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Amino Acids. 2018 Aug;50(8):1121-1129. doi: 10.1007/s00726-018-2589-4. Epub 2018 May 23.

A fusion antitumor peptide regulates proliferation and apoptosis of endothelial cells.

Author information

1
School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
2
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
3
School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. minwang@cpu.edu.cn.
4
School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. qiuzheng@cpu.edu.cn.

Abstract

The present research has been carried out to elicit the mechanism of antiangiogenic activity of a fusion peptide P2. Peptide P2 was designed by the connection of a heptapeptide MMP inhibitor to ES-2, a fragment of Endostatin. In a previous study, P2 demonstrated strong antiangiogenic and antitumor effect, and the current work explains the antiangiogenic mechanism of P2 through endothelial cell proliferation and apoptosis. In our study, it was shown that P2 inhibited HUVECs proliferation at a low serum concentration and this effect might be achieved through arresting cell cycle by decreasing the expression level of Cyclin D1. In addition, P2 was found to induce apoptosis of HUVECs. Using Western blot, it was indicated that P2 induced the cleavage of Caspase-3, the hallmark protease of apoptosis. The activation and expression of the upstream regulator Caspase-9 can also be affected by P2 treatment. Furthermore, P2 reduced the protein level of antiangiogenic factors Bcl-xL and Bcl-2. These results revealed that P2 regulates endothelial cell apoptosis through intrinsic apoptotic pathway.

KEYWORDS:

Antiangiogenic mechanism; Endothelial apoptosis; Endothelial cell proliferation; Fusion peptide

PMID:
29796930
DOI:
10.1007/s00726-018-2589-4
[Indexed for MEDLINE]

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