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

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 . 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 ( < 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.