Aminomethylphosphonic Acid and Methoxyacetic Acid Induce Apoptosis in Prostate Cancer Cells

Abstract

Aminomethylphosphonic acid (AMPA) and its parent compound herbicide glyphosate are analogs to glycine, which have been reported to inhibit proliferation and promote apoptosis of cancer cells, but not normal cells. Methoxyacetic acid (MAA) is the active metabolite of ester phthalates widely used in industry as gelling, viscosity and stabilizer; its exposure is associated with developmental and reproductive toxicities in both rodents and humans. MAA has been reported to suppress prostate cancer cell growth by inducing growth arrest and apoptosis. However, it is unknown whether AMPA and MAA can inhibit cancer cell growth. In this study, we found that AMPA and MAA inhibited cell growth in prostate cancer cell lines (LNCaP, C4-2B, PC-3 and DU-145) through induction of apoptosis and cell cycle arrest at the G1 phase. Importantly, the AMPA-induced apoptosis was potentiated with the addition of MAA, which was due to downregulation of the anti-apoptotic gene baculoviral inhibitor of apoptosis protein repeat containing 2 (BIRC2), leading to activation of caspases 7 and 3. These results demonstrate that the combination of AMPA and MAA can promote the apoptosis of prostate cancer cells, suggesting that they can be used as potential therapeutic drugs in the treatment of prostate cancer.

Biofunctionalization of Textile Materials.1. Biofunctionalization of Poly(Propylene) (PP) Nonwovens Fabrics by Alafosfalin

“…Aminophosphonate compounds of special biological importance are presented in Table 2. [18,[29][30][31][32][33] β-Ala P (β-phosphono-alanine , 2-AEP, ciliatine)…”

“…The most widespread, first AA P isolated in natural sources [18,[34][35][36] Primary degradation product of glyphosate, inhibitor of prostate cancer cell growth in vitro, phytotoxin [18,[29][30][31][32][33] Coatings 2019, 9, 412 3 of 12 β-Ala P (β-phosphono-alanine, 2-AEP, ciliatine)…”

Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

“…How AMPA exerts its function has been shown in our previous in-vitro studies [ 9 , 10 ]. We demonstrated previously that AMPA up-regulated p53 and p21 as well as procaspase 9, activated caspase 3, and down-regulated cyclin D3 in C4-2B cells [ 9 ].…”

“…We demonstrated previously that AMPA up-regulated p53 and p21 as well as procaspase 9, activated caspase 3, and down-regulated cyclin D3 in C4-2B cells [ 9 ]. AMPA and particularly AMPA in combination with methoxyacetic acid down-regulated BIRC2 expression in PC-3 cells [ 10 ]. Therefore, we assessed the expression levels of the aforementioned genes in the tumors.…”

“…AMPA and glyphosate are analogs of glycine, which can inhibit the enzyme activities of SHMT [ 8 ]. We have previously shown that glyphosate and AMPA can inhibit proliferation and promote apoptosis in human prostate cancer cells, but not in normal cells in vitro [ 9 , 10 ]. In the present study, our objective was to determine if AMPA could inhibit prostate cancer growth and metastasis in vivo .…”