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

• Published in: Journal of biological inorganic chemistry 2011-04, Vol.16 (4), p.653-668
• Main Authors: Naso, Luciana G., Ferrer, Evelina G., Butenko, Nataliya, Cavaco, Isabel, Lezama, Luis, Rojo, Teófilo, Etcheverry, Susana B., Williams, Patricia A. M.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Biochemistry; Biomedical and Life Sciences; Cell Line, Tumor; Cell Proliferation - drug effects; DNA Cleavage - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Electron Spin Resonance Spectroscopy; Life Sciences; Microbiology; Molecular Structure; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Original Paper; Plasmids - drug effects; Rats; Reactive Oxygen Species - metabolism; Silymarin - chemistry; Silymarin - pharmacology; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Vanadates - chemistry; Vanadates - pharmacology
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-011-0769-8

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.