Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

Abstract

Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E2). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E2-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E2 pellets, co-exposure to quercetin did not protect rats from E2-induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E2-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E2 group relative to those in the E2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin exposed mammary tissue. Analysis of 8-isoprostane F2α (8-iso-PGF2α) levels as a marker of oxidant stress showed that quercetin did not decrease E2-induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E2-induced oxidant stress and may exacerbate breast carcinogenesis in E2-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E2-induced breast tumors in female ACI rats.

Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells

“…Breast tumors were developed in female August-Copenhagen Irish (ACI) rats by given quercetin (2.5 g/kg food) for 8 months in combination with treatment of estradiol, a powerful female hormone. Further experiments showed that this might be due to inhibiting the metabolism of estradiol by quercetin in rats [36]. In 1996, David et al [37] have performed Phase I clinical trial with quercetin in humans.…”

Quercetin dietary supplementation of fattening lambs at 0.2% rate reduces discolouration and microbial growth in meat during refrigerated storage

“…No significant differences among dietary treatments were observed in hot or cold carcass weight but a significant increase in kidney knob fat was observed in the lambs being fed flaxseed and/or quercetin when BW was used as covariable. Phytoestrogens such as quercetin are plant compounds that structurally mimic the endogenous oestrogen 17beta-estradiol (Singh et al, 2010). In this sense, it has been demonstrated that estradiol induces a significant increase in all subcutaneous fat depots (Elbers, Asscheman, Seidell, & Gooren, 1999), which might explain the significant increase in kidney knob fat observed in the lambs being fed quercetin when compared to the CTRL lambs ( Table 2).…”

4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, 1 a novel resveratrol analog, differentially regulates estrogen receptors α and β in breast cancer cells

“…The expression levels of ERα or β relative to cyclophilin were determined as reported recently [30]. A standard curve was run on each plate to allow for accurate quantification of cDNA, as reported previously [31–37]. …”

“…Western blot analyses were performed as described previously [31–37]. Affinity purified rabbit polyclonal antibodies against ERα (Santa Cruz, sc-543), ERβ (Santa Cruz, sc-8974), c-Myc (Santa Cruz, sc-788), cyclin D1 (Santa Cruz, sc-753), p53 (Santa Cruz, sc-55476) and p21 (Santa Cruz, sc-6264) were diluted in PBS/0.05% Tween-20 and used for immune-detection as reported recently [30].…”