RESUMO
Berbamine, a natural compound from the plant Berberis amurensis, is a traditional Chinese medicine mainly used in stimulating normal hematopoiesis in clinic. Our previous studies demonstrated that berbamine has anti-leukemia activity. In this study, we investigated the anticancer activity of berbamine against human hepatocellular carcinoma (HCC) HepG2 cells in vitro and in vivo. Berbamine treatment decreased the cell growth in a dose-dependent manner with an IC(50) value of 34.5 +/- 0.5 microM. Flow cytometric analysis of apoptosis using Annexin V/propidium iodide staining showed that the percentage of apoptotic cells was increased in a time-dependent manner. Berbamine treatment increased the expression level of Fas and P53, caused depolarization of mitochondrial membrane and decrease of membrane potential, and activated caspase-3, -8, and -9 in HepG2 cells. Berbamine-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk. HepG2 human HCC xenograft mice treated with berbamine showed a significant reduction in tumor growth rates compared to saline-treated mice. These studies suggest that berbamine exerts anticancer effects on human HCC HepG2 cells in vivo and in vitro, the induction of p53 and the activity of the Fas apoptotic system may participate in the anticancer activity of berbamine in HepG2 cells.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Benzilisoquinolinas/química , Benzilisoquinolinas/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacocinética , Apoptose/efeitos dos fármacos , Benzilisoquinolinas/farmacocinética , Berberina/química , Bisbenzimidazol/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Plantas Medicinais/química , Fatores de Tempo , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor fas/metabolismoRESUMO
OBJECTIVE: To study the effects of brucea javanica oil on the expression of vascular endothelial growth factor (VEGF) in A549 cell line. METHOD: A549 cells were incubated with different concentrations of brucea javanica oil (0.5, 1.25, 2.5, 5 g x L(-1) for 48 h respectively. VEGF level in supernatant was determined by VEGF ELISA kits and mRNA expression of VEGF was evaluated by RT-PCR. PMN in health volunteers was treated as control groups. RESULT: Supernatant VEGF protein and mRNA expression were significantly elevated in A549 cells compared with the mononuclear cells (120.73 vs 21.21, P < 0.05). Brucea javanica oil (2.5 g x L(-1)) could reduced supernatant VEGF protein in A549 cells (20.30 vs 120.73, P < 0.05), but had no effect on the expression of VEGF mRNA (1.0230 vs 0.9573). It was found that brucea javanica oil (5 g x L(-1)) significantly reduced VEGF mRNA expression (0.4682 vs 0.9573, P < 0.05). CONCLUSION: Brucea javanica oil can depress the VEGF mRNA expression and secretion in A549 cells, which may be one of the mechanisms of its antitumor effect.