Hepatocytes - drug effects Hepatocytes - metabolism Hepatocytes - pathology Hepatotoxicity Mammary Neoplasms, Experimental - complications Mammary Neoplasms, Experimental - drug therapy Mice NF-kappa B - metabolism Oxidative Stress - drug effects Paeonia - chemistry Paeonol Phosphatidylinositol 3-Kinases - metabolism PI3K/Akt/NF-kB Protective Agents - pharmacology Proto-Oncogene Proteins c-akt - metabolism Signal Transduction - drug effects Structure-Activity Relationship |
| title | The protective effects of paeonol against epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice via inhibition of the PI3K/Akt/NF-kB pathway |
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