Cytotoxicity, DNA binding and cell apoptosis induction of a zinc(II) complex of HBrQ

A new zinc(II) complex (1) of 5-bromo-8-hydroxyquinoline (HBrQ) was prepared and structurally characterized using IR, ESI-MS, elemental analysis, 1H and 13C NMR, as well as single crystal X-ray diffraction analysis. The DNA binding study on complex 1, which was performed using UV-vis, fluorescence and circular dichroism (CD) spectral analyses, suggested that complex 1 interacts with ct-DNA mainly via an intercalative binding mode. The in vitro cytotoxicity of complex 1, compared with Zn(OAc)2·H2O, HBrQ and cisplatin, was screened against a series of tumor cell lines as well as the normal liver cell line HL-7702 using the MTT assay. Complex 1 showed much higher cytotoxicity than Zn(OAc)2·H2O and HBrQ against most of the tumor cell lines, in which BEL-7404 was the most sensitive tumor cell line towards 1, with an IC50 value of 8.69 ± 0.04 μM. Complex 1 was found to greatly induce cell cycle arrest in the BEL-7404 cells at the G2 phase, and consequently to induce cell apoptosis in a dose-dependent mode, which is suggested by the cell apoptosis analysis via the Hoechst 33258 and AO/EB staining assays. Targeting the mitochondria pathway due to the redox activity of Zn, the apoptotic mechanism in the BEL-7404 cells treated by 1 was investigated using reactive oxygen species (ROS) detection, intracellular calcium concentration measurement and caspase-9/3 activity assay, which showed that the cell apoptosis induced by 1 was closely related to the loss of mitochondrial membrane potential, ROS production and enhancement of intracellular [Ca2+], which trigger caspase-9/3 activation via the mitochondrial dysfunction pathway.