Udagawa T, Yuan J, Panigrahy D, Chang YH, Shah J, D'Amato RJ.
Cytochalasin E, an epoxide containing
Aspergillus-derived fungal metabolite, inhibits angiogenesis and
tumor growth.
J Pharmacol Exp Ther. 2000 Aug;294(2):421-7
Department of Surgical Research,
Children's Hospital, Harvard Medical School, Boston, MA, USA.
Several previously identified inhibitors of
angiogenesis have been epoxide-containing fungus-derived
metabolites. We therefore hypothesized that novel epoxide-containing
low molecular weight compounds structurally resembling known
antiangiogenic agents may also exhibit antiangiogenic activity.
Cytochalasin E was found to be a potent and selective inhibitor
of bovine capillary endothelial (BCE) cell proliferation.
Cytochalasin E differed from other cytochalasins by the presence
of an epoxide. The epoxide was required for activity, because
acid-catalyzed hydrolysis of the epoxide abrogated the
specificity and potency of cytochalasin E. Phalloidin staining
indicated that disruption of actin stress fibers by cytochalasin
E occurred only at relatively high concentrations. Lower
concentrations of cytochalasin E preferentially inhibited BCE
cell proliferation without disrupting actin stress fibers. In
vivo, cytochalasin E inhibited angiogenesis induced by basic
fibroblast growth factor by 40% to 50% in the mouse cornea assay
and inhibited the growth of Lewis lung tumors by approximately
72%. Cytochalasin E is a potent antiangiogenic agent that may
hold promise for the treatment of cancer and other types of
pathologic angiogenesis.
PMID: 10900214 |
