Flavaglines Alleviate Doxorubicin Cardiotoxicity: Implication of Hsp27
Identifieur interne : 001585 ( Main/Exploration ); précédent : 001584; suivant : 001586Flavaglines Alleviate Doxorubicin Cardiotoxicity: Implication of Hsp27
Auteurs : Yohann Bernard [France] ; Nigel Ribeiro [France] ; Frédéric Thuaud [France] ; Gülen Türkeri [France] ; Ronan Dirr [France] ; Mounia Boulberdaa [France] ; Canan G. Nebigil [France] ; Laurent Désaubry [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
Despite its effectiveness in the treatment of various cancers, the use of doxorubicin is limited by a potentially fatal cardiomyopathy. Prevention of this cardiotoxicity remains a critical issue in clinical oncology. We hypothesized that flavaglines, a family of natural compounds that display potent neuroprotective effects, may also alleviate doxorubicin-induced cardiotoxicity.
Our
These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induced cardiac toxicity.
Url:
DOI: 10.1371/journal.pone.0025302
PubMed: 22065986
PubMed Central: 3204970
Affiliations:
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Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, FRE 3211, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, FRE 3211, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Ribeiro, Nigel" sort="Ribeiro, Nigel" uniqKey="Ribeiro N" first="Nigel" last="Ribeiro">Nigel Ribeiro</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Thuaud, Frederic" sort="Thuaud, Frederic" uniqKey="Thuaud F" first="Frédéric" last="Thuaud">Frédéric Thuaud</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Turkeri, Gulen" sort="Turkeri, Gulen" uniqKey="Turkeri G" first="Gülen" last="Türkeri">Gülen Türkeri</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, FRE 3211, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, FRE 3211, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Dirr, Ronan" sort="Dirr, Ronan" uniqKey="Dirr R" first="Ronan" last="Dirr">Ronan Dirr</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Boulberdaa, Mounia" sort="Boulberdaa, Mounia" uniqKey="Boulberdaa M" first="Mounia" last="Boulberdaa">Mounia Boulberdaa</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, FRE 3211, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, FRE 3211, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Nebigil, Canan G" sort="Nebigil, Canan G" uniqKey="Nebigil C" first="Canan G." last="Nebigil">Canan G. Nebigil</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, FRE 3211, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, FRE 3211, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author><author><name sortKey="Desaubry, Laurent" sort="Desaubry, Laurent" uniqKey="Desaubry L" first="Laurent" last="Désaubry">Laurent Désaubry</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Therapeutic Innovation Laboratory, UMR7200, CNRS/Université de Strasbourg, Illkirch</wicri:regionArea><wicri:noRegion>Illkirch</wicri:noRegion><orgName type="university">Université de Strasbourg</orgName><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Despite its effectiveness in the treatment of various cancers, the use of doxorubicin is limited by a potentially fatal cardiomyopathy. Prevention of this cardiotoxicity remains a critical issue in clinical oncology. We hypothesized that flavaglines, a family of natural compounds that display potent neuroprotective effects, may also alleviate doxorubicin-induced cardiotoxicity.</p></sec><sec><title>Methodology/Principal Findings</title><p>Our <italic>in vitro</italic> data established that a pretreatment with flavaglines significantly increased viability of doxorubicin-injured H9c2 cardiomyocytes as demonstrated by annexin V, TUNEL and active caspase-3 assays. We demonstrated also that phosphorylation of the small heat shock protein Hsp27 is involved in the mechanism by which flavaglines display their cardioprotective effect. Furthermore, knocking-down Hsp27 in H9c2 cardiomyocytes completely reversed this cardioprotection. Administration of our lead compound (FL3) to mice attenuated cardiomyocyte apoptosis and cardiac fibrosis, as reflected by a 50% decrease of mortality.</p></sec><sec><title>Conclusions/Significance</title><p>These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induced cardiac toxicity.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cortes Funes, H" uniqKey="Cortes Funes H">H Cortes-Funes</name></author><author><name sortKey="Coronado, C" uniqKey="Coronado C">C Coronado</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Minotti, G" uniqKey="Minotti G">G Minotti</name></author><author><name sortKey="Menna, P" uniqKey="Menna P">P Menna</name></author><author><name sortKey="Salvatorelli, E" uniqKey="Salvatorelli E">E Salvatorelli</name></author><author><name sortKey="Cairo, G" uniqKey="Cairo G">G Cairo</name></author><author><name sortKey="Gianni, L" 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Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Griffin, Mo" uniqKey="Griffin M">MO Griffin</name></author><author><name sortKey="Fricovsky, E" uniqKey="Fricovsky E">E Fricovsky</name></author><author><name sortKey="Ceballos, G" uniqKey="Ceballos G">G Ceballos</name></author><author><name sortKey="Villarreal, F" uniqKey="Villarreal F">F Villarreal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, Hc" uniqKey="Lai H">HC Lai</name></author><author><name sortKey="Yeh, Yc" uniqKey="Yeh Y">YC Yeh</name></author><author><name sortKey="Ting, Ct" uniqKey="Ting C">CT Ting</name></author><author><name sortKey="Lee, Wl" uniqKey="Lee W">WL Lee</name></author><author><name sortKey="Lee, Hw" uniqKey="Lee H">HW Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mai, A" uniqKey="Mai A">A Mai</name></author><author><name sortKey="Rotili, D" uniqKey="Rotili D">D Rotili</name></author><author><name sortKey="Valente, S" uniqKey="Valente S">S Valente</name></author><author><name sortKey="Kazantsev, Ag" uniqKey="Kazantsev A">AG Kazantsev</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li></country><region><li>Alsace (région administrative)</li><li>Grand Est</li></region><settlement><li>Strasbourg</li></settlement><orgName><li>Université de Strasbourg</li></orgName></list><tree><country name="France"><region name="Grand Est"><name sortKey="Bernard, Yohann" sort="Bernard, Yohann" uniqKey="Bernard Y" first="Yohann" last="Bernard">Yohann Bernard</name></region><name sortKey="Bernard, Yohann" sort="Bernard, Yohann" uniqKey="Bernard Y" first="Yohann" last="Bernard">Yohann Bernard</name><name sortKey="Boulberdaa, Mounia" sort="Boulberdaa, Mounia" uniqKey="Boulberdaa M" first="Mounia" last="Boulberdaa">Mounia Boulberdaa</name><name sortKey="Desaubry, Laurent" sort="Desaubry, Laurent" uniqKey="Desaubry L" first="Laurent" last="Désaubry">Laurent Désaubry</name><name sortKey="Dirr, Ronan" sort="Dirr, Ronan" uniqKey="Dirr R" first="Ronan" last="Dirr">Ronan Dirr</name><name sortKey="Nebigil, Canan G" sort="Nebigil, Canan G" uniqKey="Nebigil C" first="Canan G." last="Nebigil">Canan G. Nebigil</name><name sortKey="Ribeiro, Nigel" sort="Ribeiro, Nigel" uniqKey="Ribeiro N" first="Nigel" last="Ribeiro">Nigel Ribeiro</name><name sortKey="Thuaud, Frederic" sort="Thuaud, Frederic" uniqKey="Thuaud F" first="Frédéric" last="Thuaud">Frédéric Thuaud</name><name sortKey="Turkeri, Gulen" sort="Turkeri, Gulen" uniqKey="Turkeri G" first="Gülen" last="Türkeri">Gülen Türkeri</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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