Quercetin inhibits the growth of a multidrug-resistant estrogen-receptor-negative MCF-7 human breast-cancer cell line expressing type II estrogen-binding sites.

Abstract

It has been demonstrated that the flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone; Q) inhibits the growth of several cancer cell lines. There is evidence suggesting that the antiproliferative activity of this substance is mediated by the so-called type II estrogen-binding site (type II EBS). We looked for the presence of type II EBS and the effect of Q on the proliferation of an Adriamycin-resistant estrogen-receptor-negative human breast-cancer cell line (MCF-7 ADRr). By whole-cell assay using estradiol labelled with 6,7-tritium [( 3H]-E2) as a tracer, we demonstrated that MCF-7 ADRr cells contain type II EBSs. Competition analysis revealed that diethylstilbestrol (DES) and Q competed with similar potency for [3H]-Es binding to type II EBSs. The antiestrogen tamoxifen (TAM) competed for type II EBSs, albeit to a lesser extent than either DES or Q. Growth experiments demonstrated that Q and DES exerted a dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM, whereas TAM was less effective. Q could also inhibit colony formation in a clonogenic assay. Our results indicate that multidrug-resistant estrogen-receptor-negative MCF-7 cells express type II EBSs and are sensitive to the inhibitory effect of Q. This substance could be the parent compound of a novel class of anticancer agents.

• Authors: G Scambia, F O Ranelletti, P Benedetti Panici, M Piantelli, G Bonanno, R De Vincenzo, G Ferrandina, L Pierelli, A Capelli, S Mancuso
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 28 Issue 4 Pg. 255-8 ( 1991) ISSN: 0344-5704 [Print] Germany
• PMID: 1879042 (Publication Type: Journal Article)

Chemical References

• Estrogens
• Receptors, Estrogen
• Tamoxifen
• Diethylstilbestrol
• Doxorubicin
• Quercetin

Topics

• Binding Sites (drug effects)
• Binding, Competitive (drug effects)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Division (drug effects)
• Cell Line
• Depression, Chemical
• Diethylstilbestrol (pharmacokinetics, pharmacology)
• Dose-Response Relationship, Drug
• Doxorubicin (antagonists & inhibitors)
• Drug Resistance (physiology)
• Drug Screening Assays, Antitumor
• Estrogens (metabolism)
• Female
• Humans
• Quercetin (pharmacokinetics, pharmacology, therapeutic use)
• Receptors, Estrogen
• Tamoxifen (pharmacokinetics, pharmacology)
• Tumor Cells, Cultured (cytology, drug effects, metabolism)