title: Inhibition of endothelial cell functions by novel potential cancer chemopreventive agents.
abstract: Endothelial cells (EC) play a major role in tumor-induced neovascularization and bridge the gap between a microtumor and growth factors such as nutrients and oxygen supply required for expansion. Immortalized human microvascular endothelial cells (HMEC-1) were utilized to assess anti-endothelial effects of 10 novel potential cancer chemopreventive compounds from various sources that we have investigated previously in a human in vitro anti-angiogenic assay. These include the monoacylphloroglucinol isoaspidinol B, 1,2,5,7-tetrahydroxy-anthraquinone, peracetylated carnosic acid (PCA), isoxanthohumol, 2,2',4'-trimethoxychalcone, 3'-bromo-2,4-dimethoxychalcone as well as four synthetic derivatives of lunularic acid, a bibenzyl found in mosses [Int. J. Cancer Prev. 1 (2004) 47]. EC proliferation was inhibited with half-maximal inhibitory concentrations from 0.3 to 49.6muM, whereas EC migration was affected by most compounds at sub-micromolar concentrations. PCA and the bibenzyl derivative EC 1004 potently prevented differentiation of HMEC-1 into tubule-like structures. Overall, our data indicate that inhibition of endothelial cell function contributes to various extents to the chemopreventive or anti-angiogenic potential of these lead compounds.
authors.affiliation: Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bertl
authors.forename: Hans
authors.initials: H
authors.lastname: Becker
authors.forename: Theophil
authors.initials: T
authors.lastname: Eicher
authors.forename: Christian
authors.initials: C
authors.lastname: Herhaus
authors.forename: Govind
authors.initials: G
authors.lastname: Kapadia
authors.forename: Helmut
authors.initials: H
authors.lastname: Bartsch
authors.forename: Clarissa
authors.initials: C
authors.lastname: Gerhäuser
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents