Vanadium(V) and Cu(II) complexes: evaluation of their antitumoral potentiality.

LEÓN I.E, ANA L. DIVIRGILIO, D.A, BARRIO G. ARRAMBIDE. EDURDO SANTI, D. GAMBINO, M. TORRE, SB ETCHEVERRY

Granada

Conferencia; 11th European of Biological Inorganic Chemistry (EUROBIC 11); 2012

Metalic ions are essential for health since many diseases are related to their status in the organisms. Metal-pharmaceuticals used in the treatments of different pathologies such as tumors, are organic compounds coordinated with metals. Vanadium compounds exert insulin mimetic actions, as well as osteogenic and antitumoral effects, both in vivo and in vitro [1]. In bone tissue, vanadium derivatives modulate cell proliferation and differentiation. On the other hand, another interesting biometal is copper which participate in essential biological functions in different enzymatic reactions [2]. Besides, copper compounds display interesting anti-inflammatory properties and for this reason they also behave as antitumoral agents [3]. In the frame of a research project devoted to study the potential pharmacological effects of vanadium and copper metallodrugs, we present herein the results of the effects of two vanadium(V) ternary complexes with hydroxylamido and aminoacids: [VO(NH2O)2(val)] and [VO(NH2O)2(met)] [4], and of two copper(II) complexes with saccharinate (Sac) and aminoacids: [Cu(Sac)2(H2O)4].2H2O and [Na2Cu(Sac)2(Gln)2].1.5H2O. Vanadium complexes were studied in two osteoblast cell lines in culture: MC3T3-E1 derived from mouse calvaria and UMR106 derived from a rat osteosarcoma, as well as in an in vivo model of zebrafish eggs (FET test). Vanadium compounds inhibited cell proliferation (crystal violet bioassay), being more deleterious in MC3T3-E1cells. In this assay, [VO(NH2O)2(met)], was the more potent inhibitor (IC50=5 µM ) in agreement with the FET test. Besides, similar results were obtained by MTT cytotoxicity assay. Genotoxicity investigations showed that [VO(NH2O)2(val)] increased the micronucleus frequency (MN test) in MC3T3-E1cell line from 2.5 µM and from 5 µM in the tumoral cells (p