诱导的葛根产生的植物抗毒素块根素对雌激素受体活性的调节作用
Modulation of Estrogen Receptor Activity by the Phytoalexin Tuberosin Produced from Elicited Kudzu ().
作者信息
Belgodere Jorge A, Elliott Jack R, Benz Megan C, Kpeli G Wills, Elliott Steven, Ponder Isaac J, Sanga Pema Geoffroy E R, Ma Peng, Dietrich Sophie R, Cheng Thomas, Nguyen Khoa, Tilghman Syreeta L, Zou Binghao, Anbalagan Muralidharan, Rowan Brian G, Newman Robert H, Mondrinos Mark, Sridhar Jayalakshmi, Wiese Thomas E, Ali Simak, Hoang Van T, Collins-Burow Bridgette M, Martin Elizabeth C, Abbas Hamed K, Boué Stephen M, Burow Matthew E
机构信息
Tulane Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Science Center, New Orleans, Louisiana 70112, United States.
Department of Biological and Agricultural Engineering, Louisiana State University and Agricultural Center, Baton Rouge, Louisiana 70803, United States.
出版信息
J Nat Prod. 2025 Jul 25;88(7):1568-1580. doi: 10.1021/acs.jnatprod.5c00192. Epub 2025 Jun 20.
Kudzu's invasive nature has contributed to its classification as a weed, as it frequently outcompetes native plant species, leading to extensive overgrowth. Efforts to control kudzu have proven challenging, with moderate success using physical or biological agents. In this study, we evaluated the effects of two such control agents, ultraviolet C radiation and , to significantly increase the production of tuberosin, a phytoalexin isoflavone. Our findings demonstrate that estrogenic activity of tuberosin is cell-type-dependent, displaying antagonist or competitive inhibition when combined with 17-β-estradiol in the estrogen receptor (ER) positive cell lines MCF-7 and T-47D, while showing dose-dependent agonist activity in HEK293 cells transfected to express both ER receptors (α and β). Tuberosin was shown to modulate ER pathways, alter ER-mediated gene expression, and increase cell proliferation in a dose-dependent manner while maintaining expression of the ERα protein. Binding affinity and docking simulations confirmed tuberosin binding to the ERα pocket in a similar but weaker manner compared to synthetic estrogen. Tuberosin-treated endothelial cells suppressed vascular network assembly and maturation without affecting the cellular proliferative capacity. The presented studies leverage current kudzu management methods to naturally produce tuberosin, examine cell-type-specific effects, and support further investigation as an antiestrogen for breast cancer treatment.
葛根的入侵性使其被归类为杂草,因为它经常比本土植物物种更具竞争力,导致大面积过度生长。事实证明,控制葛根具有挑战性,使用物理或生物制剂取得了一定成效。在本研究中,我们评估了两种此类控制剂,紫外线C辐射和……的效果,以显著增加块根菌素(一种植物抗毒素异黄酮)的产量。我们的研究结果表明,块根菌素的雌激素活性取决于细胞类型,在雌激素受体(ER)阳性细胞系MCF-7和T-47D中与17-β-雌二醇结合时表现出拮抗剂或竞争性抑制作用,而在转染以表达两种ER受体(α和β)的HEK293细胞中表现出剂量依赖性激动剂活性。块根菌素被证明可调节ER途径,改变ER介导的基因表达,并以剂量依赖性方式增加细胞增殖,同时维持ERα蛋白的表达。结合亲和力和对接模拟证实,与合成雌激素相比,块根菌素以类似但较弱的方式与ERα口袋结合。用块根菌素处理的内皮细胞抑制了血管网络的组装和成熟,而不影响细胞的增殖能力。本研究利用当前的葛根管理方法自然产生块根菌素,研究细胞类型特异性效应,并支持将其作为乳腺癌治疗的抗雌激素进行进一步研究。