Wang Chuan, Yu Qianqian, Yang Licong, Liu Yanyu, Sun Dongdong, Huang Yongchao, Zhou Yanhui, Zhang Qianling, Liu Jie
Department of Chemistry, Jinan University, Guangzhou 510632, People's Republic of China.
Biometals. 2013 Jun;26(3):387-402. doi: 10.1007/s10534-013-9622-6. Epub 2013 Mar 30.
In the present study, the interaction between GC-rich sequence of bcl-2 gene P1 promoter (Pu39) and two ruthenium (II) polypyridyl complexes, [Ru(bpy)₂(tip)]²⁺ (1) and [Ru(phen)₂(tip)]²⁺ (2), was investigated by UV-Visible, fluorescence spectroscopy, circular dichroism, fluorescence resonance energy transfer melting assay and polymerase chain reaction stop assay. Those experimental results indicated that the two complexes can effectively stabilize the G-quadruplex of Pu39. It was found that the complex 2 exhibited greater cytotoxic activity than 1 against human Hela cells and can enter into Hela cells in a short period of time to effectively induce apoptosis of cells. Further experiments found that complexes 1 and 2 had as potent inhibitory effects on ECV-304 cell migration as suramin. Those noteworthy results provide new insights into the development of anticancer agents for targeting G-quadruplex DNA.
在本研究中，通过紫外可见光谱、荧光光谱、圆二色光谱、荧光共振能量转移熔解分析和聚合酶链反应终止分析，研究了bcl-2基因P1启动子富含GC的序列（Pu39）与两种钌（II）多吡啶配合物[Ru(bpy)₂(tip)]²⁺（1）和[Ru(phen)₂(tip)]²⁺（2）之间的相互作用。这些实验结果表明，这两种配合物能够有效地稳定Pu39的G-四链体。研究发现，配合物2对人Hela细胞表现出比配合物1更强的细胞毒性活性，并且能够在短时间内进入Hela细胞以有效诱导细胞凋亡。进一步的实验发现，配合物1和2对ECV-304细胞迁移具有与苏拉明同样有效的抑制作用。这些值得关注的结果为开发靶向G-四链体DNA的抗癌药物提供了新的见解。
