Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents.
The safety, including the endocrine disruptive capability, of glyphosate-based herbicides (GBHs) is a matter of intense debate. We evaluated the estrogenic potential of glyphosate, commercial GBHs and polyethoxylated tallowamine adjuvants present as co-formulants in GBHs. Glyphosate (≥10,000 μg/L or 59 μM) promoted proliferation of estrogen-dependent MCF-7 human breast cancer cells. Glyphosate also increased the expression of an estrogen response element-luciferase reporter gene (ERE-luc) in T47D-KBluc cells, which was blocked by the estrogen antagonist ICI 182,780. Commercial GBH formulations or their adjuvants alone did not exhibit estrogenic effects in either assay. Transcriptomics analysis of MCF-7 cells treated with glyphosate revealed changes in gene expression reflective of hormone-induced cell proliferation but did not overlap with an ERα gene expression biomarker. Calculation of glyphosate binding energy to ERα predicts a weak and unstable interaction (-4.10 kcal mol-1) compared to estradiol (-25.79 kcal mol-1), which suggests that activation of this receptor by glyphosate is via a ligand-independent mechanism. Induction of ERE-luc expression by the PKA signalling activator IBMX shows that ERE-luc is responsive to ligand-independent activation, suggesting a possible mechanism of glyphosate-mediated activation. Our study reveals that glyphosate, but not other components present in GBHs, can activate ERα in vitro, albeit at relatively high concentrations.
['Mesnage|Robin|R|', 'Phedonos|Alexia|A|', 'Biserni|Martina|M|', 'Arno|Matthew|M|', 'Balu|Sucharitha|S|', 'Corton|J Christopher|JC|', 'Ugarte|Ricardo|R|', 'Antoniou|Michael N|MN|']
D001559:Benzhydryl Compounds D045744:Cell Line, Tumor D004305:Dose-Response Relationship, Drug D015536:Down-Regulation D004958:Estradiol D047628:Estrogen Receptor alpha D005786:Gene Expression Regulation D005998:Glycine D006540:Herbicides D006801:Humans D020411:Oligonucleotide Array Sequence Analysis D010636:Phenols D011092:Polyethylene Glycols D017423:Sequence Analysis, RNA D059467:Transcriptome D015854:Up-Regulation
Estrogen receptor Glyphosate Breast cancer Endocrine disrupting effects Pesticides