Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors.
We studied the effect of quercetin (Q) on the proliferation of HT-29, WiDr, COLO 201, and LS-174T human colon cancer cell lines. Q, between 10 nM and 10 microM, exerted a dose-dependent, reversible inhibition of cell proliferation. Cell-cycle analysis revealed that the growth-inhibitory effect of Q was due to a blocking action in the G0/G1 phase. Using a whole-cell assay with 17 beta-[3H]-estradiol as tracer, we demonstrated that all these cell lines contain type-II estrogen-binding sites (type-II EBS). By using Q and other chemically related flavonols (3,7-4'-trimethoxyquercetin, 3,7,3',4'-tetramethoxyquercetin, kaempferol, morin, and rutin), we observed that the affinities of these compounds for type-II EBS are correlated with their growth-inhibitory potential. Furthermore, the Q sensitivity of the colon cancer cell lines was correlated with the number of type-II EBS/cell. Then Q could regulate colon cancer cell growth through a binding interaction with type-II EBS. This mechanism could also be active in vivo as we have observed that cytosolic type-II EBS are present in primary colorectal cancers and that Q is effective in inhibiting the in vitro bromodeoxyuridine incorporated by neoplastic cells in these cancers.
Ranelletti
F O
FO
Department of Histology, Università Cattolica S. Cuore, Rome, Italy.
Ricci
R
R
Larocca
L M
LM
Maggiano
N
N
Capelli
A
A
Scambia
G
G
Benedetti-Panici
P
P
Mancuso
S
S
Rumi
C
C
Piantelli
M
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004958:Estradiol / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D011794:Quercetin / Q000494:pharmacology*; D013256:Steroids / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D013256:Steroids; D004958:Estradiol; D011794:Quercetin