CEQUINOR   05415
CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Platinum(II) complexes based on hidroxyquinoline ligands. Anticancer effects and mechanisms of action in a human osteosarcoma model: structure?activity relationship
Autor/es:
LEÓN IE; MUGLIA CI; MARTÍN-SANTOS C.; ALEMÁN J.; NAVARRO-RANNINGER C.; ETCHEVERRY SB.
Lugar:
Chascomús Buenos Aires
Reunión:
Encuentro; Fourth latin American Meeting on Biological Inorganic Chemistry; 2014
Institución organizadora:
Society of Biological Inorganic Chemistry
Resumen:
Type of presentation: POSTER Platinum(II) complexes based on hidroxyquinoline ligands. Anticancer effects and mechanisms of action in a human osteosarcoma model: structure?activity relationship Leon I.E 1, Muglia CI 2, Martín-Santos C.3, Alemán J.4, Navarro-Ranninger C3, and Etcheverry S.B.1 1 CEQUINOR, Fac. Cs Exactas, UNLP, La Plata, Argentina2 Lisin, Fac. Cs Exactas, UNLP, La Plata, Argentina 3 Dep. Química. Inorgánica, Fac. de Ciencias, UAM, Madrid, Spain. 4 Dep. Química Orgánica, Fac. de Ciencias, UAM, Madrid, Spain Email: iel86@yahoo.com.ar INTRODUCTION Despite the remarkable success of CDDP (cisplatin)1,2 in the treatment of different types of cancers, two major limitations of the drug are remarkable (i) its dose-limiting effects (mainly nephrotoxicity, nausea and vomiting, and high cytotoxicity) and (ii) its inactivity against some of the most frequent human tumor types (e.g. colon and lung cancers). These limitations early stressed the necessity for the search of structural analogues endowed with fewer side effects and capable of overcoming acquired resistance to CDDP. On the other hand, the hydroxyquinolines derivatives have medicinal properties such as antineurodegenerative, antidiabetic anticancer, antioxidant, antimicrobial, anti-inflammatory, and anticancer activities. Regarding the anticancer activity of the hydroxyquinolines, different mechanisms of action have been reported 3. In this work we report the biological effects of two complexes (1 and 2, Fig 1) of platinum(II) with analogous of clioquinol on a human osteosarcoma cell line (MG-63 ATCC CRL-1427). EXPERIMENTAL METHODS Synthesis of platinum complexes The complexes 1 and 2 were synthesized and identified according to previously reported results 4. Cell line and growth conditions MG-63 human osteosarcoma cells (CRL1427?) were grown in DMEM containing 10 % FBS, 100 U/mL penicillin and 100 μg/mL streptomycin at 37 ° C in 5% CO2 atmosphere. MTT assay Briefly, cells were seeded in a 96-multiwell dish, allowed to attach for 24 h and treated with different concentrations of complexes at 37 °C for 24 h. After that, the medium was changed and the cells were incubated with 0.5 mg/mL MTT under normal culture conditions for 3 h. Cell viability was marked by the conversion of the tetrazolium salt MTT to a colored formazan by mitochondrial dehydrogenases. Determination of Reactive Oxygen Species (ROS) Production Oxidative stress in osteoblasts was evaluated by measurement of intracellular production of reactive oxygen species (ROS) after incubation of the cell monolayers with different concentrations of the complex during 4 h at 37 °C. ROS generation was determined by oxidation of DHR-123 to rhodamine by spectrofluorescence. Measurement of the exposure of phosphatidyl serine (PS) by Annexin V-FITC/PI Staining Cells in early and late stages of apoptosis were detected with Annexin V-FITC and Propidium Iodide (PI) staining. Cells were analyzed using flow cytometer CyAnTM ADP (Beckman Coulter, USA) and Summit v 4.3 software. Statistical Analysis The results are expressed as the mean ± the standard error of the mean (SEM). Statistical differences were analyzed using the analysis of variance method (ANOVA) followed by the test of least significant difference (Fisher). RESULTS AND DISCUSSION The results showed that after 6 h, complex 2 diminished cell viability in the range of 10-100 µM while compound 1 did not show any effects on cell viability in the same range of concentrations ( Fig 2 , p
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