Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro.
BMC Complement Altern Med
; 12: 138, 2012 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-22920231
ABSTRACT
BACKGROUND:
Doxorubicin (DOX) is an effective antineoplastic drug; however, clinical use of DOX is limited by its dose-dependent cardiotoxicity. It is well known that reactive oxygen species (ROS) play a vital role in the pathological process of DOX-induced cardiotoxicity. For this study, we evaluated the protective effects of guggulsterone (GS), a steroid obtained from myrrh, to determine its preliminary mechanisms in defending against DOX-induced cytotoxicity in H9C2 cells.METHODS:
In this study, we used a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release measurements, and Hoechst 33258 staining to evaluate the protective effect of GS against DOX-induced cytotoxicity in H9C2 cells. In addition, we observed the immunofluorescence of intracellular ROS and measured lipid peroxidation, caspase-3 activity, and apoptosis-related proteins by using Western blotting.RESULTS:
The MTT assay and LDH release showed that treatment using GS (1-30 µM) did not cause cytotoxicity. Furthermore, GS inhibited DOX (1 µM)-induced cytotoxicity in a concentration-dependent manner. Hoechst 33258 staining showed that GS significantly reduced DOX-induced apoptosis and cell death. Using GS at a dose of 10-30 µM significantly reduced intracellular ROS and the formation of MDA in the supernatant of DOX-treated H9C2 cells and suppressed caspase-3 activity to reference levels. In immunoblot analysis, pretreatment using GS significantly reversed DOX-induced decrease of PARP, caspase-3 and bcl-2, and increase of bax, cytochrome C release, cleaved-PARP and cleaved-caspase-3. In addition, the properties of DOX-induced cancer cell (DLD-1 cells) death did not interfere when combined GS and DOX.CONCLUSION:
These data provide considerable evidence that GS could serve as a novel cardioprotective agent against DOX-induced cardiotoxicity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pregnenodionas
/
Terpenos
/
Doxorrubicina
/
Substâncias Protetoras
/
Miócitos Cardíacos
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article