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SECOND INTERNATIONAL SYMPOSIUM
ON THE ROLE OF SOY
IN PREVENTING AND TREATING CHRONIC DISEASESeptember 15-18, 1996
Brussells, Belgium
SCIENTIFIC PROGRAM
(Oral Abstracts)Soy and Cancer
Soybean Anticarcinogens / Anticancer MechanismsMechanisms of action of the soy isoflavone genistein at the cellular level
T.G. Peterson, H. Kim, and S. Barnes.
Department of Pharmacology & Toxicology, University of Alabama at Birmingham, AL 35294, USA.Genistein inhibits the proliferation of both normal and cancer cells induced by various growth factors and cytokines. There are several possible mechanisms which may be responsible for this action. It was originally shown in vitro with membrane preparations from mammalian cells that genistein was a potent and specific inhibitor of epidermal growth factor receptor (EGF-R) tyrosine autophosphorylation (Akiyama et al., J Biol Chem 262: 5592, 1987). This property as a protein tyrosine inhibitor has been widely suggested as a mechanism of action of genistein in its effects on cells. However, in intact cells genistein does not significantly alter EGF stimulation of tyrosine phosphorylation of EGF-R (Prostate 22: 335, 1993; Cell Growth & Differentiation, in press, 1996), or of several other tyrosine kinases thought to be involved in signal transduction pathways. Proposed alternative mechanisms include inhibition of DNA topoisomerase II activity, regulation of cell cycle checkpoints, and antiangiogenic and antioxidant activity. However, many of these mechanisms
require genistein concentrations in excess of 5 mM, the limit for plasma concentrations of genistein in those who eat a soy-based diet. New clues to a plausible mechanism for genistein's action come from examination of the familial chronic nose bleed disorder, hereditary hemorrhagic talengiectasia (HHT), a genetic disease involving mutations in the endoglin gene; endoglin is a protein involved in tranforming growth factor beta (TGFB) receptor complex formation. Consumption of a soy protein-based beverage (that includes genistein) drastically reduces the incidence of nosebleeds in many HHT patients (Korzenik et al., 1996). Since genistein inhibits cell cycle progression at G1/S, a checkpoint regulated by TGFB, genistein may have its beneficial effects on human cells by enhancing/augmenting TGFB-dependent control of cell cycling.
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