Differentiation state affects morphine induced cell regulation in neuroblastoma cultured cells.
Neuroblastoma (NB) is the most common extracranial solid cancer in childhood and the most common cancer in infancy. Our purpose was to investigate in vitro how cancer cell survival occurs in presence of morphine in undifferentiated and differentiated SHSY-5Y human neuroblastoma cultured cell line. Exposure of differentiated cells to morphine dose-dependently induced apoptosis in these cells through c-Jun N-terminal kinase (JNK)/caspase pathway. Otherwise, morphine induced activation for mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, caused positive regulation of cell survival in undifferentiated cells. Therefore, cell differentiation state bimodally affects the cellular regulation activity triggered by morphine in isolated cultured neuroblastoma cells raising concerns about the application of morphine to this type of cancer patients.
Department of Pharmacology, University of Siena, Italy.
Giovina
G
Fiore
Carla
C
Ghelardini
Giancarlo
G
Bruni
Massimo
M
Guarna
Enrica
E
Bianchi
D000701:Analgesics, Opioid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009020:Morphine / Q000494:pharmacology*; D009447:Neuroblastoma; D011518:Proto-Oncogene Proteins / Q000378:metabolism
D000701:Analgesics, Opioid; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D009020:Morphine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3
Cell differentiation; Cell survival; ERK; GAP43; GFAP; JNK; MAPK; Morphine; NF-M; NSE; Neuroblastoma cells; Neuron-Specific Enolase; PPAR; RA; Signaling pathway; anti-Growth-Associated Protein 43; c-Jun N-terminal kinase; extracellular signal-regulated kinase; glial fibrillary acidic protein; mitogen-activated protein kinase; morphine; morphine HCl; neurofilament M; peroxisome proliferator-activated receptors; retinoic acid; μ opioid receptor; μOR