title: Antiangiogenic and Anticancer Properties of Bifunctional Ruthenium(II)-p-Cymene Complexes: Influence of Pendant Perfluorous Chains.
abstract: Two bifunctional ruthenium(II)-p-cymene complexes with perfluorinated side chains, attached via pyridine ligands, have been evaluated in a series of in vitro and in vivo assays. Their effects on human endothelial (ECRF24 and HUVEC) cells, noncancerous human embryonic kidney (HEK-293) cells, and various human tumor cells were investigated. The complex with the shorter chain, 1, inhibits the proliferation of the tumor cell lines and ECRF24, whereas 2 selectively inhibits ECRF24 and HUVEC proliferation. Neither inhibits the migration of ECRF24 cells whereas both compounds inhibit sprout formation in HUVEC cells. Using three preclinical models, i.e., vasculature formation in the chorioallantoic membrane (CAM) of the chicken embryo, human A2780 ovarian carcinoma tumors xenografted on the CAM, and human LS174T colorectal adenocarcinoma tumors grown in athymic mice, the angiostatic and anticancer activities of these two complexes were studied. Overall, 1 inhibited tumor growth predominantly through an anticancer effect whereas 2 inhibited tumor growth predominately via an antiangiogenic mechanism.
authors.affiliation: †Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.|‡Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Nowak-Sliwinska
authors.affiliation: ‡Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Clavel
authors.affiliation: ‡Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Păunescu
authors.affiliation: †Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.|‡Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland.
authors.forename: Marije T
authors.initials: MT
authors.lastname: te Winkel
authors.affiliation: †Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Arjan W
authors.initials: AW
authors.lastname: Griffioen
authors.affiliation: ‡Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000081007:Cymenes; D004354:Drug Screening Assays, Antitumor; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008958:Models, Molecular; D039821:Monoterpenes / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000081007:Cymenes; D039821:Monoterpenes; D009942:Organometallic Compounds; C007210:4-cymene; D012428:Ruthenium
keywords: CAM model; antiangiogenesis; bioorganometallic chemistry; colorectal adenocarcinoma; fluorine chemistry; ovarian carcinoma; ruthenium(II)−arene complexes