Context-dependent estrogenic actions of (+)-pisatin produced in elicited green or snow pea (Pisum Sativum).

Authors: BELGODERE, JORGE - Tulane University; BENZ, MEGAN - Tulane University; KPELI, WILLS - Tulane University; ELLIOT, JACK - Tulane University; ELLIOT, STEVEN - Tulane University; NORTH, JACK - Tulane University; PONDER, ISAAC - Tulane University; MA, PENG - Tulane University; DIETRICH, SOPHIE - Tulane University; CHENG, THOMAS - Tulane University; NGUYEN, KHOA - Tulane University; TILGHMAN, SYREETA - Florida A & M University; MCLACHLAN, JOHN - Tulane University; ZOU, BINGHAO - Tulane University; ANBALAGAN, MURALIDHARAN - Tulane University; ROWAN, B - Tulane University; MONDRINOS, MARK - Tulane University; WIESE, THOMAS - Xavier University; HOANG, VAN - Tulane University; COLLINS-BUROW, B - Tulane University; MARTIN, ELIZABETH - Tulane University; BUROW, MATTHEW - Tulane University; Boue, Stephen

Submitted to: Journal of Agriculture and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/27/2024
Publication Date: 12/12/2024
Citation: Boue, S.M., Burow, M., Wiese, T., Elliot, S., Martin, E., Belgodere, J., Benz, M., Kpeli, W., Elliot, J., North, J., Ponder, I., Ma, P., Dietrich, S., Cheng, T., Nguyen, K., Tilghman, S., Mclachlan, J., Zou, B., Anbalagan, M., Rowan, B.G., Mondrinos, M., Barnes, V., Collins-Burow, B.M. 2024. Context-dependent estrogenic actions of (+)-pisatin produced in elicited green or snow pea (Pisum Sativum).. Journal of Agriculture and Food Chemistry. https://doi.org/10.1021/acs.jafc.4c06409.
DOI: https://doi.org/10.1021/acs.jafc.4c06409

Interpretive Summary: Legumes are the predominant source of phytoestrogenic isoflavones mimicing the estradiol hormone. Legume phytoalexins are produced under conditions of stress including insect damage, wounding, or application of elicitors. The estrogenic and antiestrogenic activities of methanolic extracts obtained from snow peas treated with the fungus Aspergillus sojae were compared with untreated controls in several cell based assays. A. sojae-treated snow pea extracts displayed both estrogenic and antiestrogenic activities. Analysis of elicitor-treated snow pea extracts showed that A. sojae treatments induced production of one phytoalexin, pisatin, at a maximal of 1147 µg/g. In breast cancer cells adpated to measure estrogen response, pisatin displayed low estrogenic activity, however in a different assay pisatin stimulated breast cancer cell proliferation showing mild agonist activity. Additionally, pisatin exhibited antiestrogenic activity in an breast cancer cell colony survival assay. This work provides evidence that the A. sojae-treated snow pea extracts and the phytoalexin pisatin possess estrogenic and antiestrogenic activities.

Technical Abstract: Legumes are the predominant source of phytoestrogenic isoflavones mimicing the 17beta-estradiol (E2) hormone. Legume phytoalexins are produced under conditions of stress including insect damage, wounding, or application of elicitors. The estrogenic and antiestrogenic activities of methanolic extracts obtained from snow peas treated with the fungus Aspergillus sojae were compared with untreated controls using an estrogen responsive element-based (ERE) luciferase reporter assay. A. sojae-treated snow pea extracts displayed both estrogenic and antiestrogenic activities. Analysis of elicitor-treated snow pea extracts showed that A. sojae treatments induced production of one phytoalexin, pisatin, at a maximal of 1147 µg/g. Pisatin was isolated from A. sojae-treated snow pea extracts and analyzed for estrogenic activity using ER- alpha nd ER- beta binding, ERE luciferase assays in MCF-7 and HEK 293 cells, and MCF-7 cell proliferation. Pisatin showed low ER binding affinity with relatively higher binding affinity to ER-alpha. In an ERE luciferase assay in MCF-7 cells, pisatin displayed low ER transactivation, however pisatin stimulated MCF-7 cell proliferation with agonist activity between 0.1-10 µM. Pisatin exhibited lower estrogenic activity in a reporter gene assay with slightly higher ER-beta transactivation. Additionally, pisatin exhibited antiestrogenic activity in an MCF-7 colonial survival assay. This work provides evidence that the A. sojae-treated snow pea extracts and the phytoalexin pisatin possess estrogenic and antiestrogenic activities.