Cytochalasin E, an epoxide containing Aspergillus-derived fungal metabolite, inhibits angiogenesis and tumor growth.

Abstract

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.

• Authors: T Udagawa, J Yuan, D Panigrahy, Y H Chang, J Shah, R J D'Amato
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 294 Issue 2 Pg. 421-7 (Aug 2000) ISSN: 0022-3565 [Print] United States
• PMID: 10900214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiogenesis Inhibitors
• Cyclohexanes
• Cytochalasins
• Endothelial Growth Factors
• Lymphokines
• Mycotoxins
• Sesquiterpenes
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• Fibroblast Growth Factor 2
• cytochalasin E
• Aminopeptidases
• methionine aminopeptidase 2
• Metalloendopeptidases
• O-(Chloroacetylcarbamoyl)fumagillol

Topics

• 3T3 Cells
• Aminopeptidases (antagonists & inhibitors)
• Angiogenesis Inhibitors (pharmacology)
• Animals
• Aspergillus (metabolism)
• Carcinoma, Lewis Lung (blood supply, drug therapy, pathology)
• Cell Division (drug effects)
• Cornea (blood supply)
• Cyclohexanes
• Cytochalasins (pharmacology)
• Endothelial Growth Factors (antagonists & inhibitors, pharmacology)
• Endothelium, Vascular (cytology, drug effects)
• Fibroblast Growth Factor 2 (antagonists & inhibitors, pharmacology)
• Humans
• Lymphokines (antagonists & inhibitors, pharmacology)
• Metalloendopeptidases (antagonists & inhibitors)
• Mice
• Mice, Inbred C57BL
• Mycotoxins (pharmacology)
• Neovascularization, Pathologic (drug therapy)
• Neovascularization, Physiologic (drug effects)
• O-(Chloroacetylcarbamoyl)fumagillol
• Sesquiterpenes (pharmacology)
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors