title: Liquiritigenin inhibits serum-induced HIF-1α and VEGF expression via the AKT/mTOR-p70S6K signalling pathway in HeLa cells.
abstract: Liquiritigenin (LQ) is a non-toxic dietary flavonoid with chemopreventive and anticancer properties. However, the mechanism of its antiangiogenesis remains unclear. Hypoxia-inducible factor-1α (HIF-1α) and its downstream target, vascular endothelial growth factor (VEGF), play a critical role in tumour angiogenesis and represent an attractive chemotherapeutic target. In this study, we investigated the effect of LQ on the molecular mechanism of angiogenesis. We found that LQ inhibited VEGF expression at both mRNA and protein levels. Liquiritigenin did not affect HIF-1α expression at the mRNA level, but it dramatically inhibited both serum- and mimicked hypoxic-induced HIF-1α protein accumulation in HeLa cells. Furthermore, we showed that LQ inhibited serum-induced expression of HIF-1α by reducing its stability and decreased the synthesis in a dose-dependent manner. Mechanistically, we demonstrated that LQ inhibited HIF-1α and VEGF expression involved in blocking the protein kinase B (PKB/Akt) signalling pathway, and the mechanisms correlated with dephosphorylation of the mammalian target of rapamycin (mTOR) and its effector ribosomal protein S6 kinase (p70S6K). In addition, LQ inhibited VEGF-induced formation of capillary-like structures in human umbilical vein endothelial cells (HUVEC). Taken together, our study provided valuable insights into the mechanism of antiangiogenic effect of LQ.
authors.affiliation: Department of Nutrition and Food Hygiene, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, P. R. China.
authors.forename: Si-Rou
authors.initials: SR
authors.lastname: Xie
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Chang-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Kang
authors.initials: K
authors.lastname: Luo
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Cai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D044950:Flavanones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019869:Phosphatidylinositol 3-Kinases; D012333:RNA, Messenger; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C497442:HIF1A protein, human; C467484:VEGFA protein, human; C546842:MTOR protein, human; C083152:liquiritigenin