Abstract #122: Mechanisms of Hyperforin as an anti-angiogenic angioprevention agent

Hyperforin, the major lipophilic compound contained in extracts of Hypericum perforatum, is responsible for the antidepressant activity associated with the extract. Recently several other biological properties of Hyperforin have been unveiled, including inhibition of tumor invasion and angiogenesis. The mechanism of the anti-angiogenic activity of hyperforin remains to be fully elucidated. We show that treatment with non-cytotoxic concentrations of Hyperforin restrains in a dose-dependent mannerthe capacity of to migrate towards relevant chemotactic stimuli. Hyperforin inhibited the ability of HUVE endothelial cells to organize into capillary-like structures in vitro. Further, it potently inhibited angiogenesis in vivo in the Matrigel sponge assay in response to diverse angiogenic agents. Immunofluorescent staining showed that in cytokine-activated endothelial HUVE cells Hyperforin inhibits translocation to the nucleus of NF-\#954;B, a transcription factor regulating numerous genes involved in cell growth, survival, angiogenesis and invasion, western blotting suggested that Hyperforin also repressed pErk1/2 activation as well. Under Hyperforin treatment in vivo, the growth of Kaposi\#8217;s sarcoma - a highly angiogenic tumor - was strongly inhibited, with the resultant tumors remarkably reduced in size and in vascularization as compared with controls. Hyperforin has also been reported too have anti-inflammatory properties, here we demonstrated that hyperforin was able to inhibit neutrophil and monocyte chemotaxis in vitro. Further, Hyperforin inhibited the inflammatory angiogenesis induced by these two compounds in vivo. These results highlight the potential for Hyperforin as a angioprevention agent, acting as strong inhibitor of inflammation-assoaciated tumor angiogenesis, and provide new therapeutic approaches to halting angiogenesis associated pathologies.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 122.