AD-1, a novel ginsenoside derivative, shows anti-lung cancer activity via activation of p38 MAPK pathway and generation of reactive oxygen species.
Biochim Biophys Acta
; 1830(8): 4148-59, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23583729
ABSTRACT
BACKGROUND:
Ginseng is a traditional Chinese herb that has been used for thousands of years. In the present study, effects and mechanisms of AD-1 were evaluated for its development as a novel anti-lung cancer drug.METHODS:
The cytotoxic activity was evaluated by MTT assay. Flow cytometry was employed to detect cell cycle, apoptosis and ROS. Western blot and immunohistochemistry were used to analyze signaling pathways. Lung cancer xenograft models were established by subcutaneous implantation of A549 or H292 cells into nude mice.RESULTS:
AD-1 concentration-dependently reduces lung cancer cell viability without affecting normal human lung epithelial cell viability. In A549 and H292 lung cancer cells, AD-1 induces G0/G1 cell cycle arrest, apoptosis and ROS production. The apoptosis can be attenuated by a ROS scavenger - N-acetylcysteine (NAC). In addition, AD-1 up-regulates the expression of p38 and ERK phosphorylation. Addition of a p38 inhibitor SB203580, suppresses the AD-1-induced decrease in cell viability. Furthermore, genetic silencing of p38 attenuates the expression of p38 and decreases the AD-1-induced apoptosis. Treatment with NAC reduces AD-1-induced p38 phosphorylation, which indicates that ROS generation is involved in the AD-1-induced p38 activation. In mice, oral administration of AD-1 (10-40mg/kg) dose-dependently inhibited the growth of xenograft tumors without affecting body weight and decreases the expression of VEGF, MMP-9 and CD34 in tumor tissue. TUNEL staining confirms that the tumors from AD-1 treated mice exhibit a markedly higher apoptotic index. CONCLUSIONS AND GENERALSIGNIFICANCE:
These data support development of AD-1 as a potential agent for lung cancer therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
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Sistema de Sinalização das MAP Quinases
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Ginsenosídeos
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Proteínas Quinases p38 Ativadas por Mitógeno
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Neoplasias Pulmonares
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China