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ID 114071
Author
Hama, Susumu Kyoto Pharmaceutical University
Okamura, Yuriko Kyoto Pharmaceutical University
Kamei, Kazuho Kyoto Pharmaceutical University
Nagao, Saki Kyoto Pharmaceutical University
Hayashi, Mari Kyoto Pharmaceutical University
Maeda, Shizuka Kyoto Pharmaceutical University
Keywords
Tocopheryl succinate
Angiogenesis
Angiopoietin
Vascular stabilization
Content Type
Journal Article
Description
α-Tocopheryl succinate (TS) is a tocopherol derivative and has multifaceted anti-cancer effects; TS not only causes cancer cell-specific apoptosis but also inhibits tumor angiogenesis. Although TS has the potential to be used as a well-tolerated anti-angiogenic drug, it is still unclear which step of the angiogenic process is inhibited by TS. Here, we show that TS inhibits the expression of angiopoietin (Ang)-2, which induces destabilization of vascular structure in the initial steps of the angiogenic process. In mouse melanoma cells, TS treatment decreased mRNA and extracellular protein levels of Ang-2; however, the mRNA level of Ang-1, which stabilizes the vascular structure, remained unchanged. Furthermore, aorta ring and Matrigel plug angiogenesis assays indicated that the conditioned medium from TS-treated cells (CM-TS) inhibited neovascularization and blood leakage from the existing blood vessels, respectively. Following immunohistochemical staining of the vessels treated with CM-TS, imaging studies showed that the vascular endothelial cells were highly packed with pericytes. In conclusion, we found that TS inhibits Ang-2 expression and, consequently, stabilizes the vascular structure during the initial step of tumor angiogenesis.
Journal Title
Biochemical and Biophysical Research Communications
ISSN
0006291X
NCID
AA00564395
AA11542044
Publisher
Elsevier
Volume
521
Issue
4
Start Page
947
End Page
951
Published Date
2019-11-11
Rights
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Pharmaceutical Sciences