Abstract
Glyphosate is a broad-spectrum herbicide that is used worldwide. It represents a potential harm to surface water, and when commercially mixed with surfactants, its uptake is greatly magnified. The most well-known glyphosate-based product is Roundup. This herbicide is potentially an endocrine disruptor and many studies have shown the cytotoxicity potential of glyphosate-based herbicides. In breast cancer (BC) cell lines it has been demonstrated that glyphosate can induce cellular proliferation via estrogen receptors. Therefore, we aimed to identify gene expression changes in ER+ and ER- BC cell lines treated with Roundup and AMPA, to address changes in canonical pathways that would be related or not with the ER pathway, which we believe could interfere with cell proliferation. Using the Human Transcriptome Arrays 2.0, we identified gene expression changes in MCF-7 and MDA-MB-468 exposed to low concentrations and short exposure time to Roundup Original and AMPA. The results showed that at low concentration (0.05% Roundup) and short exposure (48h), both cell lines suffered deregulation of 11 canonical pathways, the most important being cell cycle and DNA damage repair pathways. Enrichment analysis showed similar results, except that MDA-MB-468 altered mainly metabolic processes. In contrast, 48h 10mM AMPA showed fewer differentially expressed genes, but also mainly related with metabolic processes. Our findings suggest that Roundup affects survival due to cell cycle deregulation and metabolism changes that may alter mitochondrial oxygen consumption, increase ROS levels, induce hypoxia, damage DNA repair, cause mutation accumulation and ultimately cell death. To our knowledge, this is the first study to analyze the effects of Roundup and AMPA on gene expression in triple negative BC cells. Therefore, we conclude that both compounds can cause cellular damage at low doses in a relatively short period of time in these two models, mainly affecting cell cycle and DNA repair.
Highlights
Glyphosate (N-(phosphonomethyl) glycine) is a broad-spectrum herbicide used worldwide in agriculture and forestry for weed control, representing a potential harm to surface water, ground waters and sediments [1,2,3,4,5,6]
Similar responses were found for MDA-MB-468, in which the 3 hour-treatment was more toxic than all other time points for all concentrations
Our aim was to show gene expression changes in estrogen receptor (ER)+ breast cancer (BC) cell line (MCF7) and in a triple negative BC cell line (MDA-MB-468) exposed to Roundup and aminomethylphosphonic acid (AMPA) to understand if the effect of these chemicals are dependent on cell ER positivity
Summary
Glyphosate (N-(phosphonomethyl) glycine) is a broad-spectrum herbicide used worldwide in agriculture and forestry for weed control, representing a potential harm to surface water, ground waters and sediments [1,2,3,4,5,6]. It has been commercialized since 1974, as GlyphosateBased Herbicides (GBHs). The shikimate pathway only exists in plants, bacteria and some fungi, which may explain the reported low toxicity in mammals (LD50 >4g/kg in humans). Glyphosate has been the most successful herbicide in history [4,5]
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