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Apoptosis induced by the potential chemotherapeutic drug N1, N11-Diethylnorspermine in a neuroblastoma cell line.

Söderstjerna, Erika LU ; Holst, Martina LU ; Alm, Kersti LU and Oredsson, Stina LU (2010) In Anti-Cancer Drugs 21(10). p.917-926
Abstract
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 N, N-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... (More)
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 N, N-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 N-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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Anti-Cancer Drugs
volume
21
issue
10
pages
917 - 926
publisher
Rapid Communications
external identifiers
  • wos:000282599900005
  • pmid:20729713
  • scopus:78650055509
ISSN
0959-4973
DOI
10.1097/CAD.0b013e32833d1cae
language
English
LU publication?
yes
id
3fd98455-2a59-4163-95d3-c7fcc2adf210 (old id 1665099)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20729713?dopt=Abstract
date added to LUP
2010-09-03 11:04:38
date last changed
2018-05-29 09:20:20
@article{3fd98455-2a59-4163-95d3-c7fcc2adf210,
  abstract     = {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 N, N-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 N-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.},
  author       = {Söderstjerna, Erika and Holst, Martina and Alm, Kersti and Oredsson, Stina},
  issn         = {0959-4973},
  language     = {eng},
  number       = {10},
  pages        = {917--926},
  publisher    = {Rapid Communications},
  series       = {Anti-Cancer Drugs},
  title        = {Apoptosis induced by the potential chemotherapeutic drug N1, N11-Diethylnorspermine in a neuroblastoma cell line.},
  url          = {http://dx.doi.org/10.1097/CAD.0b013e32833d1cae},
  volume       = {21},
  year         = {2010},
}