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Identification and biological activities of a new antiangiogenic small molecule that suppresses mitochondrial reactive oxygen species.

Abstract：

:Mitochondrial reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. In particular, high levels of mitochondrial ROS in hypoxic cells regulate many angiogenesis-related diseases, including cancer and ischemic disorders. Here we report a new angiogenesis inhibitor, YCG063, which suppressed mitochondrial ROS generation in a phenotypic cell-based screening of a small molecule-focused library with an ArrayScan HCS reader. YCG063 suppressed mitochondrial ROS generation under a hypoxic condition in a dose-dependent manner, leading to the inhibition of in vitro angiogenic tube formation and chemoinvasion as well as in vivo angiogenesis of the chorioallantoic membrane (CAM) at non-toxic doses. In addition, YCG063 decreased the expression levels of HIF-1α and its target gene, VEGF. Collectively, a new antiangiogenic small molecule that suppresses mitochondrial ROS was identified. This new small molecule tool will provide a basis for a better understanding of angiogenesis driven under hypoxic conditions.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kim KH,Park JY,Jung HJ,Kwon HJ

doi

10.1016/j.bbrc.2010.12.022

subject

Has Abstract

pub_date

2011-01-07 00:00:00

pages

541-5

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(10)02247-3

journal_volume

404

pub_type

杂志文章

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