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Drug Des Devel Ther. 2013 Jul 24;7:635-43. doi: 10.2147/DDDT.S49197. eCollection 2013.

Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis.

Author information

1
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.

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.

KEYWORDS:

apoptosis; prostate cancer; serine hydroxymethyltransferase

PMID:
23983455
PMCID:
PMC3749059
DOI:
10.2147/DDDT.S49197
[Indexed for MEDLINE]
Free PMC Article

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