Antioxidant, DNA cleavage, and cellular effects of silibinin and a new oxovanadium(IV)/silibinin complex

• DOI: 10.1007/s00775-011-0769-8
• Publication Date: 2011-03-11T16:25:40Z
• Authors: Luciana G. Naso; Evelina G. Ferrer; Nataliya Butenko; Isabel Cavaco; Luis Lezama; Teófilo Rojo; Susana B. Etcheverry; Patricia A. M. Wi...
• Keywords: Antineoplastic Agents; Antitumoral; Antioxidants; Structure-Activity Relationship; 03 medical and health sciences; Silibinin; Cell Line, Tumor; Spectroscopy, Fourier Transform Infrared; Organometallic Compounds; Animals; DNA Cleavage; Oxovanadium(IV); Cell Proliferation; 0303 health sciences; Osteoblasts; Dose-Response Relationship, Drug; Molecular Structure; Electron Spin Resonance Spectroscopy; Química; Rats; 3. Good health; Silybin; Spectrophotometry, Ultraviolet; Antioxidant; Drug Screening Assays, Antitumor; Vanadates; Reactive Oxygen Species; Plasmids; Silymarin

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.