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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

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Author

Summary, in English

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.

Publishing year

2002

Language

English

Pages

1033-1039

Publication/Series

European Journal of Biochemistry

Volume

269

Issue

3

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cancer and Oncology

Keywords

  • N-11-diethylnorspermine
  • N-1
  • DNA fragmentation
  • caspase
  • apoptosis
  • breast cancer cells

Status

Published

ISBN/ISSN/Other

  • ISSN: 0014-2956