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DMPPQA , a novel angiogenesis inhibitor, induces apoptosis in human colon cancer HCT ‐116 cells and HUVEC s
Author(s) -
Ren Jie,
Jiang Hefei,
Zhao Juan,
Xin Wenqun,
Xu Yuanyuan,
Chen Xin,
Hu Kun
Publication year - 2014
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10209
Subject(s) - apoptosis , matrigel , cytochrome c , umbilical vein , angiogenesis , human umbilical vein endothelial cell , microbiology and biotechnology , chemistry , cancer cell , cell culture , biology , cancer research , biochemistry , cancer , in vitro , genetics
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 (ΔΨ m ) 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.