Inhibition of Angiogenesis by Rhizoxin, a Microbial Metabolite Containing Two Epoxide Groups |
| |
| Authors: | Chizuko Onozawa Mariko Shimamura Shigeo Iwasaki Tsutomu Oikawa |
| |
| Affiliation: | Department of Cancer Therapeutics, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), 3–18-22 Honkomagome, Bunkyo-ku, Tokyo 113;Institute of Molecular and Cellular Biosdences, University of Tokyo, 1–1-1 Yayoi, Bunkyo-ku, Tokyo 113 |
| |
| Abstract: | Previous studies by our and other groups have shown that microbial products containing more than one epoxide group, including eponemycin, radicicol, depudecin and AGM-1470, exhibit anti-angio-genic activity in an in vivo assay system involving chorioallantoic membranes (CAMs) of growing chick embryos. Based on these findings, rhizoxin, a microbial metabolite that contains two epoxide groups and exhibits anti-tubulin activity, was tested for anti-angiogenic activity in a CAM assay system. Rhizoxin caused dose-dependent inhibition of embryonic angiogenesis, the IDS(1 value being 2 ng (3.2 pmol) per egg. In addition, this compound (2 nig/kg i.p.) significantly suppressed neovascnlarizatlou induced by M5076 mouse tumor cells in a mouse dorsal air sac assay system, compared to the vehicle alone (P<0.05). These results indicate that rhizoxin is a novel inhibitor of angiogenesis, and that it has potential as a new therapeutic agent for cancer. |
| |
| Keywords: | Angiogenesis Angiogenesis inhibitor-Rhizoxin Epoxide group Angiostatic therapy |
|
|
