4‑isothiocyanate‑2, 2, 6, 6‑tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation

  • Authors:
    • Yuanyuan Liu
    • Jing Gao
    • Shuangsheng Huang
    • Lamei Hu
    • Zhiqiang Wang
    • Zheyuan Wang
    • Xiao Chen
    • Xiaoyu Zhang
    • Wenguang Li
  • View Affiliations

  • Published online on: August 3, 2016     https://doi.org/10.3892/ol.2016.4948
  • Pages: 2828-2834
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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.
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October-2016
Volume 12 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Liu Y, Gao J, Huang S, Hu L, Wang Z, Wang Z, Chen X, Zhang X and Li W: 4‑isothiocyanate‑2, 2, 6, 6‑tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation. Oncol Lett 12: 2828-2834, 2016
APA
Liu, Y., Gao, J., Huang, S., Hu, L., Wang, Z., Wang, Z. ... Li, W. (2016). 4‑isothiocyanate‑2, 2, 6, 6‑tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation. Oncology Letters, 12, 2828-2834. https://doi.org/10.3892/ol.2016.4948
MLA
Liu, Y., Gao, J., Huang, S., Hu, L., Wang, Z., Wang, Z., Chen, X., Zhang, X., Li, W."4‑isothiocyanate‑2, 2, 6, 6‑tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation". Oncology Letters 12.4 (2016): 2828-2834.
Chicago
Liu, Y., Gao, J., Huang, S., Hu, L., Wang, Z., Wang, Z., Chen, X., Zhang, X., Li, W."4‑isothiocyanate‑2, 2, 6, 6‑tetramethyl piperidinooxyl inhibits angiogenesis by suppressing VEGFR2 and Tie2 phosphorylation". Oncology Letters 12, no. 4 (2016): 2828-2834. https://doi.org/10.3892/ol.2016.4948