title: The induction of apoptosis in SGC-7901 cells through the ROS-mediated mitochondrial dysfunction pathway by a Ir(III) complex.
abstract: A new ligand BTCP and its iridium(III) complex [Ir(ppy)2(BTCP)]PF6(Ir-1) were synthesized and characterized by elemental analysis, ESI-MS, IR,1H NMR and13C NMR. The cytotoxic activity in vitro of the ligand and its complex against SGC-7901, HeLa, HOS, PC-12, BEL-7402, MG-63, SiHa, A549, HepG2 and normal cell LO2 were evaluated by 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 reactive oxygen species (ROS), mitochondrial membrane potential, autophagy and cell invasion were studied under fluorescent microscope. The expression of caspases and Bcl-2 family proteins were investigated by western blot. The IC50values of complex toward SGC-7901, BEL-7402 and MG-63 cells are 3.9 ± 0.5, 5.4 ± 1.2 and 4.2 ± 0.6 µM. The complex can increase the levels of ROS, and induce a decrease in the mitochondrial membrane potential. Ir-1 inhibits the cell growth at G0/G1 phase in SGC-7901 cells, and the complex can induce both autophagy and apoptosis and inhibit the cell invasion. And the complex induces apoptosis through a ROS-mediated mitochondrial dysfunction pathway.
authors: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors: Cheng
authors: C
authors: Zhang
authors: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors: Shang-Hai
authors: SH
authors: Lai
authors: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors: Chuan-Chuan
authors: CC
authors: Zeng
authors: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors: Bing
authors: B
authors: Tang
authors: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors: Dan
authors: D
authors: Wan
authors: School of Basic Science, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China. degangxing@126.com.
authors: De-Gang
authors: DG
authors: Xing
authors: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China. lyjche@163.com.|Guangdong Cosmetics Engineering and Technology Research Center, Guangzhou, 510006, People's Republic of China. lyjche@163.com.
authors: Yun-Jun
authors: YJ
authors: Liu
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D007495:Iridium; D020169:Caspases
keywords: Apoptosis; Autophagy; Bcl-2 family proteins; Cell invasion; Ir(III) complex