Browsing by Author "Etcheverry, Susana B."
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- Antioxidant, DNA cleavage, and cellular effects of silibinin and a new oxovanadium(IV)/silibinin complexPublication . Naso, Luciana G.; Ferrer, Evelina G.; Butenko, Nataliya; Cavaco, Isabel Maria Palma Antunes; Lezama, Luis; Rojo, Teófilo; Etcheverry, Susana B.; Williams, Patricia A. M.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 andROSgeneration of the oxovanadium(IV) complex was more effective in tumoral cells. This behavior was not consistent with cleavingDNA 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.
- Cyto- and genotoxicity of a vanadyl(IV) complex with oxodiacetate in human colon adenocarcinoma (Caco-2) cells: potential use in cancer therapyPublication . Di Virgilio, Ana L.; Rivadeneira, Josefina; Muglia, Cecilia I.; Reigosa, Miguel A.; Butenko, Nataliya; Cavaco, Isabel Maria Palma Antunes; Etcheverry, Susana B.The complex of vanadyl(IV) cation with oxodiacetate, VO(oda) caused an inhibitory effect on the proliferation of the human colon adenocarcinoma cell line Caco-2 in the range of 25–100 lM (P\0.001). This inhibition was partially reversed by scavengers of free radicals. The difference in cell proliferation in the presence and the absence of scavengers was statistically significant in the range of 50–100 lM (P\0.05). VO(oda) altered lysosomal and mitochondria metabolisms (neutral red and MTT bioassays) in a dose–response manner from 10 lM(P\0.001). Morphological studies showed important transformations that correlated with the disassembly of actin filaments and a decrease in the number of cells in a dose response manner. Moreover, VO(oda) caused statistically significant genotoxic effects on Caco-2 cells in the low range of concentration (5–25 lM) (Comet assay). Increment in the oxidative stress and a decrease in the GSH level are the main cytotoxic mechanisms of VO(oda). These effects were partially reversed by scavengers of free radicals in the range of 50–100 lM (P\0.05). Besides, VO(oda) interacted with plasmidic DNA causing single and double strand cleavage, probably through the action of free radical species. Altogether, these results suggest that VO(oda) is a good candidate to be evaluated for alternative therapeutics in cancer treatment.