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.
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2011 Jan 7|
Bibliographical noteFunding Information:
This study was partly supported by grants from the National Research Foundation of Korea funded by the Korean Government (MEST; 2009-0092964 and 2010-0017984), the Translational Research Center for Protein Function Control, KRF (2009-0083522), the National R&D Program for Cancer Control (0620350), the Ministry of Health & Welfare, and the Brain Korea 21 Project, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology