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Background/aim: [Pd(sac)(terpy)](sac)•4H2O (sac=saccharinate and terpy=2,2':6',2"-terpyridine) is newly-synthesized palladium(II) (Pd) complex. We investigated the antiproliferative and apoptotic effects of this complex on Ehrlich ascites carcinoma (EAC)., Materials and Methods: EAC cells were administered to 33 Balb/c mice. Mice were divided randomly into four groups: control, cisplatin, Pd(II) complex and paclitaxel. Control group animals received 0.9% NaCl; other groups received treatments cisplatin, Pd(II) complex and paclitaxel on days 7 and 12. At day 14, animals were sacrificed. Expression of active caspase-3, p53 and proliferating cell nuclear antigen (PCNA) was investigated and apoptosis was evaluated by terminal deoxynucleotidyltransferase (TdT)-mediated nick-end labelling (TUNEL) technique., Results: Expression of p53 and PCNA were found to be decreased (p<0.0001), cells with active caspase-3 and TUNEL-positive cells were found to be increased (p<0.0001) in all treatment groups., Conclusion: Like cisplatin and paclitaxel, this Pd(II) complex has a strong anticancer activity against EAC by inducing apoptosis and suppressing proliferation in vivo., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The anti-growth effect of a palladium(II) complex-[PdCl(terpy)](sac)·2H2O] (sac=saccharinate, and terpy=2,2':6',2″-terpyridine)-was tested against human breast cancer cell lines, MCF-7 and MDA-MB-231. Anti-growth effect was assayed by the MTT and ATP viability assays in vitro and then confirmed on Balb/c mice in vivo. The mode of cell death was determined by both histological and biochemical methods. The Pd(II) complex had anti-growth effect on a dose dependent manner in vitro and in vivo. The cells died by apoptosis as evidenced by the pyknotic nucleus, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active caspase-3. These results suggest that the palladium(II) saccharinate complex of terpyridine represents a potentially active novel complex for the breast cancer treatment, thus warrants further studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Breast cancer is one of the leading cancer types in terms of morbidity and mortality globally. Although cisplatin has a strong anti-tumor effect, studies show that it is extremely toxic, causing nephrotoxicity and ototoxicity. To resolve these concerns, multinuclear metal complexes are synthesized. The synthesis of these complexes is crucial due to their high dna binding affinity and cytotoxic effect. Material and Method: The cytotoxic effects of dinuclear Pd (II) complex on breast cancer cell lines(MCF-7, MDAMB- 231) and healthy breast cell line(MCF-10F) were investigated. SRB and ATP viability tests were performed to determine the effect of the Pd(II) complex on cell viability. The presence of apoptosis in breast cancer cells was demonstrated by various staining methods, flow cytometry and immunoblotting. Colony formation, invasion, and migration assays were performed to evaluate the effect of the complex on metastasis. Results: The anti-cancer effect of the Pd (II) complex on MCF-7 was detected at low doses, while the cytotoxic effect on MCF-10F was significantly less. As a result of flow cytometry experiments, increased caspase3/7 levels and positive annexinV staining were reported in both cell lines. The presence of apoptosis was elucidated regardless of p53 expression in MCF-7 and MDA-MB-231 due to increased TNFR1 and TRADD expression with caspase8 cleavage and increased Bcl-2 inactivation with loss of mitochondiral membrane potential. Conclusion: The Dinuclear Pd (II) complex, which is acknowledged to induce both extrinsic and intrinsic apoptosis, may be used as a promising treatment option on breast cancer, it was concluded that further in vivo experiments should be performed. [ABSTRACT FROM AUTHOR]

Because of the high mortality and morbidity rate of breast cancer, successful management of the disease requires synthesis of novel compounds. To this end, ongoing attempts to create new candidates include synthesis of multinuclear metal complexes. The high DNA binding affinity and cytotoxic activity of these complexes makes them promising as breast cancer treatments. This study investigated anti-growth/cytotoxic effect of the dinuclear Pd(II) complex on breast cancer cell lines (MCF-7, MDA-MB-231) using various methods of staining, flow cytometry, and immunoblotting. The study conducted colony formation, invasion, and migration assays were to assess the effect of the complex on metastasis. Increased caspase-3/7 levels and positive annexin V staining were observed in both cell lines, proving apoptosis. Altered TNFR1 and TRADD expression with caspase-8 cleavage followed by BCL-2 inactivation with loss of mitochondrial membrane potential confirmed the presence of apoptosis in MCF-7 and MDA-MB-231, regardless of p53 expression status. The results implied anti-migration properties. Finally, the study used the CAM assay to assess antiangiogenic properties and showed that the complex inhibited angiogenesis. The study concluded the dinuclear Pd(II) complex warrants further in vivo experiments to show its potential in the treatment of breast cancer. [Display omitted] • The dinuclear Pd(II) complex triggers caspase-mediated apoptosis, which appears to be caused by the accumulation of ROS and a decline in mitochondrial membrane potential. • The ability of MDA-MB-231 cells to migrate and invade is inhibited by the dinuclear Pd(II) complex. • The dinuclear Pd(II) complex is thought to have anti-angiogenic properties and this is confirmed by the CAM assay. [ABSTRACT FROM AUTHOR]

The current study assessed the effects of the thalidomide and palladium (II) saccharinate complex of terpyridine on the suppression of angiogenesis-mediated cell proliferation. The viability was assessed after treatment with palladium (II) complex (1.56–100 μM) and thalidomide (0.1–400 μM) alone by using ATP assay for 48 h. Palladium (II) complex was found to inhibit growth statistically significant in a dose-dependent manner in HUVECs and promoted PARP-1 cleavage through the production of ROS. On the other hand, thalidomide did not cause any significant change in cell viability. Moreover, cell death was observed to be manifested as late apoptosis due to Annexin V/SYTOX staining after palladium (II) complex treatment however, thalidomide did not demonstrate similar results. Thalidomide and palladium (II) complex also suppressed HUVEC migration and capillary-like structure tube formation in vitro in a time-dependent manner. Palladium (II) complex (5 mg/ml) treatment showed a strong antiangiogenic effect similar to positive control thalidomide (5 mg/ml) and successfully disrupted the vasculature and reduced the thickness of the vessels compared to control (agar). Furthermore, suppression of autophagy enhanced the cell death and anti-angiogenic effect of thalidomide and palladium (II) complex. We also showed that being treated with thalidomide and palladium (II) complex inhibited phosphorylation of the signaling regulators downstream of the VEGFR2. These results provide evidence for the regulation of endothelial cell functions that are relevant to angiogenesis through the suppression of the FAK/Src/Akt/ERK1/2 signaling pathway. Our results also indicate that PLC-γ1 phosphorylation leads to activation of p-Akt and p-Erk1/2 which cause stimulation on cell proliferation at lower doses. Hence, we demonstrated that palladium (II) and thalidomide can induce cell death via the Erk/Akt/PLCγ signaling pathway and that this pathway might be a novel mechanism. [Display omitted] • Palladium (II) complex exerted antiangiogenic effect by promoting apoptosis through ROS activation in HUVECs. • Blockade of autophagy by palladium (II) complex could enhance the sensitivity of HUVECs to angiogenesis. • Palladium (II) complex reduced angiogenic responses by blocking Erk/Akt/PLC-γ1/FAK signaling pathways. • Palladium (II) complex might be a novel angiogenesis inhibitör. [ABSTRACT FROM AUTHOR]