Quercetin induces type‐II estrogen‐binding sites in estrogen‐receptor‐negative (MDA‐MB231) and estrogen‐receptor‐positive (MCF‐7) human breast‐cancer cell lines

Abstract

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.

The BPV-4 co-carcinogen quercetin induces cell cycle arrest and up-regulates transcription from the LCR of BPV-4

“…Given a di erent outcome of quercetin exposure depending on cell type and culture conditions, we asked what e ect quercetin would have on the growth of PalF cells. Indeed PalF cells do undergo growth arrest when exposed to quercetin concentrations (20 ± 100 mM) similar to those reported for established cells (60 ± 120 mM; Plauman et al, 1996) but considerably higher than for tumour cells (1 nM ± 1 mM; Scambia et al, 1993;Piantelli et al, 1995), con®rming that the genetic background of the cell determines at least in part its response to thē avonoid. During the ®rst 12 h of quercetin treatment at higher doses (50 and 100 mM) almost twice as many PalF cells are in S phase than untreated cells.…”

“…Thus it behaves as an initiator in a two stage in vitro cell transformation model (Sakai et al, 1990) and potentiates the carcinogenic activity of azoxymethane in rats (Pereira et al, 1996), but it inhibits the action of TPA in mice (Kato et al, 1983) and causes cell growth arrest in a variety of tumour or established cell types (Hosokawa et al, 1990;Ranelletti et al, 1992;Scambia et al, 1993;Piantelli et al, 1995;Avila et al, 1994;Plaumann et al, 1996). Its cytostatic e ect has prompted the proposal that quercetin be used as an anticancer agent .…”

Quercetin suppresses HeLa cell viability via AMPK‐induced HSP70 and EGFR down‐regulation

“…Quercetin inhibits the growth of malignant cells via the following mechanisms: inhibition of glycolysis, synthesis of macromolecules and enzymes; arresting the cell cycle; and interaction with estrogen type II binding sites (Verma et al, 1988;Hosokawa et al, 1990Hosokawa et al, , 1992Koishi et al, 1992;Scambia et al, 1992Scambia et al, , 1993. In addition, this flavone inhibits the induction of heat shock proteins (HSPs) and thermotolerance without affecting the synthesis of other proteins (Hosokawa et al, 1990Koishi et al, 1992;Scambia et al, 1993).…”

“…0 ,4 0 ,5,7-pentahydroxy flavones), is an efficient anti-oxidant (Pietta, 2000;Wu et al, 2005) and one of the most widely distributed bioflavonoids in the plant kingdom (Verma et al, 1988;Hosokawa et al, 1990Hosokawa et al, , 1992Scambia et al, 1992Scambia et al, , 1993Wei et al, 1994). Quercetin has anti-tumor activities for a variety of tumor cells, including leukemia, colon carcinoma, ovarian carcinoma, breast cancer, and lymphoma Avila et al, 1994;Larocca et al, 1995;LaVoie and Witorsch, 1995;Osman et al, 1995;Prajda et al, 1995).…”

The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor

“…For this purpose, two clones of the human osteosarcoma cell line U2-OS were used, transfected with ERa or ERb, expressing physiological levels of either of these receptors [24]. Furthermore, the effect of quercetin on ER-mediated cell proliferation was investigated using the ER-positive cell lines MCF-7 and T47D [25], as well as the ER-negative cell lines MDA-MB231 [26] and HCC-38 [27]. To validate the conclusions, the effects of quercetin on cell proliferation obtained in all these cell systems were compared with the effects obtained for the model phytoestrogen genistein .…”