Ung D, Nagar S
Pharmaceutical Sciences, Temple University, Philadelphia, PA 19140, USA.
Xenobiotica. 2009 Jan;39(1):72-9. doi: 10.1080/00498250802604082.
High concentrations of endogenous oestradiol (E2) correlate with the proliferation of cancer cells. Resveratrol (a dietary chemopreventive agent) at high concentrations has an anti-oestrogenic effect. E2 and resveratrol are conjugated via common uridine diphosphoglucuronosyltransferase (UGT) and sulfotransferases (SULT) enzymes. Experiments were conducted in MCF-7 mammalian cells stably expressing human SULT1A1 or SULT1E1 to observe the effect of resveratrol on E2-mediated cell proliferation. The combination of E2 and resveratrol did have a proliferative effect in cells expressing SULT1E1, but not in those expressing SULT1A1. The effect of resveratrol (1-500 microM) on the glucuronidation of E2 (0.25-2.25 microM) was characterized in human liver microsomes. The highest resveratrol concentration significantly decreased the intrinsic clearance of E2 glucuronidation. The results corroborate the reported significant inhibition of SULT1E1-mediated E2 sulfation in vitro by resveratrol. Thus, resveratrol may interact with E2 in vivo by inhibiting its conjugation.
高浓度的内源性雌二醇（E2）与癌细胞增殖相关。高浓度的白藜芦醇（一种膳食化学预防剂）具有抗雌激素作用。E2和白藜芦醇通过共同的尿苷二磷酸葡萄糖醛酸基转移酶（UGT）和磺基转移酶（SULT）进行结合。在稳定表达人SULT1A1或SULT1E1的MCF-7哺乳动物细胞中进行实验，以观察白藜芦醇对E2介导的细胞增殖的影响。E2和白藜芦醇的组合在表达SULT1E1的细胞中确实具有增殖作用，但在表达SULT1A1的细胞中则没有。在人肝微粒体中表征了白藜芦醇（1 - 500微摩尔）对E2（0.25 - 2.25微摩尔）葡萄糖醛酸化的影响。最高白藜芦醇浓度显著降低了E2葡萄糖醛酸化的内在清除率。结果证实了报道的白藜芦醇在体外对SULT1E1介导的E2硫酸化有显著抑制作用。因此，白藜芦醇可能通过抑制其结合在体内与E2相互作用。
