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

Ki Hyun Kim; Ju Yeol Park; Hye Jin Jung; Ho Jeong Kwon

doi:10.1016/j.bbrc.2010.12.022

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

Ki Hyun Kim, Ju Yeol Park, Hye Jin Jung, Ho Jeong Kwon

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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.

Original language	English
Pages (from-to)	541-545
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	404
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2010.12.022
Publication status	Published - 2011 Jan 7

Bibliographical note

Funding 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

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2010.12.022

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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.",

author = "Kim, {Ki Hyun} and Park, {Ju Yeol} and Jung, {Hye Jin} and Kwon, {Ho Jeong}",

note = "Funding 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.",

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AU - Kwon, Ho Jeong

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N2 - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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