Modulation of Estrogen Receptor Activity by the Phytoalexin Tuberosin Produced from Elicited Kudzu (Pueraria lobata)

TL;DR

This study explores how a compound from kudzu, called tuberosin, affects estrogen receptors in different cell types, suggesting potential use in breast cancer treatment.

Contribution

The study reveals cell-type-specific modulation of estrogen receptor activity by tuberosin, a phytoalexin from kudzu.

Findings

Tuberosin acts as an antagonist or competitive inhibitor in ER-positive breast cancer cells.

Tuberosin shows dose-dependent agonist activity in HEK293 cells expressing ERα and ERβ.

Tuberosin alters ER-mediated gene expression and suppresses vascular network assembly in endothelial cells.

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.

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