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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

Författare:
Publiceringsår: 2002
Språk: Engelska
Sidor: 1033-1039
Publikation/Tidskrift/Serie: EUROPEAN JOURNAL OF BIOCHEMISTRY
Volym: 269
Nummer: 3
Dokumenttyp: Artikel
Förlag: BLACKWELL PUBLISHING LTD

Sammanfattning

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.

Disputation

Nyckelord

  • Biology and Life Sciences
  • Medicine and Health Sciences
  • N-11-diethylnorspermine
  • N-1
  • DNA fragmentation
  • caspase
  • apoptosis
  • breast cancer cells

Övrigt

Published
Yes
  • ISSN: 0014-2956

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