Abstract
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- β-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1940-1945 |
| Number of pages | 6 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 56 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 14 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Cite this
1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2. / Cryan, Lorna M.; Bazinet, Lauren; Habeshian, Kaiane; Cao, Shugeng; Clardy, Jon; Christensen, Kenneth A.; Rogers, Michael S.
In: Journal of Medicinal Chemistry, Vol. 56, No. 5, 14.03.2013, p. 1940-1945.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranose inhibits angiogenesis via inhibition of capillary morphogenesis gene 2
AU - Cryan, Lorna M.
AU - Bazinet, Lauren
AU - Habeshian, Kaiane
AU - Cao, Shugeng
AU - Clardy, Jon
AU - Christensen, Kenneth A.
AU - Rogers, Michael S.
PY - 2013/3/14
Y1 - 2013/3/14
N2 - 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- β-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.
AB - 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- β-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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84875158359&partnerID=8YFLogxK
U2 - 10.1021/jm301558t
DO - 10.1021/jm301558t
M3 - Article
C2 - 23394144
AN - SCOPUS:84875158359
VL - 56
SP - 1940
EP - 1945
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 5
ER -