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2-Methoxycinnamaldehyde Inhibits Tumor Angiogenesis by Suppressing Tie2 Activation

2-Methoxycinnamaldehyde Inhibits Tumor Angiogenesis by Suppressing Tie2 Activation

Daishi Yamakawa, Hiroyasu Kidoya, Susumu Sakimoto, Weizhen Jia, Nobuyuki Takakura

Biochem Biophys Res Commun. 2011 Nov 11;415(1):174-80.

PMID: 22033407

Abstract:

Blood vessels are mainly composed of intraluminal endothelial cells (ECs) and mural cells adhering to the ECs on their basal side. Immature blood vessels lacking mural cells are leaky; thus, the process of mural cell adhesion to ECs is indispensable for stability of the vessels during physiological angiogenesis. However, in the tumor microenvironment, although some blood vessels are well-matured, the majority is immature. Because mural cell adhesion to ECs also has a marked anti-apoptotic effect, angiogenesis inhibitors that destroy immature blood vessels may not affect mature vessels showing more resistance to apoptosis. Activation of Tie2 receptor tyrosine kinase expressed in ECs mediates pro-angiogenic effects via the induction of EC migration but also facilitates vessel maturation via the promotion of cell adhesion between mural cells and ECs. Therefore, inhibition of Tie2 has the advantage of completely inhibiting angiogenesis. Here, we isolated a novel small molecule Tie2 kinase inhibitor, identified as 2-methoxycinnamaldehyde (2-MCA). We found that 2-MCA inhibits both sprouting angiogenesis and maturation of blood vessels, resulting in inhibition of tumor growth. Our results suggest a potent clinical benefit of disrupting these two using Tie2 inhibitors.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1504741	2-Methoxycinnamaldehyde		1504-74-1	Price

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