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.