Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27.
PLoS One
; 6(10): e25302, 2011.
Article
em En
| MEDLINE
| ID: mdl-22065986
ABSTRACT
BACKGROUND:
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. METHODOLOGY/PRINCIPALFINDINGS:
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. CONCLUSIONS/SIGNIFICANCE:
These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induced cardiac toxicity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzofuranos
/
Doxorrubicina
/
Miócitos Cardíacos
/
Proteínas de Choque Térmico HSP27
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
França