N1,N4-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 N1-acetyl derivatives of
spermidine and
spermine. SW620 cells were more sensitive to the
drug than were SW480 cells. At 150 micromol/L
MDL 72527, SW620 cells accumulated in S-phase of the cell cycle, showed decreased
polyamine transport rate, and showed no increase of
polyamine N1-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 micromol/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.