Chuan-Chuan Zeng

Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western blot analysis of ruthenium(II) polypyridyl complex against human lung decarcinoma A549 cell

A new ruthenium(II) polypyridyl complex [Ru(dmp)2(pddppn)](ClO4)2Ru1 was synthesized and characterized. The cytotoxic activity in vitro of the complex was evaluated by MTT method. Ru1 shows high effect on the inhibition of the cell growth against BEL-7402, HeLa, MG-63 and A549 cells with low IC50 values of 1.6±0.4, 9.0±0.8, 1.5±0.2 and 1.5±0.3 μM, respectively. The cellular uptake indicates that Ru1 can enter into the cytoplasm and accumulate in the cell nuclei. Ru1 can induce apoptosis in A549 cells and enhance the levels of reactive oxygen species (ROS) and induce the decrease of mitochondrial membrane potential. In addition, Ru1 can down-regulate the levels of Bcl-2, Bcl-x, Bak, and Bim expression and up-regulate the expression of Bag-1 and Bad. The complex induces apoptosis of A549 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulating the expression of caspases and Bcl-2 family proteins.

Apoptosis, autophagy, cell cycle arrest, cell invasion and BSA-binding studies in vitro of ruthenium(II) polypyridyl complexes

Ruthenium(II) polypyridyl complexes show high anticancer activity, and can induce apoptosis. Herein, a new ligand AQTP (AQTP = 12-acenaphtho[1,2-b]quinoxalin-9-yl-4,5,9,14-tetraazabenzo[b]triphenylene) and its four ruthenium(II) polypyridyl complexes [Ru(N-N)2(AQTP)](ClO4)2 (N-N = dmb: 4,4′-dimethyl-2,2′-bipyridine 1; bpy: 2,2′-bipyridine 2; phen: 1,10-phenanthroline 3 and dmp: 2,9-dimethyl-1,10-phenanthroline 4) were synthesized and characterized. The cytotoxic activity in vitro of the complexes against BEL-7402, A549, HeLa, HepG2, MG-63 and normal cell HLF was investigated using the MTT method (MTT = (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)). The apoptosis was assayed with AO/EB and Hoechst 33258 staining methods. The ROS, mitochondrial membrane potential and autophagy were studied using a fluorescent microscope. The expression of caspases and Bcl-2 family proteins was investigated by western blot analysis. The IC50 values of complexes 1–4 toward A549 cells are 5.0 ± 0.8, 10.0 ± 0.7, 45.0 ± 1.4 and 3.8 ± 0.1 μM. The complexes can increase the levels of reactive oxygen species (ROS), and induce a decrease in the mitochondrial membrane potential. Complexes 1–4 inhibit cell growth at the G0/G1 phase in A549 cells, and the complexes can induce both autophagy and apoptosis, and the complexes induce apoptosis through a ROS-mediated mitochondrial dysfunction pathway.

Effects of daidzein in regards to cytotoxicity in vitro, apoptosis, reactive oxygen species level, cell cycle arrest and the expression of caspase and Bcl-2 family proteins

In the present study, the in vitro cytotoxicity of daidzein was evaluated in human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. BEL-7402 cells were sensitive to daidzein treatment, with an IC50 value of 59.7±8.1 µM. Daidzein showed no cytotoxic activity toward A549, HeLa, HepG-2 and MG-63 cells. Daidzein increased the levels of reactive oxygen species (ROS) and induced a decrease in mitochondrial membrane potential. Morphological and comet assays showed that daidzein effectively induced apoptosis in BEL-7402 cells. Additionally, daidzein caused cell cycle arrest at the G2/M phase in the BEL-7402 cell line. Daidzein downregulated the expression of Bcl-2, Bcl-x and Baid proteins and upregulated the levels of Bim protein in the BEL-7402 cells. The results demonstrated that daidzein induced BEL-7402 cell apoptosis through an ROS-mediated mitochondrial dysfunction pathway.

Photoinduced ROS regulation of apoptosis and mechanism studies of iridium(III) complex against SGC-7901 cells

A new iridium(III) complex, [Ir(ppy)2(FBPIP)]PF6 (Ir-1), was synthesized and characterized. The cytotoxic activity of this complex against SGC-7901, PC-12, SiHa, HepG2, BEL-7402, A549, HeLa and normal LO2 cells was investigated using the MTT method. The complex showed no cytotoxic activity against the selected cell lines. However, upon irradiation, the complex displayed potent anti-proliferative activity toward SGC-7901 cells, with a low IC50 value of 6.1 ± 0.6 μM, and showed selectivity between cancer and normal cells. Apoptosis was assayed using the AO/EB staining method. The level of reactive oxygen species (ROS), mitochondrial membrane potential, autophagy and cell invasion were studied under a fluorescence microscope. The cell cycle distribution was studied by flow cytometry. The expression of caspase and Bcl-2 family proteins was investigated by western blot. Complex Ir-1 was shown to accumulate preferentially in the mitochondria of SGC-7901 cells and induced apoptosis via the mitochondrial pathway, which involved ROS generation, mitochondrial membrane potential depolarization, and Bcl-2 and caspase family member activation. These results demonstrate that the complex induces cancer cell apoptosis by acting on mitochondrial pathways.

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.