title: DMPPQA, a novel angiogenesis inhibitor, induces apoptosis in human colon cancer HCT-116 cells and HUVECs.
abstract: Cytotoxic activity of 5,7-dimethoxy-2-phenyl-N-propylquinolin-4-amine (DMPPQA) was investigated in human colon cancer cells HCT-116 and umbilical vein endothelial cell line HUVEC. The IC(50) of DMPPQA on HCT-116 and HUVEC cells were respectively 1.26 and 7.43 µM after 72 h treatment. DMPPQA inhibited the growth of HCT-116 and HUVEC cells in concentration- and time-dependent manners. Typical morphological changes of apoptotic body formation were seen after DMPPQA with Hoechst 33258 staining. FCM analysis showed that DMPPQA induced apoptosis, mitochondrial membrane potential loss (ΔΨm) and increase in the production of intracellular reactive oxygen species (ROS) of HCT-116 cells. After treating with DMPPQA, apoptosis-related protein expression of Bax, cytochrome c, caspase-9, caspase-3, PARP-1 and P53 increased and Bcl-2 protein expression decreased. DMPPQA treatment of HUVECs reduced cell migration and microcapillary tube formation in a Matrigel matrix. It also decreased VEGF protein expression. Thus DMPPQA acts as an angiogenesis inhibitor and induces cell apoptosis by a caspase-dependent mitochondrial pathway.
authors.affiliation: School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, Jiangsu, 213164, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.forename: Hefei
authors.initials: H
authors.lastname: Jiang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Wenqun
authors.initials: W
authors.lastname: Xin
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Hu
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C000592352:5,7-dimethoxy-2-phenyl-N-propylquinolin-4-amine; D000634:Aminoquinolines; D020533:Angiogenesis Inhibitors; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases
keywords: DMPPQA; ROS; angiogenesis inhibitor; apoptosis; mitochondria