Morphologic and phenotypic changes of human neuroblastoma cells in culture induced by cytosine arabinoside.
The effects of cytosine-arabinoside (ARA-C) on the growth and phenotypic expression of a new human neuroblastoma (NB) cell line (GI-ME-N) have been extensively tested. Low doses of ARA-C allowing more than 90% cell viability induce morphological differentiation and growth inhibition. Differentiated cells were larger and flattened with elongated dendritic processes; such cells appeared within 48 h after a dose of ARA-C as low as 0.1 micrograms/ml (about 1000-fold lower than the conventional clinic dose). The new morphological aspect reached the maximum expression after 5-6 days of culture being independent from the addition of extra drug to the culture. A decrease in [3H]thymidine incorporation was also observed within 24 h and the cell growth was completely inhibited on the sixth day. Moreover, ARA-C strongly inhibited anchorage-independent growth in soft agar assay. Membrane immunofluorescence showed several dramatic changes in NB-specific antigen expression after 5 days of treatment with ARA-C. At the same time ARA-C also modulated cytoskeletal proteins and slightly increased catecholamine expression. These findings suggest that noncytotoxic doses of ARA-C do promote the differentiation of GI-ME-N neuroblastoma cells associated with reduced expression of the malignant phenotype.
Ponzoni
M
M
Pediatric Oncology Research Laboratory, G. Gaslini Children's Hospital, Genoa, Italy.
Lanciotti
M
M
Melodia
A
A
Casalaro
A
A
Cornaglia-Ferraris
P
P
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000032:analysis; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects; D007700:Kinetics; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D009638:Norepinephrine / Q000032:analysis; D014407:Tumor Cells, Cultured
D003598:Cytoskeletal Proteins; D003561:Cytarabine; D009638:Norepinephrine; D004837:Epinephrine