title: 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.
authors.forename: Keshab R
authors.initials: KR
authors.lastname: Parajuli
authors.forename: Qiuyang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.forename: Zongbing
authors.initials: Z
authors.lastname: You
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007555:Isoxazoles; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013777:Tetrazoles
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; D007555:Isoxazoles; D063065:Organophosphonates; D013777:Tetrazoles; C013598:methoxyacetic acid; C418233:2-amino-3-(3-hydrox-5(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl)propionic acid
keywords: AMPA; MAA; apoptosis; cell death; prostate cancer cells