Quercetin induces type-II estrogen-binding sites in estrogen-receptor-negative (MDA-MB231) and estrogen-receptor-positive (MCF-7) human breast-cancer cell lines
Scambia, G.; Ranelletti, F.O.; Panici, P.B.; Piantelli, M.; De Vincenzo, R.; Ferrandina, G.; Bonanno, G.; Capelli, A.; Mancuso, S.
International Journal of Cancer 54(3): 462-466
ISSN/ISBN: 0020-7136 PMID: 8509221 DOI: 10.1002/ijc.2910540318
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.