title: Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model.
abstract: Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer.
authors: Departments of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA.
authors: Keshab Raj
authors: KR
authors: Parajuli
authors: Departments of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA.
authors: Qiuyang
authors: Q
authors: Zhang
authors: Departments of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA.
authors: Sen
authors: S
authors: Liu
authors: Departments of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA.|Department of Orthopaedic Surgery, Tulane University, New Orleans, Louisiana 70112, USA.|Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane University, New Orleans, Louisiana 70112, USA.|Tulane Center for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, Louisiana 70112, USA.|Tulane Center for Aging, Tulane University, New Orleans, Louisiana 70112, USA.
authors: Zongbing
authors: Z
authors: You
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D007555:Isoxazoles; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D063065:Organophosphonates / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013777:Tetrazoles; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C530105:Ccnd1 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D007555:Isoxazoles; D063065:Organophosphonates; D013777:Tetrazoles; D019938:Cyclin D1; C494834:Birc2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D053148:Caspase 3; C418233:2-amino-3-(3-hydrox-5(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl)propionic acid
keywords: aminomethylphosphonic acid; glyphosate; metastasis; orthotopic xenograft mouse model; prostate cancer