
Inhibition of Angiogenesis by Rhizoxin, a Microbial Metabolite Containing Two Epoxide Groups
Author(s) -
Onozawa Chizuko,
Shimamura Mariko,
Iwasaki Shigeo,
Oikawa Tsutomu
Publication year - 1997
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1997.tb00339.x
Subject(s) - angiogenesis , metabolite , chorioallantoic membrane , in vivo , angiogenesis inhibitor , neovascularization , pharmacology , biochemistry , chemistry , epoxide , biology , cancer research , genetics , catalysis
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 ID S(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.