Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27.
<h4>Background</h4>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 natura...
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oai:doaj.org-article:97ec74df58f24b0f91c10728b83b956b2021-11-18T07:35:25ZFlavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27.1932-620310.1371/journal.pone.0025302https://doaj.org/article/97ec74df58f24b0f91c10728b83b956b2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22065986/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>Our in vitro 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.<h4>Conclusions/significance</h4>These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induced cardiac toxicity.Yohann BernardNigel RibeiroFrédéric ThuaudGülen TürkeriRonan DirrMounia BoulberdaaCanan G NebigilLaurent DésaubryPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e25302 (2011) |
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Medicine R Science Q Yohann Bernard Nigel Ribeiro Frédéric Thuaud Gülen Türkeri Ronan Dirr Mounia Boulberdaa Canan G Nebigil Laurent Désaubry Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27. |
| description |
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>Our in vitro 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.<h4>Conclusions/significance</h4>These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induced cardiac toxicity. |
| format |
article |
| author |
Yohann Bernard Nigel Ribeiro Frédéric Thuaud Gülen Türkeri Ronan Dirr Mounia Boulberdaa Canan G Nebigil Laurent Désaubry |
| author_facet |
Yohann Bernard Nigel Ribeiro Frédéric Thuaud Gülen Türkeri Ronan Dirr Mounia Boulberdaa Canan G Nebigil Laurent Désaubry |
| author_sort |
Yohann Bernard |
| title |
Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27. |
| title_short |
Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27. |
| title_full |
Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27. |
| title_fullStr |
Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27. |
| title_full_unstemmed |
Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27. |
| title_sort |
flavaglines alleviate doxorubicin cardiotoxicity: implication of hsp27. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/97ec74df58f24b0f91c10728b83b956b |
| work_keys_str_mv |
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| _version_ |
1718423237136744448 |