Cytotoxicity of the polyamine oxidase inactivator MDL 72527 to cancer cells: Comparison with a saturated structural analogue
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- Published online on: December 1, 2005 https://doi.org/10.3892/ijo.27.6.1669
- Pages: 1669-1676
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Abstract
MDL 72527 (N1,N4-di-2,3-butadienyl-1,4-butanediamine) is a selective inactivator of polyamine oxidase with therapeutic potential. However, the development of lethal toxic effects due to prevention of spermine degradation is a considerable disadvantage of the compound. Since the cytotoxicity of MDL 72527 was postulated to be independent of its anti-polyamine oxidase activity, its cytotoxicity to cancer cells was compared with that of a close analogue that is devoid of structural features enabling mechanism-based inactivation of polyamine oxidase. N1,N4-di-n-butyl-1,4-butanediamine proved to be a cytotoxic agent of considerable potency, which induces mainly non-apoptotic cell death, whereas MDL 72527 causes under identical conditions both, apoptotic and non-apoptotic cell death. The sensitivity of cells to both compounds is presumably dependent of their glutathione content.