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Antioxidant,DNA cleavage,and cellular effects of silibinin and a new oxovanadium(IV)/silibinin complex
Authors:Luciana G. Naso  Evelina G. Ferrer  Nataliya Butenko  Isabel Cavaco  Luis Lezama  Teófilo Rojo  Susana B. Etcheverry  Patricia A. M. Williams
Affiliation:1.Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Facultad de Ciencias Exactas,Universidad Nacional de La Plata,La Plata,Argentina;2.Departamento de Química, Bioquímica e Farmácia,Universidade do Algarve,Faro,Portugal;3.Centro de Química Estrutural, Instituto Superior Técnico, TU Lisbon,Lisbon,Portugal;4.Departamento de Química Inorgánica, Facultad de Ciencia y Tecnología,Universidad del País Vasco,Bilbao,Spain;5.Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas,Universidad Nacional de La Plata,La Plata,Argentina
Abstract:A new complex of the oxovanadium(IV) cation with the flavolignan silibinin has been synthesized and characterized. Vanadium compounds show interesting biological and pharmacological properties and some of them display antitumoral actions. Flavonoids are part of a larger group of antioxidant compounds called polyphenols which may inhibit the proliferation and growth of cancer cells. The antioxidant and antitumoral effects of silibinin and its oxovanadium(IV) complex were investigated. Silibinin acted as a very strong antioxidant and its complexation with oxovanadium(IV) improved this behavior. Besides, the generation of reactive oxygen species (ROS) by this compound was favored in tumoral (UMR106) cells and correlated with the deleterious behavior in the proliferation of this cell line. Conversely, silibinin did not exert any effect on the proliferation of normal osteoblasts (MC3T3E1). The cytotoxic action and ROS generation of the oxovanadium(IV) complex was more effective in tumoral cells. This behavior was not consistent with cleaving DNA of plasmid DNA pA1 because no significant cleaving activity was observed in both cases. These results suggest that the main deleterious mechanisms may take place through cytotoxic effects more than genotoxic actions. A comparison with our own findings on the behavior of other flavonoids and their vanadyl(IV) complex has also been performed.
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