Open AccessPotent inhibition of in vivo angiogenesis and tumor growth by a novel cyclooxygenase‐2 inhibitor, enoic acanthoic acid
Author(s) -
Jung Hye Jin,
Shim Joong Sup,
Suh YoungGer,
Kim YoungMyeong,
Ono Mayumi,
Kwon Ho Jeong
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00617.x
Subject(s) - angiogenesis , cyclooxygenase , in vivo , chorioallantoic membrane , basic fibroblast growth factor , pharmacology , neovascularization , angiogenesis inhibitor , matrix metalloproteinase , vascular endothelial growth factor , cancer research , matrix metalloproteinase inhibitor , celecoxib , chemistry , biology , growth factor , biochemistry , enzyme , vegf receptors , receptor , microbiology and biotechnology
Recent studies have shown that cyclooxygenase‐2 is crucially involved in angiogenesis. In fact, several specific cyclooxygenase‐2 inhibitors suppress angiogenesis in vivo , suggesting that cyclooxygenase‐2 is a promising target for the treatment of angiogenesis‐related diseases. In the present study we investigate the activity of a new cyclooxygenase‐2 inhibitor, enoic acanthoic acid (EAA), which was synthesized from the known natural cyclooxygenase‐2 inhibitor, acanthoic acid (AA). The demonstration of a high correlation between EAA‐ and celecoxib‐induced gene expression signatures in microarray experiments validated the specificity of EAA on cyclooxygenase‐2. In angiogenesis assays, EAA potently inhibited basic fibroblast growth factor‐induced invasion and tube formation of bovine aortic endothelial cells in vitro . Moreover, this inhibitor prevented both neovascularization of the chorioallantoic membrane of growing chick embryo and basic fibroblast growth factor‐induced mouse corneal angiogenesis in vivo . EAA also significantly suppressed the growth of bladder tumors in a mouse model, showing better antitumor activity than celecoxib. Furthermore, gelatin zymogram analysis revealed that EAA potently inhibited the activities of matrix metalloproteinase 2 and 9. These results clearly demonstrate that EAA is a promising agent for the prevention and treatment of angiogenesis‐related diseases including cancer. ( Cancer Sci 2007; 98: 1943–1948)