Quercetin induces type-II estrogen-binding sites in estrogen-receptor-negative (MDA-MB231) and estrogen-receptor-positive (MCF-7) human breast-cancer cell lines.
We show that flavonoids positively regulate type-II estrogen-binding site (type-II EBS) levels both in MCF-7 (ER-positive) and in MDA-MB231 (ER-negative) breast-cancer cells. Type-II EBS were measured by a whole-cell assay at 4 degrees C for 2.5 hr using [3H]-estradiol as tracer. In both cell lines the effect of quercetin (Q) was dose-related and already evident after 12 hr of Q treatment. The increase of type-II EBS levels after Q exposure requires both RNA and protein synthesis, since actinomycin D and cycloheximide completely abolished the stimulatory effect. The ability of flavonoids in inducing type-II EBS is well correlated with their relative binding affinity for type-II EBS. The flavonoid-induced enhancement of type-II EBS levels is accompanied by increased sensitivity of cancer cells to the inhibitory effect of low Q concentrations. Our data suggest that type-II EBS are ligand-regulated receptors.
Scambia
G
G
Department of Gynecology, Catholic University, Rome, Italy.
Ranelletti
F O
FO
Panici
P B
PB
Piantelli
M
M
De Vincenzo
R
R
Ferrandina
G
G
Bonanno
G
G
Capelli
A
A
Mancuso
S
S
D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D002455:Cell Division / Q000187:drug effects; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D011794:Quercetin / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004967:Estrogens; D005419:Flavonoids; D011960:Receptors, Estrogen; D011794:Quercetin