Related Experiment Video
Updated: Jan 4, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
α-Tocopheryl succinate stabilizes the structure of tumor vessels by inhibiting angiopoietin-2 expression
Susumu Hama1, Yuriko Okamura1, Kazuho Kamei1
1Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan.
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.
Insights
α-Tocopheryl succinate (TS) inhibits tumor angiogenesis by reducing angiopoietin-2 (Ang-2) expression. This action stabilizes newly forming blood vessels, offering potential for well-tolerated anti-cancer therapy.
Area of Science:
- Oncology
- Vascular Biology
- Biochemistry
Background:
- α-Tocopheryl succinate (TS) exhibits anti-cancer properties, including apoptosis induction and anti-angiogenesis.
- The precise mechanism by which TS inhibits tumor angiogenesis remains unclear.
- Understanding TS's molecular targets is crucial for its therapeutic development.
Purpose of the Study:
- To elucidate the specific step in the angiogenic process targeted by TS.
- To investigate the effect of TS on angiopoietin (Ang)-1 and Ang-2 expression.
- To evaluate the anti-angiogenic potential of TS in preclinical models.
Main Methods:
- TS treatment of mouse melanoma cells.
- Quantitative analysis of Ang-1 and Ang-2 mRNA and protein levels.
- Aorta ring and Matrigel plug assays.
- Immunohistochemical staining and imaging of vascular structures.
Main Results:
- TS treatment significantly decreased both mRNA and extracellular protein levels of Ang-2.
- Ang-1 expression levels remained unaffected by TS treatment.
- Conditioned medium from TS-treated cells inhibited neovascularization and vascular leakage, stabilizing vessels with pericytes.
Conclusions:
- TS inhibits tumor angiogenesis by suppressing Ang-2 expression.
- This suppression stabilizes vascular structures in the early stages of angiogenesis.
- TS demonstrates potential as a well-tolerated anti-angiogenic agent for cancer treatment.
More Related Videos
08:52Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice
Published on: January 19, 2018
12:09A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics
Published on: June 16, 2013
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:15Drugs that Stabilize Microtubules
01:10Mechanism of Angiogenesis
01:10Drugs that Destabilize Microtubules
01:27Tumor Immunotherapy
02:17The Tumor Microenvironment