TYPE-II ESTROGEN BINDING-SITES IN ACUTE LYMPHOID AND MYELOID LEUKEMIAS - GROWTH INHIBITORY EFFECT OF ESTROGEN AND FLAVONOIDS

Summary. The presence of oestrogen receptors (ER) and type II oestrogen binding sites (type IIEBS) have been investigated by a whole cell assay in seven cases of acute lymphoid leukaemia (ALL) and 16 cases of acute myeloid leukaemia (AML). ER were detected in 6/7 ALL patients with values ranging between 133 and 2268 sites/cell and in 12/16 AML patients with values ranging between 274 and 4197 sites/cell. The apparent dissociation constant (KD) for ER was 0.6±0.3 nM (mean + SD of 20 cases). All blasts from ALL and AML patients expressed type II EBS at variable levels ranging between 3109 and 239 450 sites/cell. The mean (KD) value for these sites was 18.3±5.6 nM (mean±SD of 23 cases). Specificity experiments demonstrated that type II EBS are oestrogen specific relative to the class of steroid hormones. In addition, the flavonol quercetin was able to compete for [3H]17 beta‐oestradiol (E2) binding to type II EBS, the relative binding affinity (RBA) of quercetin being greater than that of diethylstilboestrol (DES). DES and quercetin exerted a dose‐dependent inhibition of ALL and AML blast proliferation in the range of concentrations between 10‐8 and 10‐5 M. The RBA of DES and quercetin for type II EBS correlated well with their potency as cell growth inhibitors. Moreover, the flavonols rutin and hesperidin which compete slightly for [3H]E2 binding to type II EBS, were scarcely effective in inhibiting leukaemic cell proliferation. The inhibitory effect of DES and quercetin was not due to a non‐specific cytotoxic action since after aid culture period, cell viability did not vary between control and treated cells, being greater than 80%. Our results suggest that high oestrogen concentrations and the flavonol quercetin may inhibit leukaemic blast proliferation through a common mechanism involving a binding interaction with type II EBS. Copyright © 1990, Wiley Blackwell. All rights reserved