Differentiation state affects morphine induced cell regulation in neuroblastoma cultured cells

• A higher number of live cells was observed in undifferentiated neuroblastoma cells incubated with morphine.
• The number of live cells was decreased in differentiated neuroblastoma cells incubated with morphine.
• Apoptosis was induced in neuroblastoma differentiated cells exposed to morphine through JNK/caspase pathway.
• Positive regulation of cell survival was induced in neuroblastoma undifferentiated cells by morphine through MAPK/ERK pathway.
• Cell differentiation state bimodally affects the cellular regulation activity in presence of morphine.

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.