UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor.
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.
Apolloni
Savina
S
Santa Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, Italy. s.apolloni@hsantalucia.it <s.apolloni@hsantalucia.it>
Finocchi
Pamela
P
D'Agnano
Igea
I
Alloisio
Susanna
S
Nobile
Mario
M
D'Ambrosi
Nadia
N
Volonté
Cinzia
C
D017304:Annexin A5; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D054697:Cytostatic Agents; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014530:Uridine Diphosphate / Q000494:pharmacology*
D017304:Annexin A5; D000970:Antineoplastic Agents; D054697:Cytostatic Agents; D012334:RNA, Neoplasm; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D014530:Uridine Diphosphate; D053148:Caspase 3; D053179:Caspase 7; D002118:Calcium