Cytotoxic effects of the polyamine oxidase inactivator MDL 72527 to two human colon carcinoma cell lines SW480 and SW620 |
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Authors: | Duranton B Holl V Schneider Y Carnesecchi S Gossé F Raul F Seiler N |
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Institution: | (1) Laboratory of Nutritional Oncology, INSERM U392, Strasbourg, France;(2) Laboratory of Experimental Cancerology and Radiobiology, Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France |
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Abstract: | N
1,N
4-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527) was considered to be a selective inactivator of FAD-dependent tissue polyamine
oxidase. Recently MDL 72527 was reported to induce apoptosis in transformed hematopoietic cells through lysosomotropic effects.
Since it is the only useful inhibitor of polyamine oxidase available at present, the re-evaluation of its properties seemed
important. Human colon carcinoma-derived SW480 cells and their lymph node metastatic derivatives (SW620) were chosen for our
study because they differ in various aspects of polyamine metabolism but have similar polyamine oxidase activities. MDL 72527
inhibited cell growth in a concentration-dependent manner, depleted intracellular polyamine pools, and caused the accumulation
of N
1-acetyl derivatives of spermidine and spermine. SW620 cells were more sensitive to the drug than were SW480 cells. At 150
μmol/L MDL 72527, SW620 cells accumulated in S-phase of the cell cycle, showed decreased polyamine transport rate, and showed
no increase of polyamine N
1-acetyltransferase activity. In contrast, SW480 cells were not arrested in a particular phase of the cell cycle, showed enhanced
polyamine uptake, and showed a mild induction of acetyltransferase. The results suggest that MDL 72527 retains its value as
a selective tool in short-term experiments only at concentrations not exceeding those necessary for the inactivation of polyamine
oxidase. At concentrations above 50 μmol/L and at exposure times longer than 24 h, it may derange cell functions nonspecifically,
and thus blur the results of studies intended to elucidate polyamine oxidase functions.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | polyamine oxidase MDL 72527 cytotoxicity SW480 cells SW620 cells |
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