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Ain Hypoxiainducible factor 1 (HIF1), a heterodimeric transcription factor that mediates the adaptation of tumor cells and tissues to the hypoxic microenvironment, has attracted considerable interest as a potential therapeutic target.Kamebakaurin is a diterpenoid compound isolated from lsodonexcia (Maxin.) Hara, which has been used for antiinflammatory activities.But its antitumor activity has not been reported.Kamebakaurin showed the potent inhibitory activity against HIF1 activation by CoCl2 induced hypoxia in various human cancer cell lines.This compound significantly decreased the hypoxiainduced accumulation of HIF1 α protein, whereas it did not affect the expressions of topoisomeraseⅠ (TopoⅠ).Further analysis revealed that kamebakaurin inhibited HIF1αprotein synthesis, without affecting the expression level of HIF1 ot mRNA or degradation of HIF1 α protein.Furthermore, kamebakaurin prevented hypoxiainduced expression of HIF1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO).However, kamebakaurin caused cell growth inhibition via cell cycle arrest at G1 in tumor cells.In vivo studies, we further confirmed the inhibitory effect of kamebakaurin on the expression of HIF1α proteins, leading to a decrease growth of HCT116 cells in a xenograft tumor model.These results show that kamebakaurin is an effective inhibitor of HIF1 and provide new perspectives into its anticancer activity.