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: Goran N Kaluđerović, Tamara Krajnović, Miljana Momcilovic, Stanislava Stosic-Grujicic, Sanja Mijatović, Danijela Maksimović-Ivanić, Evamarie Hey-Hawkins
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 153 Pg. 315-321 (Dec 2015) ISSN: 1873-3344 [Electronic] United States
• PMID: 26428537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Coordination Complexes
• Cymenes
• Cytokines
• chloro(eta6-p-cymene)(2,2'-dipyridylamine)ruthenium(II)
• Ruthenium
• Caspase 3

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Caspase 3 (deficiency)
• Cells, Cultured
• Coordination Complexes (chemical synthesis, chemistry, pharmacology)
• Cymenes
• Cytokines (genetics, metabolism)
• Humans
• MCF-7 Cells
• Mice
• Mice, Inbred C57BL
• Ruthenium (chemistry)
• Spleen (drug effects)
• T-Lymphocytes, Helper-Inducer (drug effects)