RESUMO
Hepatocellular carcinoma (HCC) has become one of most common malignancies and a leading cause of cancer mortality worldwide. Previous study has shown that 4-acetylantroquinonol B (4AAQB) isolated from Antrodia cinnamomea (or niu-chang-chih) was observed to inhibit HepG2 cell proliferation via affecting cell cycle. However, the in vivo effects and antimetastatic activity of 4AAQB have not yet been addressed. This study found that 4AAQB inhibited HepG2 and HuH-7 hepatoma cell growth in both in vitro and in vivo models and exhibited pronounced inhibitory effects on HuH-7 tumor growth in xenograft and orthotopic models. 4AAQB efficiently inhibited the phosphorylation of mTOR and its upstream kinases and the downstream effectors and decreased the production of VEGF and activity of Rho GTPases in HuH-7 cells. Furthermore, 4AAQB inhibited in vitro HuH-7 cell migration and in vivo pulmonary metastasis. The results suggested that 4AAQB is a potential candidate for HCC therapy.
Assuntos
4-Butirolactona/análogos & derivados , Antineoplásicos/administração & dosagem , Antrodia/química , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Cicloexanonas/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , 4-Butirolactona/administração & dosagem , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Movimento Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Ossos do Metatarso , Camundongos Nus , Camundongos SCID , Fosforilação/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
[(125)I]RTI-55-membrane binding assay-guided fractionation and separation of a water-soluble extract of the roots of Polygala tenuifolia gave five new oligosaccharide derivatives, polygalatenosides A-E (1-5). The structures of these new oligosaccharides were established on the basis of spectroscopic evidence. Polygalatenosides A and B (1 and 2) showed significant inhibitory activity, with IC(50) values of 30.0 and 6.04 microM, respectively, in this membrane binding assay and acted as norepinephrine reuptake inhibitors through blocking norepinephrine transport.
