Collins-Burow B M, Burow M E, Duong B N, McLachlan J A
Tulane-Xavier Center for Bioenvironmental Research, Department of Pharmacology, Tulane University Medical Center, New Orleans, LA 70112, USA.
Nutr Cancer. 2000;38(2):229-44. doi: 10.1207/S15327914NC382_13.
Members of the flavonoid class of phytochemicals have previously been demonstrated to possess estrogenic activity in a number of hormonally responsive systems. We have performed the present study to characterize the estrogenic and antiestrogenic activity of flavonoids in the estrogen receptor (ER)-positive MCF-7 human breast cancer cell line. Using an ER-dependent reporter gene assay and an ER competition binding assay, we have identified phytochemicals possessing estrogenic and antiestrogenic activities, which appeared to correlate directly with their capacity to displace [3H]estradiol from ER. Several flavonoids, including kaempferide, apigenin, and flavone, were distinct, in that their antiestrogenic activity did not appear to correlate with binding to ER, and therefore their suppression of estrogen-mediated gene transactivation and proliferation may occur independent of direct antagonism of the receptor. Further examination in HEK-293 cells transfected with ERalpha or ERbeta demonstrated potent antagonism with kaempferide and apigenin, while flavone was weakly antagonistic only toward ERP. These results suggest that the receptor binding-independent antiestrogenic chemicals may function through alternate signaling pathways as indirect ER modulators in a receptor- and cell type-specific manner. We conclude that antiestrogenic activities of flavonoid phytochemicals may occur through ER binding-dependent and -independent mechanisms and that the binding-independent antiestrogen activity of certain flavonoids is biologically significant in regulation of breast cancer cell proliferation.
此前已证明，植物化学物质类黄酮的成员在许多激素反应系统中具有雌激素活性。我们开展了本研究，以表征类黄酮在雌激素受体（ER）阳性的MCF-7人乳腺癌细胞系中的雌激素和抗雌激素活性。通过使用ER依赖性报告基因测定法和ER竞争结合测定法，我们鉴定出了具有雌激素和抗雌激素活性的植物化学物质，这些活性似乎与其从ER置换[3H]雌二醇的能力直接相关。几种类黄酮，包括山柰素、芹菜素和黄酮，情况有所不同，因为它们的抗雌激素活性似乎与与ER的结合无关，因此它们对雌激素介导的基因转录激活和增殖的抑制作用可能独立于受体的直接拮抗作用而发生。在转染了ERα或ERβ的HEK-293细胞中进行的进一步研究表明，山柰素和芹菜素具有强效拮抗作用，而黄酮仅对ERβ具有微弱的拮抗作用。这些结果表明，与受体结合无关的抗雌激素化学物质可能通过替代信号通路发挥作用，作为受体和细胞类型特异性的间接ER调节剂。我们得出结论，类黄酮植物化学物质的抗雌激素活性可能通过依赖ER结合和不依赖ER结合的机制发生，并且某些类黄酮不依赖结合的抗雌激素活性在调节乳腺癌细胞增殖中具有生物学意义。
