title: Biological evaluation of morin and its new oxovanadium(IV) complex as antioxidant and specific anti-cancer agents.
abstract: It is known that flavonoids possess, among others, antioxidant and antitumoral properties that depend on their molecular structure. The central objective if this study was to investigate the potential antioxidant and antiproliferative properties of the flavonol morin and its new oxovanadium(IV) complex (VOmor) that was synthesized in order to modify the morin chemical structure. Two osteoblast (UMR106 and MC3T3E1), two breast tumor (T47D and SKBR3) and breast epithelial cell lines in culture were used for the antitumoral determinations. Additionally, a comparative study of their antioxidant capacities using different radicals (DPPH, ABTS(+), OH, O2(-), ROO) was performed. Selected mechanisms of action were studied using the breast cancer cell lines. Results obtained show that morin and its complex behaved as good antioxidant agents for some of the radicals and that the complexation improved the behavior with respect to OH and O2(-) radicals being morin more effective as ROO scavenger. A considerable variation in sensitivity was observed in the breast cancer cells but non-specificity was found for the treatment of osteosarcoma. Moreover, the compounds did not affect the normal proliferation of the breast epithelial mammal cells. The mechanistic studies demonstrated that the complex did not generate reactive oxygen species in the cells (confirming the in vitro studies) and did not produce any damage of DNA. The plasmatic membrane was observed to be damaged only in the SKBR3 cell line. In contrast, the perturbation of the mitochondrial membrane potential and the activation of caspase 3/7 for the breast tumor cells revealed an apoptotic cell death process. All these results collectively suggested that VOmor complex could serve as promising pharmacologically active substance against breast cancer treatment.
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, CC 962 (B1900AVV), 1900 La Plata, Argentina.
authors.forename: Luciana G
authors.initials: LG
authors.lastname: Naso
authors.forename: Luis
authors.initials: L
authors.lastname: Lezama
authors.forename: Teófilo
authors.initials: T
authors.lastname: Rojo
authors.forename: Susana B
authors.initials: SB
authors.lastname: Etcheverry
authors.forename: María
authors.initials: M
authors.lastname: Valcarcel
authors.forename: Meritxell
authors.initials: M
authors.lastname: Roura
authors.forename: Clarisa
authors.initials: C
authors.lastname: Salado
authors.forename: Evelina G
authors.initials: EG
authors.lastname: Ferrer
authors.forename: Patricia A M
authors.initials: PA
authors.lastname: Williams
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000975:Antioxidants / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005419:Flavonoids / Q000737:chemistry*; D006801:Humans; D051379:Mice; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014639:Vanadium / Q000737:chemistry*; D047309:Flavones
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D053148:Caspase 3; D053179:Caspase 7; D056831:Coordination Complexes; D005419:Flavonoids; D017382:Reactive Oxygen Species; D014639:Vanadium; C008548:morin; D047309:Flavones
keywords: 1,1-diphenyl-2-picrylhydrazyl radical; 2,2-azobis(2-amidinopropane) dihydrochloride; 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt; 3-(4,5-methyl-thiazol-2-yl)-2,5diphenyl-tetrazolium bromide; 4′,6′-diamidino-2-phenylindole; 5-(and-6)-chloromethyl-2,7,dichlorodihydrofluorescein diacetate acetyl ester; 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; AAPH; ABTS; CM-H2DCFDA; DAPI; DHR123; DMEM; DMSO; DPPH(); Dulbecco’s modified Eagle’s medium; FBS; H2AX; LDH; MTT; NBT; Natural antioxidant morin; Oxovanadium(IV) complex; PBS; ROI; ROS; Radical scavengers; SOD; TEAC; TMRM; Trolox; Trolox equivalent antioxidant coefficient; Tumor specificity; VOmor; [VO(mor)(2)H(2)O]·5H(2)O; dihydrorhodamine 123; dimethyl sulfoxide; fetal bovine serum; lactate dehydrogenase; nitroblue tetrazolium; phosphate-buffered saline; reactive oxygen species; regions-of-interest; subtype of H2A histone; superoxide dismutase; tetramethyl rhodamine methyl ester