Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells.
Biochem Biophys Res Commun
; 409(3): 489-93, 2011 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-21600879
ABSTRACT
We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pironas
/
Carcinoma
/
Neoplasias do Colo do Útero
/
Espécies Reativas de Oxigênio
/
Proteínas Serina-Treonina Quinases
/
Proteínas de Ciclo Celular
/
Proteínas Supressoras de Tumor
/
Proteínas de Ligação a DNA
/
Compostos de Epóxi
/
Antibióticos Antineoplásicos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article