Cannabis sativa L. stem ethanol extract suppresses ERα-mediated endocrine disrupting effects induced by bisphenol A in a breast cancer cell line

초록

Cannabis sativa L. (hemp), a Cannabaceae family member, has been extensively studied for its diverse secondary metabolites with physiological activities. However, stems that lack detectable levels of the delta-9tetrahydrocannabinol have been understudied. Herein, we aimed to investigate the antagonistic effects using C. sativa L. stem ethanol extract (CSE) and its bioactive compounds on human ER alpha activity induced by exogenous estrogen, bisphenol A (BPA), through genomic and non-genomic pathways. CSE inhibited BPA-induced ER alpha transcriptional activation in VM7Luc4E2 cells and suppressed cell proliferation. Among the secondary metabolites in CSE, cyclopentane-1,2-dione (CPD), 4-vinylguaiacol (4-VG), and 4-([1E]-hydroxy-1-propenyl)-2methoxyphenol (4-HMP) exhibited antagonistic effects on ER alpha transcriptional activation and inhibited cell proliferation. Cell proliferation suppression was mediated by downregulation of p38 phosphorylation in the MAPK signaling pathway. CPD inhibited exogenous estrogen-induced activation of ER alpha without significant affecting the translocation of cytosolic ER alpha to the nucleus. In contrast, 4-VG and 4-HMP exerted antagonistic effect based on suppressing the nuclear translocation of cytosolic ER alpha. Collectively, the results showed that CSE suppressed ER alpha-mediated endocrine disruption induced by exogenous estrogen, suggesting its potential as a natural ingredient to reduce endocrine disruption from dietary sources.

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