Embellistatin, a microtubule polymerization inhibitor, inhibits angiogenesis both in vitro and in vivo.
The efficient inhibition of angiogenesis is considered as a promising strategy for the treatment of angiogenesis-related diseases including cancer. Herein, we report that embellistatin, a bicyclic ketone compound known as a microtubule polymerization inhibitor, exhibits anti-angiogenic activity. Embellistatin inhibited in vitro angiogenesis of bovine aortic endothelial cells (BAECs) such as bFGF-induced invasion and tube formation as well as bFGF-induced mouse corneal angiogenesis in vivo. Notably, embellistatin exhibited stronger inhibition activity for the growth of BAECs than that of normal and cancer cell lines. Cell cycle analysis revealed that the compound arrests cell cycle at G2/M phase, which is associated with the increased expression of p21(WAF1) and p53 partly. These results demonstrate that embellistatin may serve the basis for the development of new anti-angiogenic agents.
Jung
Hye Jin
HJ
Chemical Genomics Laboratory, Department of Biotechnology, College of Engineering, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Shim
Joong Sup
JS
Lee
Hyang Burm
HB
Kim
Chang-Jin
CJ
Kuwano
Takashi
T
Ono
Mayumi
M
Kwon
Ho Jeong
HJ
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000187:drug effects*; D009281:Naphthalenes / Q000008:administration & dosage*; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D006538:Heptanoic Acids; D009281:Naphthalenes; C517529:embellistatin