Ruthenium(II) p-cymene complex bearing 2,2 `-dipyridylamine targets caspase 3 deficient MCF-7 breast cancer cells without disruption of antitumor immune response

Abstract

{[}Ru(eta(6)-p-cym)Cl\{dpa(CH2)(4)COOEt\}]{[}PF6] (cym = cymene; dpa = 2,2'-dipyridylamine; complex 2) was prepared and characterized by elemental analysis, IR and multinuclear NMR spectroscopy, as well as ESI-MS and X-ray structural analysis. The structural analog without a side chain {[}Ru(eta(6)-p-cym)Cl(dpa)]{[}PF6] (1) as well as 2 were investigated in vitro against 518A2, SW480, 8505C, A253 and MCF-7 cell lines. Complex 1 is active against all investigated tumor cell lines while the activity of compound 2 is limited only to caspase 3 deficient MCF-7 breast cancer cells, however, both are less active than cisplatin. As CD4(+)Th cells are necessary to trigger all the immune effector mechanisms required to eliminate tumor cells, besides testing the in vitro antitumor activity of 1 and 2, the effect of ruthenium(II) complexes on the cells of the adaptive immune system have also been evaluated. Importantly, complex 1 applied in concentrations which were effective against tumor cells did not affect immune cell viability, nor did exert a general immunosuppressive effect on cytokine production. Thus, beneficial characteristics of 1 might contribute to the overall therapeutic properties of the complex. (C) 2015 Elsevier Inc. All rights reserved.