title: Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis.
abstract: Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose) polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy.
authors: Departments of Structural and Cellular Biology and Orthopaedic Surgery, Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors: Qingli
authors: Q
authors: Li
authors: Mark J
authors: MJ
authors: Lambrechts
authors: Qiuyang
authors: Q
authors: Zhang
authors: Sen
authors: S
authors: Liu
authors: Dongxia
authors: D
authors: Ge
authors: Rutie
authors: R
authors: Yin
authors: Mingrong
authors: M
authors: Xi
authors: Zongbing
authors: Z
authors: You
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D007555:Isoxazoles; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D063065:Organophosphonates / Q000494:pharmacology*; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013777:Tetrazoles; D015854:Up-Regulation / Q000187:drug effects; D000097797:Glyphosate
chemical_list: D005998:Glycine; D007555:Isoxazoles; D063065:Organophosphonates; D013777:Tetrazoles; D000097797:Glyphosate; C418233:2-amino-3-(3-hydrox-5(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl)propionic acid
keywords: apoptosis; prostate cancer; serine hydroxymethyltransferase
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