1,2,3,4,6-Penta-O-galloyl-beta-D-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2

Title1,2,3,4,6-Penta-O-galloyl-beta-D-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2
Publication TypeJournal Article
Year of Publication2013
AuthorsCryan, L. M., Bazinet L., Habeshian K. A., Cao S., Clardy J., Christensen K. A., and Rogers M. S.
JournalJ Med Chem
Date PublishedMar 14
ISBN Number1520-4804 (Electronic)<br/>0022-2623 (Linking)
Accession Number23394144
KeywordsAngiogenesis Inhibitors/*pharmacology, Animals, Cell Line, Tumor, Cell Proliferation/drug effects, Endothelial Cells/drug effects, Humans, Hydrolyzable Tannins/*pharmacology, Mice, Neovascularization, Pathologic/*drug therapy, Receptors, Peptide/*antagonists & inhibitors/physiology

Capillary morphogenesis gene 2 (CMG2) is a transmembrane extracellular matrix binding protein that is also an anthrax toxin receptor. We have shown that high-affinity CMG2 binders can inhibit angiogenesis and tumor growth. We recently described a high-throughput FRET assay to identify CMG2 inhibitors. We now report the serendipitous discovery that PGG (1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose) is a CMG2 inhibitor with antiangiogenic activity. PGG is a gallotannin produced by a variety of medicinal plants that exhibits a wide variety of antitumor and other activities. We find that PGG inhibits CMG2 with a submicromolar IC50 and it also inhibits the migration of human dermal microvascular endothelial cells at similar concentrations in vitro. Finally, oral or intraperitoneal administration of PGG inhibits angiogenesis in the mouse corneal micropocket assay in vivo. Together, these results suggest that a portion of the in vivo antitumor activity of PGG may be the result of antiangiogenic activity mediated by inhibition of CMG2.

Short Title1,2,3,4,6-Penta-O-galloyl-beta-D-glucopyranose Inhibits Angiogenesis via Inhibition of Capillary Morphogenesis Gene 2