A commercial formulation of glyphosate inhibits proliferation and differentiation to adipocytes and induces apoptosis in 3T3-L1 fibroblasts

• Published in: Toxicology in vitro 2012-09, Vol.26 (6), p.1007-1013
• Main Authors: Martini, Claudia N., Gabrielli, Matías, Vila, María del C.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; 3T3-L1 fibroblasts; Adipocytes - cytology; Animals; Apoptosis; Apoptosis - drug effects; Caspase 3 - metabolism; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Differentiation; Fibroblasts - cytology; Fibroblasts - drug effects; Glycine - analogs & derivatives; Glycine - toxicity; Glyphosate; Glyphosate formulation; Herbicides - toxicity; Mice; Proliferation
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2012.04.017

► A commercial glyphosate formulation inhibited proliferation of 3T3-L1 fibroblasts. ► Glyphosate formulation-induced apoptosis was confirmed by two different approaches. ► This formulation also inhibited 3T3-L1 fibroblasts differentiation to adipocytes. ► When formulation was removed proliferation and differentiation could be recovered. ► Precaution must be taken since glyphosate formulation may provoke cellular damage. Glyphosate-based herbicides are extensively used for weed control all over the world. Therefore, it is important to investigate the putative toxic effects of these formulations which include not only glyphosate itself but also surfactants that may also be toxic. 3T3-L1 fibroblasts are a useful tool to study adipocyte differentiation, this cell line can be induced to differentiate by addition of a differentiation mixture containing insulin, dexamethasone and 3-isobutyl-1-methylxanthine. We used this cell line to investigate the effect of a commercial formulation of glyphosate (GF) on proliferation, survival and differentiation. It was found that treatment of exponentially growing cells with GF for 48h inhibited proliferation in a dose-dependent manner. In addition, treatment with GF dilution 1:2000 during 24 or 48h inhibited proliferation and increased cell death, as evaluated by trypan blue-exclusion, in a time-dependent manner. We showed that treatment of 3T3-L1 fibroblasts with GF increased caspase-3 like activity and annexin-V positive cells as evaluated by flow cytometric analysis, which are both indicative of induction of apoptosis. It was also found that after the removal of GF, remaining cells were able to restore proliferation. On the other hand, GF treatment severely inhibited the differentiation of 3T3-L1 fibroblasts to adipocytes. According to our results, a glyphosate-based herbicide inhibits proliferation and differentiation in this mammalian cell line and induces apoptosis suggesting GF-mediated cellular damage. Thus, GF is a potential risk factor for human health and the environment.