Wondonin, a novel compound, inhibits hypoxia-induced angiogenesis through hypoxia-inducible factor 1 alpha.
Hypoxia regulates a variety of transcription factors including HIF-1, which has been considered a target for anti-angiogenic therapy. While searching for a novel anti-angiogenic agent that would inhibit HIF-1 activity, we identified wondonin, a new bis imidazole purified from an association of the sponges Poecillastra wondoensis. Wondonin significantly decreased hypoxia-induced HIF-1alpha protein and VEGF expression and inhibited angiogenesis in vitro and in vivo. Furthermore, wondonin down-regulated HIF-1alpha protein through the increased interaction with the pVHL in immortalized human keratinocyte cell line. Wondonin also decreased the immunoreactivities of CD31 and VEGF in epidermal hyperplasia in mice. Taken together, these results suggested that wondonin had the potential to become the anti-angiogenic therapeutic agent to target HIF-1alpha.
Jun
Hyoung-Oh
HO
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Kim
Younghwa
Y
Kwon
Yoo-Wook
YW
Hong
Soon-Sun
SS
Kim
Kyu-Won
KW
Shin
Jongheon
J
Kim
Tae-Yoon
TY
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D002642:Chick Embryo; D015536:Down-Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007093:Imidazoles; D013463:Sulfuric Acid Esters; D042461:Vascular Endothelial Growth Factor A; C525354:wondonin