Type II oestrogen binding sites in acute lymphoid and myeloid leukaemias: growth inhibitory effect of oestrogen and flavonoids

Br J Haematol. 1990 Aug;75(4):489-95. doi: 10.1111/j.1365-2141.1990.tb07787.x.

Abstract

The presence of oestrogen receptors (ER) and type II oestrogen binding sites (type II EBS) 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 239450 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 diethylstillboestrol (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 a 1 d 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Binding Sites
  • Bone Marrow / metabolism
  • Diethylstilbestrol / metabolism
  • Estrogens / analysis*
  • Flavonoids / metabolism
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / metabolism*
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Receptors, Estrogen / analysis*
  • Tumor Cells, Cultured

Substances

  • Estrogens
  • Flavonoids
  • Receptors, Estrogen
  • Diethylstilbestrol