title: 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation.
abstract: Reactive oxygen species (ROS) are involved in the signaling pathway and are triggered by angiogenic factors, including vascular endothelial growth factor and angiopoietins. 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl (4-ISO-Tempo) is one of the nitroxides that exhibits antioxidant activity. However, the anti-angiogenic effect of 4-ISO-Tempo remains unknown. The aim of this study was to investigate the effect of 4-ISO-Tempo on tumor proliferation and angiogenesis as well as its underlying mechanisms. Our results revealed that 4-ISO-Tempo significantly inhibited the viability of neoplastic and endothelial cells. Furthermore, the effective concentration of 4-ISO-Tempo on human microvascular endothelial cell 1 (HMEC-1) was lower than that on human lung adenocarcinoma A549 and human colon cancer SW620 cells. This suggested that endothelial cells were more sensitive to 4-ISO-Tempo than tumor cells. Furthermore, we demonstrated that 4-ISO-Tempo also suppressed secretion of matrix metalloproteinase (MMP)-2 and MMP-9, and migration and tube formation of HMEC-1 cells. The mechanism is attributed to the decreasing ROS generation and further phosphorylation of vascular endothelial growth factor receptor 2 and Tie2. Our findings suggest that 4-ISO-Tempo should be investigated for its usefulness in anti-angiogenesis therapies.
authors.affiliation: College of Basic Medicine, Key Laboratory of Preclinical Study for New Drugs of Gansu, Lanzhou University, Lanzhou, Gansu 730000, P.R. China; Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Clinical Laboratory, Affiliated Hospital of Medical College of Northwest University for Nationalities, Lanzhou, Gansu 730030, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Clinical Laboratory, Affiliated Hospital of Medical College of Northwest University for Nationalities, Lanzhou, Gansu 730030, P.R. China.
authors.forename: Shuangsheng
authors.initials: S
authors.lastname: Huang
authors.affiliation: College of Basic Medicine, Key Laboratory of Preclinical Study for New Drugs of Gansu, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Lamei
authors.initials: L
authors.lastname: Hu
authors.affiliation: College of Basic Medicine, Key Laboratory of Preclinical Study for New Drugs of Gansu, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
authors.forename: Zheyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Basic Medicine, Key Laboratory of Preclinical Study for New Drugs of Gansu, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Basic Medicine, Key Laboratory of Preclinical Study for New Drugs of Gansu, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Li
keywords: 2; 4-isothiocyanate-2; 6; 6-tetramethyl piperidinooxyl; Tie2; angiogenesis; reactive oxygen species; vascular endothelial growth factor receptor 2