title: Insights into the mechanisms underlying the antitumor activity of an oxidovanadium(IV) compound with the antioxidant naringenin. Albumin binding studies.
abstract: 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 100 μM against lung (A549) and breast (SKBr3 and MDAMB231) cancer cell lines. Furthermore, a newly-synthesized and characterized complex of naringenin and oxidovanadium(IV) ([V(IV)O(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.
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115-C.C.962-B1900AVV, 1900 La Plata, Argentina.
authors.forename: María S
authors.initials: MS
authors.lastname: Islas
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115-C.C.962-B1900AVV, 1900 La Plata, Argentina.
authors.forename: Luciana G
authors.initials: LG
authors.lastname: Naso
authors.affiliation: Departamento de Química Inorgánica, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, P.O. Box 644, 48080 Bilbao, Spain; BCMaterials, Parque científico y Tecnológico de Bizkaia, Edificio 500-1, 48160 Derio, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Lezama
authors.affiliation: Innoprot SL, Parque científico y Tecnológico de Bizkaia, Edificio 502-P1, 48160 Derio, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Valcarcel
authors.affiliation: Innoprot SL, Parque científico y Tecnológico de Bizkaia, Edificio 502-P1, 48160 Derio, Spain.
authors.forename: Clarisa
authors.initials: C
authors.lastname: Salado
authors.affiliation: Innoprot SL, Parque científico y Tecnológico de Bizkaia, Edificio 502-P1, 48160 Derio, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Roura-Ferrer
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115-C.C.962-B1900AVV, 1900 La Plata, Argentina.
authors.forename: Evelina G
authors.initials: EG
authors.lastname: Ferrer
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115-C.C.962-B1900AVV, 1900 La Plata, Argentina. Electronic address: williams@quimica.unlp.edu.ar.
authors.forename: Patricia A M
authors.initials: PA
authors.lastname: Williams
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D001665:Binding Sites; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects; D044950:Flavanones / Q000737:chemistry*; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D014639:Vanadium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D044950:Flavanones; D009942:Organometallic Compounds; D014639:Vanadium; D012710:Serum Albumin, Bovine; C005273:naringenin
keywords: Antioxidant properties; BSA binding; Mechanism cytotoxic action; Naringenin; Oxidovanadium(IV) complexes