title: Increased expression and activity of p75NTR are crucial events in azacitidine-induced cell death in prostate cancer.
abstract: The high affinity nerve growth factor (NGF) NGF receptor, p75NTR, is a member of the tumor necrosis factor (TNF) receptor superfamily that shares a conserved intracellular death domain capable of inducing apoptosis and suppressing growth in prostate epithelial cells. Expression of this receptor is lost as prostate cancer progresses and is minimal in established prostate cancer cell lines. We aimed to verify the role of p75NTR in the azacitidine-mediated antitumor effects on 22Rv1 and PC3 androgen-independent prostate cancer cells. In the present study, we reported that the antiproliferative and pro-apoptotic effects of 5-azacytidine (azacitidine) were more marked in the presence of physiological concentrations of NGF and were reduced when a blocking p75NTR antibody or the selective p75NTR inhibitor, Ro 08-2750, were used. Azacitidine increased the expression of p75NTR without interfering with the expression of the low affinity NGF receptor TrkA and induced caspase 9-dependent caspase 3 activity. Taken together, our results suggest that the NGF network could be a candidate for future pharmacological manipulation in aggressive prostate cancer.
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Division of Radiation Oncology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Gravina
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Division of Radiation Oncology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marampon
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sanità
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mancini
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Colapietro
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Scarsella
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Ana
authors.initials: A
authors.lastname: Jitariuc
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Laboratory of Molecular Oncology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Leda
authors.initials: L
authors.lastname: Biordi
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Division of Medical Oncology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Ficorella
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, I-67100 L'Aquila, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Festuccia
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005415:Flavins; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011621:Pteridines / Q000494:pharmacology; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous
chemical_list: C412503:2,3,4,10-tetrahydro-7,10-dimethyl-2,4-dioxobenzo(g)pteridine; D000964:Antimetabolites, Antineoplastic; D005415:Flavins; C484065:NGFR protein, human; C000611485:NTRK1 protein, human; D009419:Nerve Tissue Proteins; D011621:Pteridines; D017475:Receptors, Nerve Growth Factor; D020917:Receptor, trkA; D053148:Caspase 3; D053453:Caspase 9; D001374:Azacitidine