Quercetin inhibits the growth of a multidrug-resistant estrogen-receptor-negative MCF-7 human breast-cancer cell line expressing type II estrogen-binding sites.
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.
Scambia
G
G
Department of Gynecology, Catholic University, Largo A. Gemelli, Rome.
Ranelletti
F O
FO
Benedetti Panici
P
P
Piantelli
M
M
Bonanno
G
G
De Vincenzo
R
R
Ferrandina
G
G
Pierelli
L
L
Capelli
A
A
Mancuso
S
S
D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003864:Depression, Chemical; D004054:Diethylstilbestrol / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000037:antagonists & inhibitors; D004351:Drug Resistance / Q000502:physiology; D004354:Drug Screening Assays, Antitumor; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D011794:Quercetin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011960:Receptors, Estrogen; D013629:Tamoxifen / Q000493:pharmacokinetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D004967:Estrogens; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004054:Diethylstilbestrol; D004317:Doxorubicin; D011794:Quercetin