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Rapid caspase-dependent cell death in cultured human breast cancer cells induced by the polyamine analogue N-1,N-11-diethylnorspermine

Hegardt, Cecilia LU ; Johannsson, OT and Oredsson, Stina LU (2002) In European Journal of Biochemistry 269(3). p.1033-1039
Abstract
The spen-nine analogue N-1,N-11-diethylnorspermine (DENSPM) efficiently depletes the cellular pools of putrescine, spermidine and spermine by down-regulating the activity of the polyamine biosynthetic enzymes and up-regulating the activity of the catabolic enzyme spermidine/spermine N-1-acetyltransferase (SSAT). In the breast cancer cell line L56Br-Cl. treatment with 10 muM DENSPM induced SSAT activity 60 and 240-fold at 24 and 48 h after seeding. respectively, which resulted in polyamine depletion. Cell proliferation appeared to be totally inhibited and within 48 h of treatment, there was an extensive apoptotic response. Fifty percent of the cells were found in the sub-G(1) region, as determined by flow cytometry, and the presence of... (More)
The spen-nine analogue N-1,N-11-diethylnorspermine (DENSPM) efficiently depletes the cellular pools of putrescine, spermidine and spermine by down-regulating the activity of the polyamine biosynthetic enzymes and up-regulating the activity of the catabolic enzyme spermidine/spermine N-1-acetyltransferase (SSAT). In the breast cancer cell line L56Br-Cl. treatment with 10 muM DENSPM induced SSAT activity 60 and 240-fold at 24 and 48 h after seeding. respectively, which resulted in polyamine depletion. Cell proliferation appeared to be totally inhibited and within 48 h of treatment, there was an extensive apoptotic response. Fifty percent of the cells were found in the sub-G(1) region, as determined by flow cytometry, and the presence of apoptotic nuclei was morphologically assessed by fluorescence microscopy. Caspase-3 and caspase-9 activities were significantly elevated 24 h after seeding, At 48 h after seeding, caspase-3 and caspase-9 activities were further elevated and at this time point a significant activation of caspase-8 was also found. The DENSPM-induced cell death was dependent on the activation of the caspases as it was inhibited by the general caspase inhibitor Z-Val-Ala-Asp fluoromethyl ketone. The results are discussed in the fight of the L56Br-Cl cells containing mutated BRCA1 and p53, two genes involved in DNA repair. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
N-11-diethylnorspermine, N-1, DNA fragmentation, caspase, apoptosis, breast cancer cells
in
European Journal of Biochemistry
volume
269
issue
3
pages
1033 - 1039
publisher
Wiley-Blackwell
external identifiers
  • wos:000174059100033
  • pmid:11846806
  • scopus:0036186863
ISSN
0014-2956
DOI
10.1046/j.0014-2956.2001.02744.x
language
English
LU publication?
yes
id
7b5945e0-3051-4fc0-848e-b18f3e3cf32d (old id 342936)
date added to LUP
2016-04-01 17:00:37
date last changed
2022-01-28 23:44:43
@article{7b5945e0-3051-4fc0-848e-b18f3e3cf32d,
  abstract     = {{The spen-nine analogue N-1,N-11-diethylnorspermine (DENSPM) efficiently depletes the cellular pools of putrescine, spermidine and spermine by down-regulating the activity of the polyamine biosynthetic enzymes and up-regulating the activity of the catabolic enzyme spermidine/spermine N-1-acetyltransferase (SSAT). In the breast cancer cell line L56Br-Cl. treatment with 10 muM DENSPM induced SSAT activity 60 and 240-fold at 24 and 48 h after seeding. respectively, which resulted in polyamine depletion. Cell proliferation appeared to be totally inhibited and within 48 h of treatment, there was an extensive apoptotic response. Fifty percent of the cells were found in the sub-G(1) region, as determined by flow cytometry, and the presence of apoptotic nuclei was morphologically assessed by fluorescence microscopy. Caspase-3 and caspase-9 activities were significantly elevated 24 h after seeding, At 48 h after seeding, caspase-3 and caspase-9 activities were further elevated and at this time point a significant activation of caspase-8 was also found. The DENSPM-induced cell death was dependent on the activation of the caspases as it was inhibited by the general caspase inhibitor Z-Val-Ala-Asp fluoromethyl ketone. The results are discussed in the fight of the L56Br-Cl cells containing mutated BRCA1 and p53, two genes involved in DNA repair.}},
  author       = {{Hegardt, Cecilia and Johannsson, OT and Oredsson, Stina}},
  issn         = {{0014-2956}},
  keywords     = {{N-11-diethylnorspermine; N-1; DNA fragmentation; caspase; apoptosis; breast cancer cells}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{1033--1039}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{European Journal of Biochemistry}},
  title        = {{Rapid caspase-dependent cell death in cultured human breast cancer cells induced by the polyamine analogue N-1,N-11-diethylnorspermine}},
  url          = {{http://dx.doi.org/10.1046/j.0014-2956.2001.02744.x}},
  doi          = {{10.1046/j.0014-2956.2001.02744.x}},
  volume       = {{269}},
  year         = {{2002}},
}