title: Effect of 15-deoxyspergualin, a microbial angiogenesis inhibitor, on the biological activities of bovine vascular endothelial cells.
abstract: We found recently that 15-deoxyspergualin, an analog of spergualin, which is an antibiotic and includes a spermidine moiety in its structure, exhibits anti-angiogenic activity. We have now carried out in vitro experiments with bovine vascular endothelial cells to determine which events occurring during angiogenesis are affected by this microbial angiogenesis inhibitor. 15-Deoxyspergualin did not inhibit the production of urokinase-type plasminogen activator (u-PA) or type IV collagenase by vascular endothelial cells. The direct inhibition of u-PA activity by 15-deoxyspergualin was not observed either. The angiostatic antibiotic neither affected the migration of vascular endothelial cells nor inhibited the endothelial cell proliferation in a two-dimensional culture system. We also examined the effect of 15-deoxyspergualin on the proliferation of endothelial cells in a three-dimensional culture system involving collagen gel, in which cell growth resembles more closely the endothelial cell proliferation during in vivo angiogenesis than that in a two-dimensional culture system without collagen gel. The antibiotic inhibited cell proliferation in a dose-dependent manner, indicating that the three-dimensional culture system is useful for finding a new angiogenesis inhibitor with a different mode of action from those of angiogenesis inhibitors found by using a two-dimensional assay system; however, no cause-effect relationship has yet been established. Taken together, these results suggest the possible involvement of the inhibition of vascular endothelial cell growth by 15-deoxyspergualin in its angiogenesis-inhibitory effect. 15-Deoxyspergualin appears to be a promising candidate as an angiogenesis inhibitor for controlling aberrant angiogenic responses occurring in different states, including tumor development.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Oikawa
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: I
authors.initials: I
authors.lastname: Morita
authors.forename: S
authors.initials: S
authors.lastname: Murota
authors.forename: H
authors.initials: H
authors.lastname: Ashino
authors.forename: M
authors.initials: M
authors.lastname: Shimamura
authors.forename: A
authors.initials: A
authors.lastname: Kiue
authors.forename: R
authors.initials: R
authors.lastname: Hamanaka
authors.forename: M
authors.initials: M
authors.lastname: Kuwano
authors.forename: M
authors.initials: M
authors.lastname: Ishizuka
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9; D003012:Microbial Collagenase / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010960:Plasminogen Activators / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D006146:Guanidines; D010960:Plasminogen Activators; D003012:Microbial Collagenase; D020780:Matrix Metalloproteinase 9; C037258:gusperimus