Barrio Daniel A, Cattáneo Elizabeth R, Apezteguía María C, Etcheverry Susana B
Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115 (1900) La Plata, Argentina.
Can J Physiol Pharmacol. 2006 Jul;84(7):765-75. doi: 10.1139/y06-021.
Complexes of vanadyl(IV) with 4 monosaccharides and 5 disaccharides were tested in 2 osteoblast-like cell lines (MC3T3E1 and UMR106). Many complexes caused stimulation of UMR106 proliferation (120% basal) in the range of 2.5 to 25 micromol/L. In the nontransformed osteoblasts, some vanadyl-saccharide complexes stimulated the mitogenesis (115% basal) in the same range of concentration. The glucose and sucrose complexes were the most efficient inhibitory agents (65% and 88% of inhibition vs. basal, respectively) for tumoral cells at 100 micromol/L. The galactose and turanose complexes exerted a similar effect in the nontransformed osteoblasts. On the other hand, all the complexes promoted the phosphorylation of the extracellular regulated kinases (ERKs). All together, these results indicate that the stimulation of ERKs is not the only factor that plays a role in the proliferative effects of vanadium derivatives since some compounds were inhibitory proliferating agents. Cell differentiation was evaluated by alkaline phosphatase specific activity and collagen synthesis in UMR106 cells. All the complexes inhibited alkaline phosphatase activity, with galactose complex as the most effective compound (IC50 = 43 micromol/L). The complex with the trehalose TreVO was the most effective agent to stimulate collagen synthesis (142% basal) and glucose consumption (132% basal). A cytosolic tyrosine protein kinase and the kinase-3 of glycogen synthase seem to be involved in the stimulation of glucose consumption by vanadium derivatives. In this series, only TreVO gathered the characteristics of a good insulin mimetic and osteogenic drug. In addition, this complex was a good promoting agent of nontransformed osteoblast proliferation, whereas it inhibited tumoral osteoblasts. GluVO, the complex with glucose, was also more toxic for tumoral than for nontransformed cells. These 2 vanadium derivatives are good potential antitumoral drugs. All the results suggest that the biological effects of vanadium compounds are a complex phenomenon influenced by the complexation, the dose, and the nature of the ligands and the cells.
对钒（IV）与4种单糖和5种二糖形成的配合物在2种成骨样细胞系（MC3T3E1和UMR106）中进行了测试。许多配合物在2.5至25微摩尔/升的范围内可刺激UMR106细胞增殖（为基础水平的120%）。在未转化的成骨细胞中，一些钒-糖配合物在相同浓度范围内可刺激有丝分裂（为基础水平的115%）。葡萄糖和蔗糖配合物在100微摩尔/升时是对肿瘤细胞最有效的抑制剂（分别抑制基础水平的65%和88%）。半乳糖和松二糖配合物在未转化的成骨细胞中发挥类似作用。另一方面，所有配合物均可促进细胞外调节激酶（ERK）的磷酸化。总体而言，这些结果表明，ERK的刺激并非钒衍生物增殖作用中起作用的唯一因素，因为有些化合物是增殖抑制剂。通过UMR106细胞中的碱性磷酸酶比活性和胶原蛋白合成来评估细胞分化。所有配合物均抑制碱性磷酸酶活性，其中半乳糖配合物最为有效（IC50 = 43微摩尔/升）。与海藻糖形成的配合物TreVO是刺激胶原蛋白合成（为基础水平的142%）和葡萄糖消耗（为基础水平的132%）最有效的试剂。一种胞质酪氨酸蛋白激酶和糖原合酶激酶-3似乎参与了钒衍生物对葡萄糖消耗的刺激作用。在该系列中，只有TreVO具备良好的胰岛素模拟物和成骨药物的特性。此外，该配合物是未转化成骨细胞增殖的良好促进剂，而对肿瘤成骨细胞有抑制作用。与葡萄糖形成的配合物GluVO对肿瘤细胞的毒性也比对未转化细胞的毒性更大。这2种钒衍生物是良好的潜在抗肿瘤药物。所有结果表明，钒化合物的生物学效应是一个复杂的现象，受络合作用、剂量、配体性质和细胞类型的影响。
