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
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
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DOI：
10.1007/s00775-010-0652-z
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发表时间：
2010-04
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通讯作者：
Luciana G. Naso;E. Ferrer;L. Lezama;T. Rojo;S. Etcheverry;P. Williams
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文献类型：
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作者：
Luciana G. Naso;E. Ferrer;L. Lezama;T. Rojo;S. Etcheverry;P. Williams
合成了新的配合物[VO(白杨素)2EtOH]2(VOchrys)，并对其进行了表征。进行了傅立叶变换红外光谱、紫外-可见光谱、漫反射光谱、EPR光谱以及元素分析和热性能测试。在溶液中，EPR光谱可以检测到不同的物种，这是配体与金属的比例的函数。用分光光度滴定法测定了在pH值为5时形成的络合物的化学计量比。由于黄酮类化合物是天然的抗氧化剂，研究了不同自由基对白杨素及其钒(IV)络合物的抗氧化作用。白杨素及其络合物不能很大程度地降低超氧阴离子自由基和1，1-二苯基-2-苦基肼自由基水平。相反，它们对2，2′-azinobis(3-ethylbenzothiazoline-6-sulfonic酸性二铵盐自由基阳离子和对VOchrys的OH·自由基具有较强的清除能力。考虑到它们的选择性抗氧化性能，我们研究了这些化合物在两种成骨细胞样细胞培养中的生物活性。白杨素和VOchrys对MC3T3E1正常成骨细胞和UMR106肿瘤细胞的增殖均有抑制作用，且呈剂量-反应关系，对UMR106肿瘤细胞的抑制作用更强。在这两种细胞系中评估了ROS的产生，白杨素的抗增殖作用与ROS水平的增加之间可以建立相关性。该复合体不产生二氢罗丹明123技术可以检测到的ROS类型，因此抗增殖作用可能归因于其他自由基的形成，如超氧化物的形成，而这一探针没有检测到。这些形态变化与这些变化是一致的。
The new complex [VO(chrysin)2EtOH]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.