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DMPPQA, a novel angiogenesis inhibitor, induces apoptosis in human colon cancer HCT‐116 cells and HUVECs

Identifieur interne : 001073 ( Main/Exploration ); précédent : 001072; suivant : 001074

DMPPQA, a novel angiogenesis inhibitor, induces apoptosis in human colon cancer HCT‐116 cells and HUVECs

Auteurs : Jie Ren ; Hefei Jiang ; Juan Zhao ; Wenqun Xin ; Yuanyuan Xu ; Xin Chen ; Kun Hu

Source :

RBID : ISTEX:8E8899FCB0D7AFCF310D3D1AC8CD4C12302F5117

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 IC50 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.

Url:
DOI: 10.1002/cbin.10209


Affiliations:


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<div type="abstract" xml:lang="en">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 IC50 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.</div>
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