TYPE-II ESTROGEN BINDING-SITES IN A LYMPHOBLASTOID CELL-LINE AND GROWTH-INHIBITORY EFFECT OF ESTROGEN, ANTIESTROGEN AND BIOFLAVONOIDS

Type‐II estrogen‐binding sites (type‐II EBS) have been demonstrated in the human lymphoblastoid cell line IM‐9 using a whole‐cell assay with (6, 7‐3H) estradiol (3H‐E2) as tracer. Competition analysis showed that the anti‐estrogen tamoxifen and the flavonoids quercetin and rutin competed for (3H)‐E2 binding to type‐II EBS. Growth experiments demonstrated that diethylstilbestrol (DES) tamoxifen (TAM), quercetin and rutin exerted a reversible dose‐dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 μM. The relative binding affinity of quercetin, rutin, DES and TAM for type‐II EBS correlated well with their potency as cell growth inhibitors. Moreover, hesperidin, a flavonoid which does not bind to type‐II EBS, was ineffective in inhibiting cell growth. Cell‐cycle analysis showed that the growth‐inhibitory effect of DES, TAM or quercetin was due to a blocking effect in the G0‐G1 phases. Our results suggest that high estrogen and anti‐estrogen concentrations and flavonoids may regulate IM‐9 cell growth through a common mechanism involving a binding interaction with type‐II EBS. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company