Increased expression and activity of p75NTR are crucial events in azacitidine-induced cell death in prostate cancer

Gravina,Giovanni  Luca; Marampon,Francesco; Sanità,Patrizia; Mancini,Andrea; Colapietro,Alessandro; Scarsella,Luca; Jitariuc,Ana; Biordi,Leda; Ficorella,Corrado; Festuccia,Claudio

doi:10.3892/or.2016.4832

Increased expression and activity of p75NTR are crucial events in azacitidine-induced cell death in prostate cancer

Authors:
- Giovanni Luca Gravina
- Francesco Marampon
- Patrizia Sanità
- Andrea Mancini
- Alessandro Colapietro
- Luca Scarsella
- Ana Jitariuc
- Leda Biordi
- Corrado Ficorella
- Claudio Festuccia
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Affiliations: Department of Biotechnological and Applied Clinical Sciences, Division of Radiation Oncology, University of L'Aquila, I-67100 L'Aquila, Italy, Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, I-67100 L'Aquila, Italy, Department of Biotechnological and Applied Clinical Sciences, Laboratory of Molecular Oncology, University of L'Aquila, I-67100 L'Aquila, Italy, Department of Biotechnological and Applied Clinical Sciences, Division of Medical Oncology, University of L'Aquila, I-67100 L'Aquila, Italy
Published online on: May 23, 2016 https://doi.org/10.3892/or.2016.4832
Pages: 125-130

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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.

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