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

Nadia D'Ambrosi, S Apolloni, P Finocchi, I D'Agnano, S Alloisio, M Nobile, C. Volonté

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)670-678
Number of pages9
JournalNeurochemistry International
Volume56
DOIs
Publication statusPublished - 2010

Keywords

  • Annexin A5
  • Antineoplastic Agents
  • Apoptosis
  • Blotting, Western
  • Calcium
  • Caspase 3
  • Caspase 7
  • Cell Count
  • Cell Line, Tumor
  • Cell Survival
  • Cloning, Molecular
  • Cytostatic Agents
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Microscopy, Fluorescence
  • Plasmids
  • RNA, Neoplasm
  • Receptors, Purinergic P2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uridine Diphosphate

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