title: Antioxidant, anticancer activities and mechanistic studies of the flavone glycoside diosmin and its oxidovanadium(IV) complex. Interactions with bovine serum albumin.
abstract: The natural antioxidant flavonoid diosmin, found in citric fruits, showed low antioxidant properties among other flavonoids due to its structural characteristics and low cytotoxicity against lung (A549) and breast (T47D, SKBR3 and MDAMB231) cancer cell lines. The anticancer behavior has been improved by the metal complex generated with the flavonoid and the oxidovanadium(IV) ion. This new complex, [VO(dios)(OH)3]Na5·6H2O (VOdios), has been synthesized and characterized both in solid and solution states. The interaction of the metal ion through the sugar moiety of diosmin precluded the improvement of the antioxidant effects. However, the cell-killing effects tested in human lung A549 and breast T47D, SKBR3 and MDAMB231 cancer cell lines, were enhanced by complexation. The anti-proliferative effects on the human lung cancer cell line were accompanied by cellular ROS generation and an increase in cytoplasm condensation. The breast cancer cell lines did not produce caspase3/7 activation, mitochondrial potential reduction and ROS generation. Therefore, a non-apoptotic form of cell death in a caspase- and oxidative stress-independent manner has been proposed. The protein binding ability has been monitored by the quenching of tryptophan emission in the presence of the compounds using bovine serum albumin (BSA) as a model protein. Both compounds could be distributed and transported in vivo and the complex displayed stronger binding affinity and higher contributions to the hydrogen bond and van der Waals forces.
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Bv. 120 N° 1465 (62 y 63), 1900 La Plata, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Naso
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Bv. 120 N° 1465 (62 y 63), 1900 La Plata, Argentina.
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Martínez
authors.affiliation: Departamento de Química Inorgánica, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, PO 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: 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: María
authors.initials: M
authors.lastname: Valcarcel
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Bv. 120 N° 1465 (62 y 63), 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, Bv. 120 N° 1465 (62 y 63), 1900 La Plata, Argentina. Electronic address: williams@quimica.unlp.edu.ar.
authors.forename: Patricia A M
authors.initials: PAM
authors.lastname: Williams
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D004145:Diosmin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014639:Vanadium / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D056831:Coordination Complexes; D017382:Reactive Oxygen Species; D014639:Vanadium; D012710:Serum Albumin, Bovine; D004145:Diosmin; D020169:Caspases
keywords: Anticancer; Antioxidant; BSA binding; Diosmin; Oxidovanadium(IV) complexes