A benzoxazine derivative induces vascular endothelial cell apoptosis in the presence of fibroblast growth factor-2 by elevating NADPH oxidase activity and reactive oxygen species levels.
Previously, we found that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (DBO) promoted apoptosis of human umbilical vascular endothelial cells (HUVECs) deprived of growth factors. In this study, we aimed to investigate the effect of DBO and its mechanism of action on angiogenesis and apoptosis of HUVECs in the presence of fibroblast growth factor-2 (FGF-2), which promotes angiogenesis and inhibits apoptosis in vivo and in vitro. DBO significantly inhibited capillary-like tube formation by promoting apoptosis of HUVECs in the presence of FGF-2 in vitro. Furthermore, DBO elevated the levels of reactive oxygen species (ROS) and nitric oxide (NO) and increased the activity of NADPH oxidase and inducible nitric oxide synthase (iNOS) in promoting apoptosis under this condition. Moreover, when NADPH oxidase was inhibited by its specific inhibitor, dibenziodolium chloride (DPI), DBO could not elevate ROS and NO levels in HUVECs. The data suggest that DBO is a new modulator of apoptosis in vitro, and it might function by increasing the activity of NADPH oxidase and iNOS, subsequently elevating the levels of ROS and NO in HUVECs. The findings of this study provide a new small molecule for investigating the FGF-2/NADPH oxidase/iNOS signaling pathway in apoptosis.
Zhao
Jing
J
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
He
Qiuxia
Q
Cheng
Yizhe
Y
Zhao
Baoxiang
B
Zhang
Yun
Y
Zhang
Shangli
S
Miao
Junying
J
D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C545140:6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine; D010078:Oxazines; D017382:Reactive Oxygen Species; D016222:Fibroblast Growth Factor 2; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases