Rozzo Carla, Sanna Daniele, Garribba Eugenio, Serra Maria, Cantara Alessio, Palmieri Giuseppe, Pisano Marina
Istituto CNR di Chimica Biomolecolare, Trav. La Crucca 3, I-07100 Sassari, Italy.
Dipartimento di Chimica e Farmacia, Università di Sassari, Via Vienna 2, I-07100 Sassari, Italy.
J Inorg Biochem. 2017 Sep;174:14-24. doi: 10.1016/j.jinorgbio.2017.05.010. Epub 2017 May 22.
In this study we evaluated the anticancer activity against malignant melanoma (MM) of four different vanadium species: the inorganic anion vanadate(V) (indicated with VN), and three oxidovanadium(IV) complexes, [VO(dhp)] where dhp is the anion 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS2), [VO(mpp)] where mpp is 1-methyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS3), and [VO(ppp)] where ppp is 1-phenyl-2-methyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS4). The antitumor effects of these compounds were studied against two different MM cell lines (A375 and CN-mel) and a fibroblast cell line (BJ) as normal control. All tested V compounds exert antiproliferative activity on MM cells in a dose dependent manner (IC ranges from 2.4μM up to 14μM) being A375 the most sensitive cell line. VN and VS2 were the two most active compounds against A375 (IC of 4.7 and 2.6μM, respectively), causing apoptosis and cell cycle block. The experimental data indicate that the cell cycle arrest occurs at different phases for the two V species analyzed (G2 checkpoint for VN and G0/G1 for VS2), showing the importance of the chemical form in determining their mechanism of action. These results add more insights into the landscape of vanadium versatility in biological systems and into its role as a potential cancer therapeutic agent.
在本研究中,我们评估了四种不同钒化合物对恶性黑色素瘤(MM)的抗癌活性:无机阴离子钒酸盐(V)(用VN表示),以及三种氧化钒(IV)配合物,[VO(dhp)],其中dhp是阴离子1,2 - 二甲基 - 3 - 羟基 - 4(1H)-吡啶酮(用VS2表示),[VO(mpp)],其中mpp是1 - 甲基 - 3 - 羟基 - 4(1H)-吡啶酮(用VS3表示),以及[VO(ppp)],其中ppp是1 - 苯基 - 2 - 甲基 - 3 - 羟基 - 4(1H)-吡啶酮(用VS4表示)。研究了这些化合物对两种不同的MM细胞系(A375和CN - mel)以及作为正常对照的成纤维细胞系(BJ)的抗肿瘤作用。所有测试的钒化合物均以剂量依赖性方式对MM细胞发挥抗增殖活性(IC范围为2.4μM至14μM),其中A375是最敏感的细胞系。VN和VS2是对A375活性最高的两种化合物(IC分别为4.7和2.6μM),可导致细胞凋亡和细胞周期阻滞。实验数据表明,对于所分析的两种钒化合物,细胞周期阻滞发生在不同阶段(VN为G2期检查点,VS2为G0/G1期),这表明化学形式在确定其作用机制方面的重要性。这些结果为钒在生物系统中的多功能性及其作为潜在癌症治疗剂的作用提供了更多见解。