Hyperforin acts as an angiogenesis inhibitor.
Hyperforin is a plant compound from Hypericum perforatum that inhibits tumor cell proliferation in vitro by induction of apoptosis. Here, we report that hyperforin also acts as an angiogenesis inhibitor in vitro and in vivo. In vitro, hyperforin blocked microvessel formation of human dermal microvascular endothelial cells (HDMEC) on a complex extracellular matrix. Furthermore, hyperforin reduced proliferation of HDMEC in a dose-dependent manner, without displaying toxic effects or inducing apoptosis of the cells. To evaluate the antiangiogenic activity of hyperforin in vivo, Wistar rats were subcutaneously injected with MT-450 mammary carcinoma cells and were treated with peritumoral injections of hyperforin or solvent. Hyperforin significantly inhibited tumor growth, induced apoptosis of tumor cells and reduced tumor vascularization, as shown by in situ staining of CD31-positive microvessels in the tumor stroma. These data suggest that, in addition to the induction of tumor cell apoptosis, hyperforin can also suppress angiogenesis by a direct, non-toxic effect on endothelial cells.
Schempp
Christoph M
CM
Department of Dermatology, University of Freiburg, Germany. cschempp@haut.ukl.uni-freiburg.de
Kiss
Judit
J
Kirkin
Vladimir
V
Averbeck
Marco
M
Simon-Haarhaus
Birgit
B
Kremer
Bernhard
B
Termeer
Christian C
CC
Sleeman
Jonathan
J
Simon
Jan C
JC
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D001643:Bridged Bicyclo Compounds; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin