Biological effects of a complex of vanadium(V) with salicylaldehyde semicarbazone in osteoblasts in culture: Mechanism of action |
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Authors: | Josefina Rivadeneira Daniel A Barrio Dinorah Gambino Susana B Etcheverry |
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Institution: | a Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas, UNLP. 47 y 115 1900 La Plata, Argentina b CEQUINOR (CONICET-UNLP), Facultad de Ciencias Exactas, UNLP, La Plata, Argentina c Facultad de Química, Universidad de la República, Montevideo, Uruguay d Departamento de Química, Facultad de Ciencias Exactas, UNLP, La Plata, Argentina |
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Abstract: | Vanadium compounds display important pharmacological actions in vivo and in vitro systems. Semicarbazones are versatile ligands with therapeutic effects. Herein, we report the effects of VVO2(salicylaldehydesemicarbazone) (V(V)-Salsem) on two osteoblast cell lines in culture (MC3T3-E1 and UMR106). V(V)-Salsem inhibited cell proliferation in a dose response manner. At 100 μM, the complex caused an inhibition of ca. 48% and 38% for the normal and the tumoral osteoblasts, respectively (p < 0.001). This inhibition could be partially reversed to 35% and 28% by NAC (N-acetylcysteine) and a mixture of vitamins E and C. Changes in cell proliferation correlated with morphological alterations and the disruption of actin cytoskeleton fibers. The complex also enhanced the level of ROS (reactive oxygen species) up to ca. 100% over basal in both cell lines. Activation of ERK signalling cascade was also observed. These events led to apoptosis (up to 44% in MC3T3-E1 and 33% in UMR106 cells). Scavengers of ROS and inhibitors of ERK cascade allowed to elucidate the mechanisms involved in the cytotoxicity. In conclusion, V(V)-Salsem displayed cytotoxic effects on osteoblasts in culture through the production of free radicals and the activation of ERK cascade. These mechanisms triggered the apoptotic events that conveyed to cell death. |
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Keywords: | Vanadium Semicarbazones Osteoblasts Cytotoxicity Oxidative stress Actin fibers |
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