A novel compound modified from tanshinone inhibits tumor growth in vivo via activation of the intrinsic apoptotic pathway.
Cancer Lett
; 297(1): 18-30, 2010 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-20494511
ABSTRACT
A novel compound, acetyltanshinone IIA (ATA) was obtained from chemical modifications of tanshinone TIIA (TIIA) isolated from a medicinal plant, Salvia miltiorrhiza. ATA exhibited increased water solubility and stronger apoptotic activity on multiple cancer cell lines than TIIA. ATA displayed a higher growth inhibition ability on breast cancer especially HER2 positive cells than normal cells and it inhibited xenografted tumor growth in mice. Mechanistic studies showed that ATA could induce significant reactive oxygen species (ROS) generation, Bax translocation to mitochondria, resulting in mitochondria damage, cytochrome c release, caspase-3 activation and apoptotic cell death. ATA-mediated ROS production and its downstream apoptotic events could be blocked by an antioxidant agent, propyl gallate, indicating the prominent role of ROS in ATA-induced apoptosis. Overexpression of Bcl-2 protein reduced ATA-induced cell death. In conclusion, ATA is a novel anticancer agent with potent in vitro and in vivo anticancer ability. ROS-mediated Bax activation should be the mechanism by which ATA induces apoptosis and inhibits tumor growth.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenantrenos
/
Apoptosis
/
Carga Tumoral
/
Proliferación Celular
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Neoplasias
/
Antineoplásicos Fitogénicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cancer Lett
Año:
2010
Tipo del documento:
Article
País de afiliación:
Hong Kong