Neuroblastoma is a highly
malignant neoplasm found in young children. Although children with high-risk
neuroblastoma respond to
chemotherapy, relapses are common. On account of poor treatment outcome, new treatment strategies are constantly sought for
neuroblastoma.
Polyamine analogues are potentially novel substances for treatment of
neuroblastoma. In this study, we have treated two
neuroblastoma cell lines, SH-SY5Y and LA-N-1, with the
spermine analogue N1, N11-Diethylnorspermine (
DENSPM). SH-SY5Y was the most sensitive cell line, in which
DENSPM treatment resulted in an inhibition of cell proliferation and an induction of cell death. The cell death induced by
DENSPM treatment was apoptotic, as evidenced by cleavage of
procaspase 3 and induction of
caspase-3 activity. In contrast,
DENSPM treatment only resulted in a slight inhibition of cell proliferation in LA-N-1 cells. There were several possible causes for the lower sensitivity to
DENSPM treatment in the latter cell line when compared with SH-SY5Y cells.
DENSPM-induced
polyamine depletion was more extensive in SH-SY5Y cells than in LA-N-1 cells. This was partly because of a higher induction of the
polyamine catabolic
enzyme spermidine/
spermine N1-acetyltransferase in the cell line SH-SY5Y. The
DENSPM-induced
polyamine depletion was also caused by the inhibition of
ornithine decarboxylase. LA-N-1 cells contained a higher level of the prosurvival
protein survivin, which was further increased after
DENSPM treatment. In contrast,
DENSPM treatment resulted in a decreased
survivin level in SH-SY5Y cells.