Abstract
Human promyelogenous leukaemic cells (HL-60) were treated with novel spermine analogue, (S)-N-1-(2-methyl-1-butyl)-N-11-ethyl-4,8-diazaundecane (IPENSpm), and the effects on growth and intracellular polyamine metabolism were measured. IPENSpm was cytotoxic to these cells at concentrations greater than 2.5 muM. It induced apoptosis in a caspase-dependent manner and its toxicity profile was comparable with etoposide, a well-known anti-tumour agent and inducer of apoptosis. IPENSpm decreased intracellular polyamine content as a result of changes in ornithine decarboxylase activity and increases in spermidine/ spermine N-1-acetyltransferase and polyamine export. Analysis showed spermine and spermidine as the major intracellular polyamines, while putrescine and acetyl-polyamines were the main export compounds. IPENSpm used the polyamine transporter system for uptake and its accumulation in cells was prevented by polyamine transport inhibitors. IPENSpm can be classified as a polyamine anti-metabolite and it may be a promising new lead compound in terms of treatment of some human cancers.
Original language | English |
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Pages (from-to) | 307-312 |
Number of pages | 5 |
Journal | Biochemical Journal |
Volume | 367 |
Issue number | Pt 1 |
DOIs | |
Publication status | Published - 2002 |
Keywords
- caspase
- etoposide
- spermine
- transport
- HUMAN CANCER-CELLS
- ORNITHINE DECARBOXYLASE
- BREAST-CANCER
- C-MYC
- DEATH
- GROWTH
- CATABOLISM
- EFFLUX
- BIOSYNTHESIS
- ACETYLATION