α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression.
Biochem Biophys Res Commun
; 521(4): 947-951, 2020 01 22.
Article
em En
| MEDLINE
| ID: mdl-31718795
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores da Angiogênese
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Alfa-Tocoferol
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Angiopoietina-2
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Neovascularização Patológica
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article