Role of oxidative stress in the antitumoral action of a new vanadyl(IV) complex with the flavonoid chrysin in two osteoblast cell lines: relationship with the radical scavenger activity.
The new complex [VO(chrysin)(2)EtOH](2) (VOchrys) has been synthesized and thoroughly characterized. Fourier transform IR, UV-vis, diffuse reflectance, and EPR spectroscopies as well as elemental analysis and thermal measurements were performed. In solution, different species could be detected by EPR spectroscopy as a function of the ligand-to-metal ratio. The stoichiometry of the chelate complex formed at pH 5 was also determined by spectrophotometric titrations. Since flavonoids are natural antioxidant compounds, the antioxidant capacity of chrysin and its vanadyl(IV) complex was investigated using different radicals. Chrysin and its complex were not able to diminish the level of superoxide and 1,1-diphenyl-2-picrylhydrazyl radicals to a great extent. In contrast, they were strong scavengers for 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt radical cations and OH. radicals with a greater potency for VOchrys. Taking into account their selective antioxidant properties, we investigated the bioactivity of these compounds in two osteoblast-like cells in culture. Chrysin and VOchrys caused an inhibition of cell proliferation in MC3T3E1 normal osteoblasts and UMR106 tumor cells in a dose-response manner, with a greater effect in the latter cell line. The generation of reactive oxygen species (ROS) was evaluated in both cell lines and a correlation could be established between the antiproliferative effects of chrysin and the increase in the ROS levels. The complex did not generate types of ROS that can be detected by the dihydrorhodamine 123 technique so the antiproliferative effect may be attributed to the formation of other radicals such as superoxide, which is not detected by this probe. The morphological alterations were in agreement with these changes.
Naso
Luciana
L
Facultad de Ciencias Exactas, Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Universidad Nacional de La Plata, C. Correo 962, 1900, La Plata, Argentina.
Ferrer
Evelina Gloria
EG
Lezama
Luis
L
Rojo
Teófilo
T
Etcheverry
Susana Beatriz
SB
Williams
Patricia
P
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014638:Vanadates / Q000737:chemistry*
D000970:Antineoplastic Agents; D005419:Flavonoids; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C043561:chrysin; D014638:Vanadates