Tuberosin,a novel phytoalexin that modulates estrogenic activity.

Authors: BELGODERE, JORGE - Tulane University; ELLIOT, JACK - Tulane University; BENZ, MEGAN - Tulane University; WILLIS, KPELI - Tulane University; ELLIOT, SETVEN - Tulane University; PONDER, ISAAC - Tulane University; MA, PENG - Tulane University; DIETRICH, SOPHIE - Tulane University; BUROW, MATTHEW - Tulane University; Boue, Stephen; CHENG, THOMAS - Tulane University; NGUYEN, KHOA - Tulane University; ZOU, BINGHAO - Tulane University; ANBALAGAN, MURAHDHARAN - Tulane University; ROWAN, BRIAN - Tulane University; NEWMAN, TOM - Tulane University; MONDRINOS, MARK - (NCE, CECR)networks Of Centres Of Exellence Of Canada, Centres Of Excellence For Commercilization A; SRIDHAR, JAYALAKSHMI - Xavier University; WIESE, THOMAS - Xavier University; HOANG, VAN - Tulane University; COLLINS-BUROW, BRIDGETTE - Tulane University; MARTIN, ELIZABETH - Tulane University; Abbas, Hamed

Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/9/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary: Kudzu, a plant native to many Asian countries, is considered an invasive species in North America, where it aggressively outcompetes other native flora, including mature trees, and potentially drives them to extinction through resource competition. Despite its invasive status, kudzu contains compounds with notable medicinal properties derived from its roots, stems, and leaves. In this study, we explored potential applications of these compounds in endocrine therapies for breast cancer by inducing stress in kudzu leaves using ultraviolet-C (UVC) irradiation or the fungal pathogen Myrothecium verrucaria (M. verrucaria) to stimulate the production of bioactive compounds. Stressed kudzu leaves significantly increased tuberosin production (p<0.0001), with UVC exposure producing a significantly higher yield than M. verrucaria (p<0.0001). Tuberosin treatment altered estrogenic activity in cells, acting as both agonists and antagonists depending on the cell type. In human embryonic kidney cells (HEK293) cells changes in estrogenic activity induced by tuberosin were both dose-dependent and receptor-specific (ER-a vs. ER-ß). In the presence of synthetic estrogen, the effects of tuberosin were antagonistic (blocked effects of estrogen). In ER-positive MCF-7 and T-47D-breast cancer cells tuberosin treatment did not significantly increase estrogenic activity; however, in combination with synthetic estrogen, tuberosin induced antagonistic effects. Further cell analyses showed an upregulation of estrogen receptor response genes, in addition to dose-dependent increases in cell proliferation. Taken together these studies provide deeper insight into the complex nature of tuberosin, as a potential endocrine therapy.

Technical Abstract: Kudzu, a plant native to many Asian countries, is considered an invasive species in North America, where it aggressively outcompetes other native flora, including mature trees, and potentially drives them to extinction through resource competition. Despite its invasive status, kudzu contains compounds with notable medicinal properties derived from its roots, stems, and leaves. In this study, we explored potential applications of these compounds in endocrine therapies for breast cancer by inducing stress in kudzu leaves using ultraviolet-C (UVC) irradiation or the fungal pathogen Myrothecium verrucaria (M. verrucaria) to stimulate the production of bioactive compounds. Stressed kudzu leaves significantly increased tuberosin production (p<0.0001), with UVC exposure producing a significantly higher yield than M. verrucaria (p<0.0001). Tuberosin treatment altered estrogenic activity in cells, acting as both agonists and antagonists depending on the cell type. In HEK293 cells, which lack endogenous expression of estrogen receptor (ER), changes in estrogenic activity induced by tuberosin were both dose-dependent and receptor-specific (ER-a vs. ER-ß). In the presence of synthetic estrogen, the effects of tuberosin were antagonistic, [add description of antagonistic effects]. In ER-positive MCF-7 and T-47D-breast cancer cells tuberosin treatment did not significantly increase estrogenic activity; however, in combination with synthetic estrogen, tuberosin induced antagonistic effects. Further transcriptomic analyses showed an upregulation of estrogen receptor response genes, in addition to dose-dependent increases in cell proliferation. Taken together these studies provide deeper insight into the complex nature of tuberosin, as a potential endocrine therapy.