Anti-angiogenic effect of a Palladium(II)-Saccharinate Complex of Terpyridine in vitro and in vivo.
Anti-angiogenic activity of palladium (Pd)(II)-based complexes is unknown despite their quite powerful anticancer activity. This study was therefore carried out to evaluate both in vivo anti-angiogenic effect and in vitro cytotoxic activity of a Pd(II)-based complex. ([Pd(sac)(terpy)](sac)·4H2O(sac=saccharinate and terpy=2,2':6',2″-terpyridine)) on HUVEC cells. The anti-angiogenic activity of the complex was evaluated in vivo using the chick embryo chorioallantoic membrane (CAM) assay, tube formation assay and the cytotoxicity was screened using the MTT viability assays. The CAM treated with the complex (50μg/pellet) showed a strikingly high anti-angiogenic effect (score 1.1±0.2) compared to the positive controls cortisone, prednisone and (±)-thalidomide (e.g. (±)-thalidomide score 0.9±0.2) tested at the same concentration. Furthermore, the complex showed neither membrane toxicity nor irritation at the tested concentration. According to the MTT assays, the human umbilical vein endothelial cell (HUVEC) viability was inhibited in a dose-dependent manner at tested concentrations (1.56-100μM). Pd(II) complex also reduced the tube network at the lower dose than the compared with thalidomide. These results suggest that the Pd(II)-complex has strong anti-angiogenic activity, which adds an important feature to the previously-described anticancer activity of the complex.
Department of Histology and Embryology, Faculty of Veterinary Medicine, Istanbul University, 34320 Istanbul, Turkey. Electronic address: elifarmutak@gmail.com.
Elif I
EI
Ikitimur-Armutak
Department of Biology, Faculty of Science, Istanbul University, 34134 Istanbul, Turkey.
Ebru
E
Gurel-Gurevin
Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey.
H Tuba
HT
Kiyan
Department of Molecular Biology, Faculty of Science, Uludag University, 16059 Bursa, Turkey.
Seyma
S
Aydinlik
Department of Chemistry, Faculty of Arts and Sciences, Uludag University, 16059 Bursa, Turkey.
Veysel Turan
VT
Yilmaz
Department of Pharmacology, School of Medicine, Thessaly University, Larissa, Greece.
Konstantinos
K
Dimas
Department of Clinical Biochemistry, School of Medicine, Uludag University, 16059 Bursa, Turkey.
Engin
E
Ulukaya
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011725:Pyridines; D010165:Palladium
Anti-angiogenic; Chick chorioallantoic membrane (CAM) assay; MTT assay; Palladium(II)-Saccharinate Complex of Terpyridine; Tube formation assay