Original Paper Pharmacology	Planta Med 2005; 71: 999-1004 DOI: 10.1055/s-2005-871303
© Georg Thieme Verlag KG Stuttgart · New York
Hyperforin acts as an Angiogenesis Inhibitor in vitro and in vivo
Christoph M. Schempp1,5, Judit Kiss2,5, Vladimir Kirkin3, Marco Averbeck4, Birgit Simon-Haarhaus1, Bernhard Kremer1, Christian C. Termeer1, Jonathan Sleeman3, Jan C. Simon4
1 Department of Dermatology, University of Freiburg, Freiburg, Germany 2 Department of Dermatology, Semmelweis University, Budapest, Hungary 3 Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe, Karlsruhe, Germany 4 Department of Dermatology, Venerology and Allergology, University of Leipzig, Leipzig, Germany 5 These authors contributed equally to this work

Abstract

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.

Key words

Angiogenesis - apoptosis - endothelial cells - microvessels - CD31