Insights into the mechanisms underlying the antitumor activity of an oxidovanadium(IV) compound with the antioxidant naringenin. Albumin binding studies

• Published in: Journal of inorganic biochemistry 2015-08, Vol.149, p.12-24
• Main Authors: Islas, María S., Naso, Luciana G., Lezama, Luis, Valcarcel, María, Salado, Clarisa, Roura-Ferrer, Meritxell, Ferrer, Evelina G., Williams, Patricia A.M.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antioxidant properties; Antioxidants - chemistry; Antioxidants - pharmacology; Apoptosis; Binding Sites; BSA binding; Cell Cycle Checkpoints; Cell Line, Tumor; DNA Damage; Epithelial Cells - drug effects; Flavanones - chemistry; Humans; Mechanism cytotoxic action; Naringenin; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Oxidovanadium(IV) complexes; Protein Binding; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - metabolism; Vanadium - chemistry
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.04.011

Naringenin, a natural antioxidant present in grapefruit, oranges and the skin of tomatoes showed low antioxidant properties among other flavonoids due to its structural characteristics. Since many flavonoids were shown to have cell-killing and antioxidant activities, naringenin was investigated herein. In parallel with its antioxidant activities the flavonoid showed very low cytotoxicity at concentrations up to 100μM against lung (A549) and breast (SKBr3 and MDAMB231) cancer cell lines. Furthermore, a newly-synthesized and characterized complex of naringenin and oxidovanadium(IV) ([VIVO(nar)2]·2H2O, VOnar, with weak ferromagnetic coupling) was also studied. As a result, VOnar acted as a better compound on cell-killing and antioxidant activities (in vitro) than naringenin. The anti-proliferative effect of VOnar was accompanied by reactive oxygen species (ROS) generation, cell membrane and DNA damages, cell cycle arrest, caspase 3/7 activation and mitochondrial potential reduction. The higher parameters observed for the MDAMB231 cell line have been related to its low glutathione (GSH) content. The assays of the interaction of bovine serum albumin (BSA) with the complex showed the affinity of protein toward it and that there is only one binding site on the BSA molecule. However, metal complexation decreased the binding affinity to BSA of naringenin probably due to a steric hindrance of the complex. A polynuclear oxidovanadium(IV) naringenin complex (weak ferromagnetism) has been obtained. Different cytotoxicity against human lung and breast cancer cells and moderate BSA binding were found. An intrinsic pathway in induced apoptosis was determined for VOnar in breast cell lines displaying selective effects according to their basal antioxidant machinery (GSH). [Display omitted] •Polynuclear oxidovanadium(IV) naringenin complex (weak ferromagnetism) is reported.•Different cytotoxicity against human lung and breast cancer cell lines was found.•Mechanistic studies of the antitumoral action were performed.•Higher cytotoxicity was associated with cells with low antioxidant machinery (GSH).•The complex showed moderate BSA binding.