Context-Dependent\nEstrogenic Actions of (+)-Pisatin\nProduced in Elicited Green or Snow Pea (Pisum sativum)

Legumes are a predominant source of isoflavones, termed\nphytoestrogens,\nthat mimic 17β-estradiol (E2). Phytoalexins are inducible isoflavones\nproduced in plants subjected to environmental stressors (e.g., UV,\nheat, or fungi). This study investigated estrogenic activity of snow\nand green peas elicited with Aspergillus sojae. Elicited extracts increased estrogenic activity and proliferation\nof breast cancer cells (MCF-7 or T47D) in a dose-dependent manner\nbut exhibited antiestrogenic activity when combined with synthetic\nE2. HPLC analysis of elicited pea extracts identified (+)-pisatin\nas the primary phytoalexin, which was produced significantly (<i>p</i> < 0.0001) more in snow pea compared to green pea. RNA\nsequencing results suggested potential functional effects on endothelial\ncells and tissue vascularization. Indeed, (+)-pisatin enhanced metrics\nof network assembly and maturation in a microphysiological model of\nbulk tissue vasculogenesis. Thus, context-dependent functional effects\nof (+)-pisatin and pharmacologically similar phytoestrogens on the\nentire tissue microenvironment should be considered in preclinical\ninvestigation as potential therapeutic agents.