Novel tempeh (fermented soyabean) isoflavones inhibit in vivo angiogenesis in the chicken chorioallantoic membrane assay.
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.
Kiriakidis
Serafim
S
Institute of Pathology, University of Bonn, Bonn, Germany. s.kiriakidis@imperial.ac.uk
Högemeier
Oliver
O
Starcke
Susanne
S
Dombrowski
Frank
F
Hahne
Jens Claus
JC
Pepper
Michael
M
Jha
Hem Chandra
HC
Wernert
Nicolas
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D050783:Proto-Oncogene Proteins c-ets; D045730:Soy Foods; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology
C502164:6,7,4'-trihydroxyisoflavone; C502165:7,8,4'-trihydroxyisoflavone; D020533:Angiogenesis Inhibitors; C494041:ETS1 protein, human; D007529:Isoflavones; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C004742:daidzein; D019833:Genistein