Jc. Vera et al., GENISTEIN IS A NATURAL INHIBITOR OF HEXOSE AND DEHYDROASCORBIC ACID TRANSPORT THROUGH THE GLUCOSE-TRANSPORTER, GLUT1, The Journal of biological chemistry, 271(15), 1996, pp. 8719-8724
Genistein is a dietary-derived plant product that inhibits the activit
y of protein-tyrosine kinases, We show here that it is a potent inhibi
tor of the mammalian facilitative hexose transporter GLUT1, In human H
L-60 cells, which express GLUT1, genistein inhibited the transport of
dehydroascorbic acid, deoxyglucose, and methylglucose in a dose-depend
ent manner, Transport was not affected by daidzein, an inactive genist
ein analog that does not inhibit protein-tyrosine kinase activity, or
by the general protein kinase inhibitor staurosporine, Genistein inhib
ited the uptake of deoxyglucose and dehydroascorbic acid in Chinese ha
mster ovary (CHO) cells overexpressing GLUT1 in a similar dose-depende
nt manner, Genistein also inhibited the uptake of deoxyglucose in huma
n erythrocytes indicating that its effect on glucose transporter funct
ion is cell-independent, The inhibitory action of genistein on transpo
rt was instantaneous, with no additional effect observed in cells prei
ncubated with it for various periods of time, Genistein did not alter
the uptake of leucine by HL-60 cells, indicating that its inhibitory e
ffect was specific for the glucose transporters, The inhibitory effect
of genistein was of the competitive type, with a K-i of approximately
12 mu M for inhibition of the transport of both methylglucose and deo
xyglucose. Binding studies showed that genistein inhibited glucose-dis
placeable binding of cytochalasin B to GLUT1 in erythrocyte ghosts in
a competitive manner, with a K-i of 7 mu M. These data indicate that g
enistein inhibits the transport of dehydroascorbic acid and hexoses by
directly interacting with the hexose transporter GLUT1 and interferin
g with its transport activity, rather than as a consequence of its kno
wn ability to inhibit protein-tyrosine kinases, These observations ind
icate that some of the many effects of genistein on cellular physiolog
y may be related to its ability to disrupt the normal cellular flux of
substrates through GLUT1, a hexose transporter universally expressed
in cells, and is responsible for the basal uptake of glucose.