Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, MG, Brazil.
Laboratory of Nanobiotechnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia 38400-902, MG, Brazil.
Int J Mol Sci. 2023 Mar 28;24(7):6323. doi: 10.3390/ijms24076323.
Glyphosate (GLY) was developed in the early 1970s and has become the most used broad-spectrum herbicide in the world so far. Its main metabolite is aminomethylphosphonic acid (AMPA), and the accumulation of GLY and its derivative compounds raises some concerns regarding possible health outcomes. In this study, we aimed to evaluate the effects of GLY and AMPA on prostate cell lines by evaluating cell viability, proliferation, gene and protein expression, and cellular pathways involved in the response to oxidative stress. Our results indicated that GLY and AMPA reduced the cell viability of tumorigenic and non-tumorigenic prostate cell lines only at higher concentrations (10 mM GLY and 20 mM AMPA). In contrast, both compounds increased the clonogenicity of non-tumorigenic PNT2 cells, mainly at concentrations below the IC (5 mM GLY and 10 mM AMPA). Moreover, treatment of non-tumorigenic cells with low concentrations of GLY or AMPA for 48 h increased GSTM3 expression at both mRNA and protein levels. In contrast, the treatments decrease the GST activity and induced an increase in oxidative stress, mainly at lower concentrations. Therefore, both compounds can cause cellular damage even at lower concentrations in non-tumorigenic PNT2 cells, mainly affecting cell proliferation and oxidative stress.
草甘膦（GLY）于 20 世纪 70 年代初开发，至今已成为世界上使用最广泛的广谱除草剂。其主要代谢物是氨甲基膦酸（AMPA），GLY 及其衍生化合物的积累引起了人们对可能的健康结果的一些关注。在这项研究中，我们旨在通过评估细胞活力、增殖、基因和蛋白质表达以及参与氧化应激反应的细胞途径，来评估 GLY 和 AMPA 对前列腺细胞系的影响。我们的结果表明，GLY 和 AMPA 仅在较高浓度（GLY 为 10mM 和 AMPA 为 20mM）下才降低致瘤性和非致瘤性前列腺细胞系的细胞活力。相比之下，两种化合物均增加了非致瘤性 PNT2 细胞的集落形成能力，主要是在低于 IC（GLY 为 5mM 和 AMPA 为 10mM）的浓度下。此外，用低浓度 GLY 或 AMPA 处理非致瘤性细胞 48 小时会在 mRNA 和蛋白水平上增加 GSTM3 的表达。相比之下，这些处理会降低 GST 活性并诱导氧化应激增加，主要是在较低浓度下。因此，即使在非致瘤性 PNT2 细胞中，两种化合物在较低浓度下也可能导致细胞损伤，主要影响细胞增殖和氧化应激。
