Journal or Publishing Institution: Food and Chemical Toxicology
Study: https://www.sciencedirect.com/science/article/pii/S0278691518303880
Author(s): Sritana, N., Suriyo, T., Kanitwithayanun, J., Somgvasin, B.H., Thiantanawat, A. and Satayavivad, J.
Article Type: Peer Reviewed Study
Record ID: 2200
Abstract: Previous studies showed that glyphosate stimulates breast cancer cell growth via estrogen receptors. The present study investigated the effect of glyphosate on the estrogen signaling pathway involved in the induction of cholangiocarcinoma (CCA) cell growth. HuCCA-1, RMCCA-1 and MMNK-1 were chosen for comparison. The effects of glyphosate on cell growth, cell cycle and molecular signaling pathways were measured. The results showed that HuCCA-1 cells expressed estrogen receptor alpha (ERα), while ERα was not detected in RMCCA-1 and MMNK-1 cells. ERα was mostly expressed in cytoplasmic compartment of HuCCA-1 cells. Estradiol (E2) (10−11-10−5 M) induced cell proliferation in HuCCA-1 but not in RMCCA-1 and MMNK-1 cells. Glyphosate at the same concentration range also induced HuCCA-1 cell proliferation. The S phase of the cell cycle, and protein levels of the cyclin family were significantly increased after treatment of glyphosate or E2. Both compounds also induced the expression of proliferative signaling–related proteins including ERα, VEGFR2, pERK, PI3K(p85), and PCNA. These effects of glyphosate and E2 were abolished by the ER antagonist, 4-hydroxytamoxifen and U0126, a MEK inhibitor. The data from this study indicate that glyphosate can induce cell growth in ERα positive CCA cells through non-genomic estrogen receptor/ERK1/2 signaling pathway.
Keywords: Estrogen Receptor, antagonists, breast neoplasms, cell growth, cell proliferation, cyclins, estradiol, estrogen receptors, glyphosate, interphase, neoplasm cells, phosphatidylinositol 3-kinase, proliferating cell nuclear antigen, protein content, signal transduction, toxicology, vascular endothelial growth factor receptor-2, Cell Line, Tumor Cell Line, Cholangiocarcinoma, Estrogen Receptor alpha, Glycine, Herbicides, Humans, MAP Kinase Signaling System, Metabolism, Pathology, Drug Effects, Analogs & Derivatives, Toxicity, Drug Effects
Citation: Sritana, N., Suriyo, T., Kanitwithayanun, J., Somgvasin, B.H., Thiantanawat, A. and Satayavivad, J., 2018. Glyphosate induces growth of estrogen receptor alpha positive cholangiocarcinoma cells via non-genomic estrogen receptor/ERK1/2 signaling pathway. Food and Chemical Toxicology, 118, pp. 595-607.
