Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Anti-angiogenic strategies are emerging as an important tool for the treatment of cancer and inflammatory diseases. In the present investigation we isolated several isoflavones from a tempeh (fermented soyabean) extract. The isolated isoflavones were identified as 5,7,4'-trihydroxyisoflavone (genistein), 7,4'-dihydroxyisoflavone (daidzein), 6,7,4'-trihydroxyisoflavone (factor 2), 7,8,4'-trihydroxyisoflavone (7,8,4'-TriOH) and 5,7,3',4'-tetrahydroxyisoflavone (orobol). The effects on angiogenesis of these isoflavones were evaluated in the chicken chorioallantoic membrane assay; their capacity to inhibit vascular endothelial growth factor-induced endothelial cell proliferation and expression of the Ets 1 transcription factor, known to be implicated in the regulation of new blood vessel formation, were also investigated. We found that all isoflavones inhibited angiogenesis, albeit with different potencies. Compared with negative controls, which slightly inhibited in vivo angiogenesis by 6.30 %, genistein reduced angiogenesis by 75.09 %, followed by orobol (67.96 %), factor 2 (56.77 %), daidzein (48.98 %) and 7,8,4'-TriOH (24.42 %). These compounds also inhibited endothelial cell proliferation, with orobol causing the greatest inhibition at lower concentrations. The isoflavones also inhibited Ets 1 expression, providing some insight into the molecular mechanisms of their action. Furthermore, the chemical structure of the different isoflavones suggests a structure-activity relationship. Our present findings suggest that the new isoflavones might be added to the list of low molecular mass therapeutic agents for the inhibition of angiogenesis.

Type

Journal article

Journal

Br j nutr

Publication Date

03/2005

Volume

93

Pages

317 - 323

Keywords

Angiogenesis Inhibitors, Animals, Cell Proliferation, Chick Embryo, Chorioallantoic Membrane, Endothelium, Vascular, Genistein, Humans, Isoflavones, Neovascularization, Pathologic, Proto-Oncogene Protein c-ets-1, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ets, Soy Foods, Structure-Activity Relationship, Transcription Factors, Vascular Endothelial Growth Factor A