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Novel tempeh (fermented soyabean) isoflavones inhibit in vivo angiogenesis in the chicken chorioallantoic membrane assay

Published online by Cambridge University Press:  08 March 2007

Serafim Kiriakidis ,
Oliver Högemeier ,
Susanne Starcke ,
Frank Dombrowski ,
Jens Claus Hahne ,
Michael Pepper ,
Hem Chandra Jha  and
Nicolas Wernert
Serafim Kiriakidis*
Affiliation:
Institute of Physiological Chemistry and
Oliver Högemeier
Affiliation:
Institute of Pathology, University of Bonn, Bonn, Germany
Susanne Starcke
Affiliation:
Institute of Physiological Chemistry and
Frank Dombrowski
Affiliation:
Institute of Pathology, University of Bonn, Bonn, Germany
Jens Claus Hahne
Affiliation:
Institute of Pathology, University of Bonn, Bonn, Germany
Michael Pepper
Affiliation:
Department of Morphology, University of Geneva Medical Center, Geneva, Switzerland
Hem Chandra Jha
Affiliation:
Institute of Physiological Chemistry and
Nicolas Wernert
Affiliation:
Institute of Pathology, University of Bonn, Bonn, Germany
*
*Corresponding author: Dr Serafim Kiriakidis, fax +44 20 8383 4499, email [email protected]
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Abstract

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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 angiogensis 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.

Keywords

SoyabeanTempehIsoflavonesAngiogenesisEts 1
Type
Research Article
Information
British Journal of Nutrition , Volume 93 , Issue 3 , March 2005 , pp. 317 - 323
Copyright
Copyright © The Nutrition Society 2005

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