Bing-Jie Han

Cytotoxicity in vitro, cell migration and apoptotic mechanism studies induced by ruthenium(II) complexes

Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(DHBT)](ClO4)2 (1) (DHBT = 12,14-dihydroxyl-4,5,9,10,11,13-hexaazabenzo[b]triphenylene, dmb = 4,4′-dimethyl-2,2′-bipyridine), [Ru(bpy)2(DHBT)](ClO4)2 (2) (bpy = 2,2′-bipyridine), [Ru(phen)2(DHBT)](ClO4)2 (3) (phen = 1,10-phenanthroline) and [Ru(dmp)2(DHBT)](ClO4)2 (4) (dmp = 2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized. The cytotoxicity in vitro of these complexes was evaluated against human HepG-2, HeLa, A549, MG-63 and BEL-7402 cancer cell lines. The IC50 values of the complexes toward selected cell lines range from 14.9 ± 1.1 to 30.1 ± 2.7 μM. The cytotoxicity and the levels of reactive oxygen species were found to increase with increasing concentrations of the complexes. The complexes are sensitive to MG-63 cells and can inhibit the MG-63 cell migration. Morphological and comet assay studies show that the complexes can effectively induce apoptosis in MG-63 cells. Complex 2 inhibits the cell growth at the G0/G1 phase, whereas the other complexes exhibit the antiproliferative mechanism at the S phase in the MG-63 cell line. The complexes can downregulate the expression of Bcl-2 protein and upregulate the levels of Bad protein in MG-63 cells. The complexes induce MG-63 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway.

Studies on apoptosis in HeLa cells via the ROS-mediated mitochondrial pathway induced by new dibenzoxanthenes

Two positional isomers of dibenzoxanthenes C1 and C2 were synthesized and characterized. The crystal structures of the compounds were solved by single-crystal X-ray diffraction. Binding the two compounds with CT-DNA (calf thymus DNA)/BSA (bovine serum albumin) was thoroughly investigated by UV-Vis and fluorescence spectroscopy. The compounds interact with DNA through an intercalative mode and show strong affinities with BSA. Their cytotoxicity upon irradiation was investigated in vitro using the MTT method. By comparing the two isomers, C1 and C2, compound C2 showed greater enhanced therapeutic potential upon irradiation with visible light. Significant nuclear damage of HeLa cells was observed after a comet assay. These compounds inhibited cell growth in HeLa cells at the S phase. These compounds have been found to induce apoptosis in HeLa cells using AO/EB staining experiments and flow cytometry. The two compounds can enhance the intracellular reactive oxygen species and decrease the mitochondrial membrane potential. The compounds activated caspase-3, caspase-7, procaspase-7 and down-regulated the expression levels of the anti-apoptotic proteins Bcl-2 and Bcl-x, and up-regulated the expression levels of the pro-apoptotic proteins Bax and Bim. The compounds induced apoptosis of HeLa cells via a ROS-mediated mitochondrial dysfunction pathway.

DNA-Binding, Photocleavage, and Photodynamic Anti-cancer Activities of Pyridyl Corroles

The DNA-binding, photocleavage, and antitumor activity of three free base pyridyl corroles 1, 2, and 3 have been investigated. The binding affinity toward CT-DNA decreases with increasing number of pentafluorophenyl, whereas the photocleavage activity toward pBR322 DNA becomes more efficient. Singlet oxygen was demonstrated as active species responsible for DNA cleavage. These corroles exhibited high cytotoxicity against three tested cancer cells (Hela, HapG2, and A549) and the cytotoxicity could be further enhanced under irradiation. Intracellular reactive oxygen species level was also monitored using HeLa Cells upon the combined treatment of corroles and light. These corroles could be absorbed by HeLa cells at low concentration. They can induce the decrease of mitochondrial membrane potential and apoptosis of tumor cells under irradiation.

Platycodin D induced apoptosis and autophagy in PC-12 cells through mitochondrial dysfunction pathway.

In this article, the in vitro cytotoxicity of platycodin D was evaluated in human PC-12, SGC-7901, BEL-7402, HeLa and A549 cancer cell lines. PC-12 cells were sensitive to platycodin D treatment, with an IC50 value of 13.5±1.2μM. Morphological and comet assays showed that platycodin D effectively induced apoptosis in PC-12 cells. Platycodin D increased the levels of reactive oxygen species (ROS) and induced a decrease in mitochondrial membrane potential. Platycodin D induced cell cycle arrest at the G0/G1 phase in the PC-12 cell line. Platycodin D can induce autophagy. In addition, platycodin D can down-regulate the expression of Bcl-2 and Bcl-x, and up-regulate the levels of Bid protein in the PC-12 cells. The results demonstrated that platycodin D induced PC-12 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway.