title: 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(η(6)-p-cym)Cl{dpa(CH2)4COOEt}][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(η(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.
authors.affiliation: Institute of Inorganic Chemistry, Leipzig University, Johannisallee 29, D-04103 Leipzig, Germany; Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle (Saale) Germany.
authors.forename: Goran N
authors.initials: GN
authors.lastname: Kaluđerović
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Krajnović
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Miljana
authors.initials: M
authors.lastname: Momcilovic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stosic-Grujicic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Mijatović
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Maksimović-Ivanić
authors.affiliation: Institute of Inorganic Chemistry, Leipzig University, Johannisallee 29, D-04103 Leipzig, Germany.
authors.forename: Evamarie
authors.initials: E
authors.lastname: Hey-Hawkins
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053148:Caspase 3 / Q000172:deficiency; D002478:Cells, Cultured; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000081007:Cymenes; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D012428:Ruthenium / Q000737:chemistry*; D013154:Spleen / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D000081007:Cymenes; D016207:Cytokines; C000611746:chloro(eta6-p-cymene)(2,2'-dipyridylamine)ruthenium(II); D012428:Ruthenium; D053148:Caspase 3
keywords: Anticancer drugs; Cisplatin; Cytokines; Immune cells; Ruthenium(II)