title: Stabilization of VEGF G-quadruplex and inhibition of angiogenesis by quindoline derivatives.
abstract: BACKGROUND
  Angiogenesis is thought to be important in tumorigenesis and tumor progress. Vascular endothelial growth factor (VEGF) is a pluripotent cytokine and angiogenic growth factor that plays crucial roles in embryonic development and tumor progression. In many types of cancer, VEGF is overexpressed and is generally associated with tumor progression and survival rate. The polypurine/polypyrimidine sequence located upstream of the promoter region in the human VEGF gene can form specific parallel G-quadruplex structures, raising the possibility for transcriptional control of VEGF through G-quadruplex ligands.
  
  
  METHODS
  PCR stop assay, circular dichroism (CD) spectra, RNA extraction and RT-PCR, enzyme-linked immunosorbent assay (ELISA), luciferase Assays, cell scrape test, xCELLigence real-time cell analysis (RTCA), and chick embryo chorioallantoic membrane (CAM) assay.
  
  
  CONCLUSIONS
  We found that quindoline derivatives can interact with the G-rich DNA sequences of the VEGF promoter to stabilize this G-quadruplex and suppress the transcription and expression of the VEGF protein. We also demonstrated that these derivatives exhibit potential anti-angiogenic activity in chick embryos and antitumor activity, including the inhibition of cell proliferation and migration.
  
  
  CONCLUSIONS
  Our new findings have significances not only for understanding the mechanism of the G-quadruplex ligands mediating the VEGF transcription inhibition, but also for exploring a new anti-tumor strategy to blocking the transcription of VEGF to inhibit the angiogenesis in cancer cells.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou University City, Guangzhou 510006, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou University City, Guangzhou 510006, PR China.
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Zan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou University City, Guangzhou 510006, PR China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, PR China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou University City, Guangzhou 510006, PR China. Electronic address: outianm@mail.sysu.edu.cn.
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou University City, Guangzhou 510006, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou University City, Guangzhou 510006, PR China.
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou University City, Guangzhou 510006, PR China.
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D002942:Circular Dichroism; D018899:CpG Islands; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D011804:Quinolines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000470:Alkaloids; D007211:Indoles; D008024:Ligands; D011804:Quinolines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C016712:quindoline
keywords: Angiogenesis; Anti-tumor; G-quadruplex; Quindoline derivative; VEGF