Apoptosis-inducing Effect of a Palladium(II) Complex-[PdCl(terpy)](sac)•2H2O] on Ehrlich Ascites Carcinoma (EAC) in Mice

Abstract

Background/Aim: New compounds for cancer treatment are needed due to persistenly unsatisfactory management of cancer. [PdCl(terpy)](sac)center dot 2H2O] (sac= saccharinate, and terpy= 2,2':6',2 ''- terpyridine) is a compound synthesized for this purpose. We investigated its anti-proliferative and pro-apoptotic effects on Ehrlich Ascites Carcinoma (EAC) in vivo. Materials and Methods: 42 Balb-c female mice were subcutaneously (s.c.) injected with EAC cells (1st day) and then randomly divided into 5 groups: control (0.9% NaCl), complex (2 mg/kg), complex (3 mg/kg) cisplatin (4 mg/kg) and paclitaxel (12.5 mg/kg). On the 5th and 12th day animals were drug administrated. At 14th day, animals were sacrificed. Expression of cell death and/or cell cycle-related markers (Bcl-2, Bax, active caspase-3, p53, PCNA) and apoptosis were investigated immunohisto-chemically. Survival-related markers (Akt, GSK-3 beta, IGF-1R, IR, IRS-1, p70S6K, PRAS40) were evaluated by luminex analysis. Results: Expression of p53, PCNA, Bcl-2 was found decreased (p< 0.001) and that of active caspase-3, Bax, and apoptotic cells was found increased (p< 0.001) in all groups. The survivalrelated markers did not show any statistical difference in complex groups. Conclusion: The Pd(II)-complex seems to have a strong anticancer activity on EAC by inducing apoptosis via both suppression of proliferation and activation of apoptosis in vivo, similar to the effects of cisplatin and paclitaxel.