Quercetin-3-O-glucronide inhibits noradrenaline binding to α2-adrenergic receptor, thus suppressing DNA damage induced by treatment with 4-hydroxyestradiol and noradrenaline in MCF-10A cells.

摘要: Risk factors for breast cancer include estrogens such as 17β-estradiol (E2) and high stress levels. 4-Hydroxyestradiol (4-OHE2), a metabolite of E2 formed preferentially by cytochrome P450 1B1, is oxidized to E2-3,4-quinone, which reacts with DNA form depurinating adducts that exert genotoxicity carcinogenicity. Endogenous catecholamines adrenaline (A) noradrenaline (NA) are released from the adrenal gland sympathetic nervous system during exposure stress. Here, we found treatment 4-OHE2 (3 μM) NA nM) significantly induced phosphorylation histone H2AX (γ-H2AX), one earliest indicators damage, apurinic (AP) sites via α2-adrenergic receptor (α2-AR) in human mammary epithelial MCF-10A cells. As an inverse association between higher intake flavonoids risk has previously been suggested epidemiological studies, investigated effects quercetin-3-O-glucuronide (Q3G), circulating quercetin blood, on 4-OHE2- NA-induced γ-H2AX AP sites. Q3G (0.1 suppressed their induction inhibited binding [(3)H]-NA α2-AR. These results suggest acts α2-AR antagonist it could be used chemopreventive agent stress-promoted cancer.