Mechanisms of Hyperforin as an anti-angiogenic angioprevention agent.

Details

Serval ID
serval:BIB_BC39EC8B10F4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mechanisms of Hyperforin as an anti-angiogenic angioprevention agent.
Journal
European journal of cancer
Author(s)
Lorusso G., Vannini N., Sogno I., Generoso L., Garbisa S., Noonan D.M., Albini A.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
05/2009
Peer-reviewed
Oui
Volume
45
Number
8
Pages
1474-1484
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 tumour 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 manner, the capacity of endothelial cells to migrate towards relevant chemotactic stimuli. Hyperforin inhibits the organisation of HUVE endothelial cells in capillary-like structures in vitro, and potently represses angiogenesis in vivo in the Matrigel sponge assay in response to diverse angiogenic agents. Immunofluorescent staining shows that in cytokine-activated endothelial HUVE cells Hyperforin prevents translocation to the nucleus of NF-kappaB, a transcription factor regulating numerous genes involved in cell growth, survival, angiogenesis and invasion. Under Hyperforin treatment in vivo, the growth of Kaposi's sarcoma - a highly angiogenic tumour - is strongly inhibited, with the resultant tumours remarkably reduced in size and in vascularisation as compared with controls. Hyperforin has also been reported to have anti-inflammatory properties. Here we show that Hyperforin inhibits neutrophil and monocyte chemotaxis in vitro and angiogenesis in vivo induced by angiogenic chemokines (CXCL8 or CCL2). These results highlight the potential for Hyperforin as an anti-inflammatory angioprevention agent, acting as a strong inhibitor of inflammation- or tumour-triggered angiogenesis, and provide new therapeutic approaches to halting pathology-associated angiogenesis.
Keywords
Analysis of Variance, Angiogenesis Inhibitors/therapeutic use, Animals, Apoptosis/drug effects, Bridged Bicyclo Compounds/therapeutic use, Cell Line, Tumor, Cell Movement/drug effects, Endothelial Cells/drug effects, Endothelial Cells/pathology, Humans, Male, Mice, Mice, Nude, Microscopy, Fluorescence, Neoplasms/blood supply, Neoplasms/drug therapy, Neovascularization, Pathologic, Phloroglucinol/analogs & derivatives, Phloroglucinol/therapeutic use, Terpenes/therapeutic use, Xenograft Model Antitumor Assays
Pubmed
Web of science
Create date
31/01/2022 9:23
Last modification date
01/02/2022 6:36
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