SAT-236 In Vitro Estrogenicity of Pigeon Pea (Cajanus cajan (L.) Millsp.) Extracts and the Extracted Secondary Metabolites of Cajanol and Cajanin

Abstract Disclosure: E.L. Smith: None. T. Wiese: None. C.C. Williams: None. H. Kim: None. S. Boue: None. Cajanol and cajanin are secondary metabolites of the pigeon pea plant (Cajanus cajan (L.) Millsp.) that have been noted for potential pharmacological activity. Much of the literature documents the purported hypoglycemic, oxidative stressor, and P13K pathway inhibitory effects. Here, we propose that cajanol and cajanin may impact endocrine function by direct interaction with Estrogen receptor α (ERα). As such, it is feasible that these compounds may impact estrogen dependent proliferation, specifically in breast carcinoma cells. As such, this study aims to characterize the estrogenic/antiestrogenic effects of cajanol and cajanin utilizing computational, in vitro, and breast cancer cell models. Computational models suggest that both Cajanol and Cajanin interact in the canonical ligand binding pocket of ERα, similar to estradiol. Indeed, we observed a notable increase in ERE-luciferase activity in a T-47D based reporter cell line, supporting the concept that these compounds are estrogenic and may bind directly to ERα. This agonistic activity was associated with increased proliferation in ERα(+), estrogen sensitive MCF7-E3 cells. Using Monolith Microscale Thermophoresis and Spectral Shift technology, we demonstrated direct in vitro interaction of cajanin with ERα. Together, these studies support our contention that these phytochemical mediate pro-estrogenic activity through direct receptor interaction, and a solid rationale for the further exploration of their potential nutraceutical or endocrine disrupting effects. Presentation: Saturday, July 12, 2025