Type-II estrogen binding sites in a lymphoblastoid cell line and growth-inhibitory effect of estrogen, anti-estrogen 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 microM. 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.
Scambia
G
G
Department of Gynecology, Catholic University, Rome, Italy.
Ranelletti
F O
FO
Benedetti Panici
P
P
Piantelli
M
M
Rumi
C
C
Battaglia
F
F
Larocca
L M
LM
Capelli
A
A
Mancuso
S
S
D001667:Binding, Competitive; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004054:Diethylstilbestrol / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006131:Growth Inhibitors; D006801:Humans; D016130:Immunophenotyping; D008214:Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D011960:Receptors, Estrogen / Q000032:analysis* / Q000145:classification; D013629:Tamoxifen / Q000494:pharmacology
D005419:Flavonoids; D006131:Growth Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004054:Diethylstilbestrol