Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation.
The effect of the isoflavones, genistein, daidzein, and biochanin A on the growth of the LNCaP and DU-145 human prostate cancer cell lines has been examined. Genistein and biochanin A, but not daidzein, inhibit both serum and EGF-stimulated growth of LNCaP and DU-145 cells (IC50 values from 8.0 to 27 micrograms/ml for serum and 4.3 to 15 micrograms/ml for EGF), but have no significant effect of the EGF receptor tyrosine autophosphorylation. In contrast, tyrphostin 25, a specific EGF receptor tyrosine kinase inhibitor, inhibits EGF-stimulated growth and EGF receptor tyrosine autophosphorylation in these whole cells, but does not inhibit serum-stimulated growth. These data suggest that the mechanism of action of genistein and biochanin A does not depend on inhibition of EGF receptor tyrosine autophosphorylation, but on a more distal event in the EGF receptor-mediated signal transduction cascade.
Peterson
G
G
Department of Biochemistry, University of Alabama, Birmingham 35294-0019.
Barnes
S
S
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins
D016588:Anticarcinogenic Agents; D002396:Catechols; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D009570:Nitriles; D020032:Tyrphostins; C060152:tyrphostin 47; D014443:Tyrosine; D004815:Epidermal Growth Factor; C004742:daidzein; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C004541:biochanin A