title: Antitumor properties of a vanadyl(IV) complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 in a human osteosarcoma model: the role of oxidative stress and apoptosis.
abstract: Flavonoids, a polyphenolic compound family, and the vanadium compounds have interesting biological, pharmacological, and medicinal properties. We report herein the antitumor actions of the complex [VO(chrysin)2EtOH]2 (VOchrys) on the MG-63 human osteosarcoma cell line. Oxovanadium(IV), chrysin and VOchrys caused a concentration-dependent inhibition of cell viability. The complex was the strongest antiproliferative agent (p < 0.05). Cytotoxicity and genotoxicity studies also showed a concentration effect. Reactive oxygen species (ROS) and the alterations in the GSH/GSSG ratio underlie the main mechanisms of action of VOchrys. Additions of ROS scavengers (vitamin C plus vitamin E) or GSH to the viability experiments demonstrated beneficial effects (p < 0.01). Besides, the complex triggered apoptosis, disruption of the mitochondria membrane potential (MMP), increased levels of caspase 3 and DNA fragmentation measured by the sub-G1 peak in cell cycle arrest experiments (p < 0.01). Collectively, VOchrys is a cell death modulator and a promissory complex to be used in cancer treatments.
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115 (1900), La Plata, Argentina.
authors.forename: I E
authors.initials: IE
authors.lastname: Leon
authors.forename: A L
authors.initials: AL
authors.lastname: Di Virgilio
authors.forename: V
authors.initials: V
authors.lastname: Porro
authors.forename: C I
authors.initials: CI
authors.lastname: Muglia
authors.forename: L G
authors.initials: LG
authors.lastname: Naso
authors.forename: P A M
authors.initials: PA
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Bollati-Fogolin
authors.forename: S B
authors.initials: SB
authors.lastname: Etcheverry
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014638:Vanadates / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D009942:Organometallic Compounds; C043561:chrysin; D014638:Vanadates