title: Acacetin inhibits VEGF expression, tumor angiogenesis and growth through AKT/HIF-1α pathway.
abstract: Acacetin (5,7-dihydroxy-4'-methoxyflavone) is a flavone compound, some of which have anti-cancerous effects. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and tumor growth. In this study, we found that acacetin decreased the steady level of VEGF mRNA level and inhibited VEGF transcriptional activation. To further determine the potential mechanism of acacetin in inhibiting VEGF expression, we showed that acacetin inhibited HIF-1α expression and AKT activation. Over-expression of HIF-1α or AKT restored acacetin-decreasing VEGF transcriptional activation, indicating that AKT and HIF-1 are the essential downstream targets of acacetin for inhibiting VEGF expression in the cells. Moreover, acacetin significantly inhibited ovarian cancer cell-induced angiogenesis and tumor growth in vivo through inhibiting HIF-1α and VEGF expression. Acacetin did not change HIF-1α mRNA level, but inhibited HIF-1α protein level through increasing its degradation and decreasing its stability. These results indicate that acacetin may be a useful natural compound for ovarian cancer prevention and treatment.
authors: Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors: Ling-Zhi
authors: LZ
authors: Liu
authors: Yi
authors: Y
authors: Jing
authors: Lisa L
authors: LL
authors: Jiang
authors: Xiu-E
authors: XE
authors: Jiang
authors: Yue
authors: Y
authors: Jiang
authors: Yongyut
authors: Y
authors: Rojanasakul
authors: Bing-Hua
authors: BH
authors: Jiang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D005260:Female; D047309:Flavones / Q000627:therapeutic use*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015533:Transcriptional Activation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D047309:Flavones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt; C023717:acacetin