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.
Santa Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, Italy. s.apolloni@hsantalucia.it <s.apolloni@hsantalucia.it>
Savina
S
Apolloni
Pamela
P
Finocchi
Igea
I
D'Agnano
Susanna
S
Alloisio
Mario
M
Nobile
Nadia
N
D'Ambrosi
Cinzia
C
Volonté
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