International Journal of Oncology 2005-12-01

Cytotoxicity of the polyamine oxidase inactivator MDL 72527 to cancer cells: comparison with a saturated structural analogue.

Nikolaus Seiler, Jacques Renault, Francine Gossé, Stamatiki Roussi, Francis Raul

Index: Int. J. Oncol. 27(6) , 1669-76, (2005)

Full Text: HTML

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.