期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 141, 期 -, 页码 17-27出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2014.08.006
关键词
Copper(II) complex; DNA binding; DNA cleavage; Anticancer; Apoptosis
资金
- 973 Program [2014CB845604]
- NSFC [21172273, 21171177, 91122010]
- Program for Changjiang Scholars and Innovative Research Team at the University of China [IRT1298]
- Research Fund for the Doctoral Program of Higher Education [20110171110013]
Three novel copper(II) complexes (CuLCl2)-Cl-1 (1) (L-1 = 4'-(3-methoxyphenyl)-2,2':6'-2 ''-terpyridine), (CuLCl2)-Cl-2 (2) (L-2 = 4'-(4-methoxyphenyl)-2,2':6'-2 ''-terpyridine) and (CuLCl2)-Cl-3 (3) (L-3 = 4'-(3,5-dimethoxyphenyl)-2,2':6'-2 ''-terpyridine) have been synthesized and characterized. Absorption spectral titration experiments, ethidium bromide displacement assays, and cyclic voltammetric experiments were carried out and the results suggested that these complexes bound to DNA through an intercalative mode. Moreover, these complexes were found to cleave pBR322 DNA efficiently in the presence of glutathione (GSH), and exhibited good anticancer activity against HeLa, Hep-G2 and BEL-7402 cell lines. Nuclear chromatin cleavage was also observed by acridine orange/ethidium bromide (AO/EB) staining assays and comet assays. These results demonstrated that these three Cu(II) complexes caused DNA damage and induced the apoptosis of HeLa cells. Mechanistic investigations revealed the participation of reactive oxygen species which can be trapped by reactive oxygen species (ROS) radical scavengers and ROS sensors. (C) 2014 Elsevier Inc. All rights reserved.
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