title: Down-regulation of the human VEGF gene expression by perylene monoimide derivatives.
abstract: The proximal promoter region of the human vascular endothelial growth factor (VEGF) gene contains a guanine-rich strand that can act as a transcriptional silencer by forming an intramolecular G-quadruplex. In this study, we compared two perylene monoimide derivatives, PM1 and PM2, with the well-studied perylene diimide derivative, PIPER, and the well-studied porphyrin derivative, TmPyP(4), with regard to G-quadruplex formation, G-quadruplex binding selectivity, and human VEGF gene silencing in A549 lung cancer cells. The results show that these perylene derivatives can preferentially induce intramolecular G-quadruplex formation from a duplex containing the VEGF G-quadruplex motif in vitro. Incubating A549 lung cancer cells with these perylene derivatives, especially PM2, led to the reduction of both VEGF mRNA and VEGF protein. This study might provide the foundation for the rational design and development of new perylene derivatives as effective anti-angiogenesis agents for cancer therapy.
authors: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors: Thanachai
authors: T
authors: Taka
authors: Khajohn
authors: K
authors: Joonlasak
authors: Liming
authors: L
authors: Huang
authors: T
authors: T
authors: Randall Lee
authors: Suk-Wah Tam
authors: SW
authors: Chang
authors: Wirote
authors: W
authors: Tuntiwechapikul
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015195:Drug Design; D054856:G-Quadruplexes; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007094:Imides / Q000737:chemistry* / Q000494:pharmacology; D008954:Models, Biological; D008956:Models, Chemical; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007094:Imides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C521332:perylenediimide; D010569:Perylene