Modulation of estrogen receptor activity by the phytoalexin tuberosin produced from elicited kudzu Pueraria lobata
File(s)
Author(s)
Type
Journal Article
Abstract
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 Myrothecium verrucaria, 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.
Date Issued
2025-07-25
Date Acceptance
2025-06-09
Citation
Journal of Natural Products, 2025, 88 (7), pp.1568-1580
ISSN
0163-3864
Publisher
American Chemical Society (ACS)
Start Page
1568
End Page
1580
Journal / Book Title
Journal of Natural Products
Volume
88
Issue
7
Copyright Statement
© 2025 The Authors. Published by American Chemical Society and American Society of Pharmacognosy. This publication is licensed under CC-BY 4.0 .
License URL
Subjects
Humans
Pueraria
Sesquiterpenes
Isoflavones
Receptors, Estrogen
Estrogen Receptor alpha
Cell Proliferation
Molecular Structure
HEK293 Cells
MCF-7 Cells
Phytoalexins
Publication Status
Published
Date Publish Online
2025-06-20