The role of P2 receptors for purines/pyrimidines is not well characterized in neuroblastoma, although a variety of purinergic mRNAs/proteins are expressed in these cells. Among these, the P2Y(6) receptor is the only subtype distinguished by UDP-specific activation. In this work, after over-expressing the P2Y(6) protein in human neuroblastoma SH-SY5Y cells, we find that UDP arrests cell cycle and induces apoptosis, by counteracting the pathological functioning of neuroblastoma in vitro. UDP also causes mitochondrial damage through diffusion of cytochrome c in the cytoplasm, and stimulates caspase-3,7,8 activities, with extensive over-expression of manganese superoxide dismutase. Our data establish the direct toxic role and anti-cancer activity of UDP in a neuroblastoma cell line, and identify the P2Y(6) receptor as a novel potential target in anti-tumoural therapies. This constitutes an advancement not only in the knowledge of purinergic signalling, but also in the biological and pathological aspects of neuroblastoma in vitro. (C) 2010 Elsevier Ltd. All rights reserved.

Apolloni, S., Finocchi, P., D'Agnano, I., Alloisio, S., Nobile, M., D'Ambrosi, N., et al. (2010). UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor. NEUROCHEMISTRY INTERNATIONAL, 56(5), 670-678 [10.1016/j.neuint.2010.02.003].

UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor

Apolloni S.;Nobile M.;D'Ambrosi N.;
2010

Abstract

The role of P2 receptors for purines/pyrimidines is not well characterized in neuroblastoma, although a variety of purinergic mRNAs/proteins are expressed in these cells. Among these, the P2Y(6) receptor is the only subtype distinguished by UDP-specific activation. In this work, after over-expressing the P2Y(6) protein in human neuroblastoma SH-SY5Y cells, we find that UDP arrests cell cycle and induces apoptosis, by counteracting the pathological functioning of neuroblastoma in vitro. UDP also causes mitochondrial damage through diffusion of cytochrome c in the cytoplasm, and stimulates caspase-3,7,8 activities, with extensive over-expression of manganese superoxide dismutase. Our data establish the direct toxic role and anti-cancer activity of UDP in a neuroblastoma cell line, and identify the P2Y(6) receptor as a novel potential target in anti-tumoural therapies. This constitutes an advancement not only in the knowledge of purinergic signalling, but also in the biological and pathological aspects of neuroblastoma in vitro. (C) 2010 Elsevier Ltd. All rights reserved.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
Extracellular ATP; Purinergic receptor; Cancer; Apoptosis; Caspase; Annexin A5; Apoptosis; Blotting, Western; Calcium; Caspase 3; Caspase 7; Cell Count; Cell Line, Tumor; Cell Survival; Cloning, Molecular; Electrophoresis, Polyacrylamide Gel; Humans; Microscopy, Fluorescence; Plasmids; RNA, Neoplasm; Receptors, Purinergic P2; Reverse Transcriptase Polymerase Chain Reaction; Uridine Diphosphate; Antineoplastic Agents; Cytostatic Agents
Apolloni, S., Finocchi, P., D'Agnano, I., Alloisio, S., Nobile, M., D'Ambrosi, N., et al. (2010). UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor. NEUROCHEMISTRY INTERNATIONAL, 56(5), 670-678 [10.1016/j.neuint.2010.02.003].
Apolloni, S; Finocchi, P; D'Agnano, I; Alloisio, S; Nobile, M; D'Ambrosi, N; Volonte, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/246858
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