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Trieste, Italy

Hudej R.,University of Ljubljana | Hudej R.,BIA Separations d.o.o. | Miklavcic D.,University of Ljubljana | Cemazar M.,Institute of Oncology Ljubljana | And 10 more authors.
Journal of Membrane Biology | Year: 2014

To increase electrochemotherapy (ECT) applicability, the effectiveness of new drugs is being tested in combination with electroporation. Among them two ruthenium(III) compounds, (imH)[trans-RuCl4(im)(DMSO-S)] (NAMI-A) and Na[trans-RuCl4(ind)2] (KP1339), proved to possess increased antitumor effectiveness when combined with electroporation. The objective of our experimental work was to determine influence of electroporation on the cytotoxic and antitumor effect of a ruthenium(III) compound with hampered transmembrane transport, (imH)[trans-RuCl4(im)2] (KP418) in vitro and in vivo and to determine changes in metastatic potential of cells after ECT with KP418 in vitro. In addition, platinum compound cisplatin (CDDP) and ruthenium(III) compound NAMI-A were included in the experiments as reference compounds. Our results show that electroporation leads to increased cellular accumulation and cytotoxicity of KP418 in murine melanoma cell lines with low and high metastatic potential, B16-F1 and B16-F10, but not in murine fibrosarcoma cell line SA-1 in vitro which is probably due to variable effectiveness of ECT in different cell lines and tumors. Electroporation does not potentiate the cytotoxicity of KP418 as prominently as the cytotoxicity of CDDP. We also showed that the metastatic potential of cells which survived ECT with KP418 or NAMI-A does not change in vitro: resistance to detachment, invasiveness, and re-adhesion of cells after ECT is not affected. Experiments in murine tumor models B16-F1 and SA-1 showed that ECT with KP418 does not have any antitumor effect while ECT with CDDP induces significant dose-dependent tumor growth delay in the two tumor models used in vivo. © 2014, Springer Science+Business Media New York.

Quiroga A.G.,Autonomous University of Madrid | Ramos-Lima F.J.,Autonomous University of Madrid | Alvarez-Valdes A.,Autonomous University of Madrid | Font-Bardia M.,University of Barcelona | And 4 more authors.
Polyhedron | Year: 2011

We have reported the synthesis and characterization of two new trans platinum complexes in the phosphane series, where the phosphane ligand is triphenylphosphine [P(Ph)3] and the group in the trans configuration is represented by chiral aliphatic amines, (racemic in complex 1 and S-NH 2CH2CH(CH3)CH2CH3 in complex 2). The anti-proliferative activity detected in tumor cells treated with the two new complexes is more pronounced when the aliphatic amine is racemic compared to the S-enantiomer. Moreover, for both compounds, the activity is fast after cell exposure and, unlike that of cisplatin, virtually independent of the duration of cell challenge. © 2011 Elsevier Ltd. All rights reserved.

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