Aydın Ali, Korkmaz Sengul Aslan, Demir Veysel, Tekin Saban
Department of Molecular Biology and Genetics, Faculty of Science, Gaziosmanpaşa University, P.O. Box: 60240, Tokat, Turkey.
Department of Bioengineering, Faculty of Engineering, Tunceli University, Tunceli, Turkey.
Anticancer Agents Med Chem. 2017;17(6):865-874. doi: 10.2174/1871520617666170103102417.
In cancer, apoptosis relevant proteins-such as CaM kinase, Bcl-2 or P53, topoisomerase I, cell migration feature and DNA/BSA-macromolecules represent significant targets for current chemotherapeutics.
We recently reported two coordination compounds-[Cu(C6H16N2O2)2][Ni(CN)4] (1) and [Cu(C6H16 N2O2)Pd(CN)4] (2)-together with their IR spectra, magnetic properties, thermal analyses and crystal structures. Herein, we describe the ability of these complexes to induce apoptosis in relevant proteins and stimulate topoisomerase I activity, cell migration velocity and DNA/BSA binding properties.
The in vitro antiproliferative effects and cell toxicity of both compounds were investigated through pharmacological measurement techniques, and interactions between both compounds and CT-DNA/BSA were studied with UV-Vis spectroscopy and fluorescence spectroscopy. Results & Conclusion: Studies on cells revealed that 2 (i) demonstrated a high antiproliferative effect, which was higher toward HeLa and C6 cancer cells than toward healthy Vero cells; (ii) impaired the migration of HeLa cells; (iii) altered the P53-Bcl-2 ratio in favor of apoptosis; (iv) strongly bound to DNA/BSA macromolecules; and (v) inhibited human topoisomerase I and KpnI or BamHI restriction endonucleases. In conclusion, this preliminary information demonstrates that 2 may represent a promising antiproliferative agent and a potential candidate for a therapeutic approach against HeLa.
在癌症中,凋亡相关蛋白(如钙调蛋白激酶、Bcl-2或P53、拓扑异构酶I)、细胞迁移特性以及DNA/牛血清白蛋白大分子是当前化疗药物的重要靶点。
我们最近报道了两种配位化合物——[Cu(C6H16N2O2)2][Ni(CN)4](1)和[Cu(C6H16N2O2)Pd(CN)4](2)——及其红外光谱、磁性、热分析和晶体结构。在此,我们描述了这些配合物诱导相关蛋白凋亡以及刺激拓扑异构酶I活性、细胞迁移速度和DNA/牛血清白蛋白结合特性的能力。
通过药理学测量技术研究了这两种化合物的体外抗增殖作用和细胞毒性,并用紫外可见光谱和荧光光谱研究了这两种化合物与CT-DNA/牛血清白蛋白之间的相互作用。结果与结论:细胞研究表明,化合物2(i)表现出较高的抗增殖作用,对HeLa和C6癌细胞的作用比对健康的Vero细胞更强;(ii)损害HeLa细胞的迁移;(iii)改变P53-Bcl-2比值以促进凋亡;(iv)与DNA/牛血清白蛋白大分子强烈结合;(v)抑制人拓扑异构酶I以及KpnI或BamHI限制性内切酶。总之,这些初步信息表明化合物2可能是一种有前景的抗增殖剂,也是治疗HeLa的潜在候选药物。