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

Savina Apolloni, Pamela Finocchi, Igea D'Agnano, Susanna Alloisio, Mario Nobile, Nadia D'Ambrosi, Cinzia Volonté

Research output: Contribution to journalArticle

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 P2Y6 receptor is the only subtype distinguished by UDP-specific activation. In this work, after over-expressing the P2Y6 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 P2Y6 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
Issue number5
DOIs
Publication statusPublished - Apr 2010

Fingerprint

Uridine Diphosphate
Cytostatic Agents
Neuroblastoma
Caspase 7
Purinergic Receptors
Pyrimidines
Poisons
Cell Cycle Checkpoints
Cytochromes c
Caspase 3
Superoxide Dismutase
Cytoplasm
Proteins
purinoceptor P2Y6
Apoptosis
Cell Line
Messenger RNA
Neoplasms

Keywords

  • Apoptosis
  • Cancer
  • Caspase
  • Extracellular ATP
  • Purinergic receptor

ASJC Scopus subject areas

  • Cell Biology
  • Cellular and Molecular Neuroscience

Cite this

Apolloni, S., Finocchi, P., D'Agnano, I., Alloisio, S., Nobile, M., D'Ambrosi, N., & Volonté, C. (2010). UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor. Neurochemistry International, 56(5), 670-678. https://doi.org/10.1016/j.neuint.2010.02.003

UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor. / Apolloni, Savina; Finocchi, Pamela; D'Agnano, Igea; Alloisio, Susanna; Nobile, Mario; D'Ambrosi, Nadia; Volonté, Cinzia.

In: Neurochemistry International, Vol. 56, No. 5, 04.2010, p. 670-678.

Research output: Contribution to journalArticle

Apolloni, S, Finocchi, P, D'Agnano, I, Alloisio, S, Nobile, M, D'Ambrosi, N & Volonté, C 2010, 'UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor', Neurochemistry International, vol. 56, no. 5, pp. 670-678. https://doi.org/10.1016/j.neuint.2010.02.003
Apolloni, Savina ; Finocchi, Pamela ; D'Agnano, Igea ; Alloisio, Susanna ; Nobile, Mario ; D'Ambrosi, Nadia ; Volonté, Cinzia. / UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor. In: Neurochemistry International. 2010 ; Vol. 56, No. 5. pp. 670-678.
@article{63d08a6904a44b46a9ab932a6945e4b2,
title = "UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor",
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 P2Y6 receptor is the only subtype distinguished by UDP-specific activation. In this work, after over-expressing the P2Y6 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 P2Y6 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.",
keywords = "Apoptosis, Cancer, Caspase, Extracellular ATP, Purinergic receptor",
author = "Savina Apolloni and Pamela Finocchi and Igea D'Agnano and Susanna Alloisio and Mario Nobile and Nadia D'Ambrosi and Cinzia Volont{\'e}",
year = "2010",
month = "4",
doi = "10.1016/j.neuint.2010.02.003",
language = "English",
volume = "56",
pages = "670--678",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor

AU - Apolloni, Savina

AU - Finocchi, Pamela

AU - D'Agnano, Igea

AU - Alloisio, Susanna

AU - Nobile, Mario

AU - D'Ambrosi, Nadia

AU - Volonté, Cinzia

PY - 2010/4

Y1 - 2010/4

N2 - 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 P2Y6 receptor is the only subtype distinguished by UDP-specific activation. In this work, after over-expressing the P2Y6 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 P2Y6 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.

AB - 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 P2Y6 receptor is the only subtype distinguished by UDP-specific activation. In this work, after over-expressing the P2Y6 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 P2Y6 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.

KW - Apoptosis

KW - Cancer

KW - Caspase

KW - Extracellular ATP

KW - Purinergic receptor

UR - http://www.scopus.com/inward/record.url?scp=77949571610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949571610&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2010.02.003

DO - 10.1016/j.neuint.2010.02.003

M3 - Article

C2 - 20144676

AN - SCOPUS:77949571610

VL - 56

SP - 670

EP - 678

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

IS - 5

ER -