CEQUINOR   05415
CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Towards the mechanism of action of [Cu(AlaPhe)] as antitumoral
Autor/es:
FACCHIN G; ETCHEVERRY SB; BASTIAN G; TORRE, MARÍA HELVECIA
Lugar:
Granada
Reunión:
Conferencia; 11th Europewn Biological Inorganic Chemistry Conference; 2012
Resumen:
As a part of our research on metal-based drugs our group synthesized and structurally characterized in solid state and in water solution several copper complexes with dipeptides [1][2]. Their SOD-like activity, ROS production ability and the interaction with DNA (by EPR and CD), were evaluated. From these studies the [Cu(AlaPhe)]•1/2 H2O was the complex which showed the best performance. Therefore, it was selected to perform cytotoxic studies with different human tumoral cell lines from lung (A549), colon (HT29), ovary (HeLa) and prostate (LNCap) using MTT assay. With the aim of obtaining information about the mechanism of action, the copper concentration in these cell lines and in their nucleus was determined. Cells were treated with a 50µM complex solution during 4 days. Nucleuses were harvested after treatment with KCl 0.075M during 30min at 37°C and copper was measured by Atomic Absorption Spectrometry.+ The IC50 after 72h incubation were: 75 µM (A549S), 80 µM (HeLa), 125 µM (HT29) and 75 µM (LNCap). Cu content in total cells (red) and in nucleus (yellow) after 4 days treatment and 1 day post treatment, incubated in a medium without copper, is presented in the graph. After treatment near 70% of Cu is in the cell nucleus and after 1 day of post treatment 65-80% of Cu was released but some part of copper is fixed by DNA, in agreement with the previews results obtained by EPR and CD. Besides, cytotoxic studies with osteoblast and osteosarcome cells showed selectivity for the tumoral cells. This work shows the relationship between the spectroscopic and cytotoxic results and indicates that a continuous treatment is necessary to achieve a constant cooper level in cells. Acknowledgements: PEDECIBA Química and CYTED 209RT0380 References:[1] G. Facchin, E. Kremer, D. Barrios, S. Etcheverry, A. Costa-Filho, M.H.Torre, Polyhedron 2009: 28, 2329. [2] E.D. Viera, N.M.C. Casado, G. Facchin, M.H. Torre, A.J. Costa-Filho, R. Calvo, Inorg. Chem. 2006: 45, 8.
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