RESUMO
Torilin is a sesquiterpene compound purified from fruits of Torilis japonica (Umbelliferae). In this study, we demonstrated the anti-angiogenic activity of torilin using in vivo and in vitro assay systems. Torilin decreased both neovascularization of chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. Torilin also reduced the proliferation and tube formation of human umbilical vein endothelial cells. In addition, the concentrated conditioned media obtained from torilin-treated HepG2 human hepatoblastoma cells blocked the angiogenic activation of torilin-untreated concentrated conditioned media, indicating that torilin may have an inhibitory effect on tumor-induced angiogenesis. To determine what molecules were involved in the anti-angiogenic activity, we examined the expression of hypoxia-inducible angiogenic factors in torilin-treated HepG2 cells. Torilin significantly down-regulated the expression of hypoxia-inducible vascular endothelial growth factor and insulin-like growth factor-II. Taken together, our data suggest that torilin may be a strong angiogenic inhibitor with the ability to decrease tube formation of vascular endothelial cells and to reduce expression of angiogenic factors of tumor cells.
Assuntos
Inibidores da Angiogênese/farmacologia , Neovascularização Patológica , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Animais , Northern Blotting , Divisão Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Embrião de Galinha , Colágeno/metabolismo , Colágeno/farmacologia , Meios de Cultivo Condicionados/farmacologia , Regulação para Baixo , Combinação de Medicamentos , Fatores de Crescimento Endotelial/metabolismo , Endotélio Vascular/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Hipóxia , Fator de Crescimento Insulin-Like II/metabolismo , Laminina/metabolismo , Linfocinas/metabolismo , Camundongos , Proteoglicanas/metabolismo , Sesquiterpenos/química , Sesquiterpenos de Guaiano , Fatores de Tempo , Células Tumorais Cultivadas , Veias Umbilicais/metabolismo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Scutellaria baicalensis (SB) has antibacterial and antiviral activities. Nitric oxide (NO) as a potent macrophage-derived effector molecule against a variety of bacteria, viruses and tumors has received increasing attention. The objective of this study was to determine the effect of SB on the production of NO. Stimulation of mouse peritoneal macrophages with SB after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in the increased NO production. SB had no effect on NO production by itself. When SB was used in combination with rIFN-gamma, there was a marked cooperative induction of NO production in a dose-dependent manner. The optimal effect of SB on NO production was shown 6 h after treatment with rIFN-gamma. NO production by SB was inhibited by N(G)-monomethyl-L-arginine. The increased production of NO from rIFN-(gamma) plus SB-stimulated cells was decreased by the treatment of protein kinase C inhibitor such as staurosporin. In addition, synergy between rIFN-gamma and SB was mainly dependent on SB-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the preparations of SB were endotoxin free. These results suggest that the capacity of SB to increase NO production from rIFN-gamma-primed mouse peritoneal macrophages is the result of SB-induced TNF-gamma secretion.