title: Enhancement of Antiangiogenic Efficacy of Iron(II) Complex by Selenium Substitution.
abstract: Antiangiogenesis therapy is a proven strategy for the treatment of cancers. Herein, we demonstrate that iron(II) complexes containing 1,10-phenanthroline(phen) derivatives were capable of suppressing angiogenesis in vitro in a dose-dependent manner. Interestingly, the introduction of selenium into an iron(II) complex ((Fe(phenSe)3(ClO4)2(phenSe=2-selenoimidazole[4,5-f]1,10-phenanthroline)) could enhance its antiangiogenic efficacy. Mechanistic studies demonstrated that the complex potently induced endothelial cell apoptosis as evidenced by activation of caspases and PARP cleavage. The iron(II) complex activated p53-mediated mitochondrial dysfunction as can be seen by the upregulation in the expression of p53 and proapoptotic Bcl-2 family proteins, and downregulation in the expression of Bcl-2 family proteins. Additionally, the complex inhibited VEGF expression and gave rise to dephosphorylated AKT, which suppressed the transmission of the mitogenic signaling pathway. Taken together, this study could provide a strategy for the rational design of high-efficacy antivascular agents.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Haoqiang
authors.initials: H
authors.lastname: Lai
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Feng
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou, 510632, China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D012643:Selenium / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D020533:Angiogenesis Inhibitors; D005296:Ferrous Compounds; D012643:Selenium
keywords: VEGF; angiogenesis; apoptosis; iron; selenium