Context-Dependent Estrogenic Actions of (+)-Pisatin Produced in Elicited Green or Snow Pea (Pisum sativum)

Legumes are a predominant source of isoflavones, termed phytoestrogens, that mimic 17β-estradiol (E2). Phytoalexins are inducible isoflavones produced in plants subjected to environmental stressors (e.g., UV, heat, or fungi). This study investigated estrogenic activity of snow and green peas elicited with Aspergillus sojae. Elicited extracts increased estrogenic activity and proliferation of breast cancer cells (MCF-7 or T47D) in a dose-dependent manner but exhibited antiestrogenic activity when combined with synthetic E2. HPLC analysis of elicited pea extracts identified (+)-pisatin as the primary phytoalexin, which was produced significantly (p < 0.0001) more in snow pea compared to green pea. RNA sequencing results suggested potential functional effects on endothelial cells and tissue vascularization. Indeed, (+)-pisatin enhanced metrics of network assembly and maturation in a microphysiological model of bulk tissue vasculogenesis. Thus, context-dependent functional effects of (+)-pisatin and pharmacologically similar phytoestrogens on the entire tissue microenvironment should be considered in preclinical investigation as potential therapeutic agents.