Cytotoxicity of the polyamine oxidase inactivator MDL 72527 to cancer cells: comparison with a saturated structural analogue.
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.
Seiler
Nikolaus
N
Laboratory of Nutritional Cancer Prevention, ULP-EA3430 Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), 1 place de l'hopital, 67091 Strasbourg Cedex, France. nikolaus.seiler@ircad.u-strasbg.fr
Renault
Jacques
J
Gossé
Francine
F
Roussi
Stamatiki
S
Raul
Francis
F
D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D011073:Polyamines; C044445:MDL 72527; D006861:Hydrogen Peroxide; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011700:Putrescine