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

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.

Wound healing activity of silibinin in mice

“…[31] Previous works, as well as preliminary studies in our laboratory show antioxidant property of silibinin. [32] Wounds are usually accompanied by pain as well as reddening and edema of the surrounding tissues. These are all classical symptoms of inflammation.…”

Behavior of the potential antitumor VIVO complexes formed by flavonoid ligands. 2. Characterization of sulfonate derivatives of quercetin and morin, interaction with the bioligands of the plasma and preliminary biotransformation studies

“…Over the last years, V IV O complexes formed by flavonoid ligands have been extensively studied for their potential antitumor properties; in particular, they have been demonstrated to be effective against osteosarcoma cell lines [29][30][31][32][33][34][35]. The bis-chelated V IV O species formed by quercetin and morin are very effective against the proliferation of tumoral osteoblast-like cells (UMR106) [29] and breast cancer cells (T47D and SKBR3) [33].…”

In vitro and in vivo anticancer efficacy of silibinin against human pancreatic cancer BxPC-3 and PANC-1 cells

“…We did not observe any adverse health effect in mice as monitored by body weight gain and diet consumption. In several studies, silibinin has been found to be non-toxic to normal or non-neoplastic cells or mice [28][29][30]23]. Overall, these findings suggest for in vivo antitumor efficacy of silibinin, although with different extent, against human pancreatic cancer cells.…”