Induction of spermidine/spermine N1-acetyltransferase in human breast carcinoma cells. A possible role for calcium.

Methylglyoxal bis(guanylhydrazone) (MGBG) a structural analogue of spermidine produced a dose-dependent induction of cytosolic spermidine/spermine N1-acetyltransferase (N1-SAT) in the human breast carcinoma cell line, T47-D. Intracellular accumulation of MGBG was found to be saturable and the drug produced characteristic effects on intracellular polyamines, decreasing spermidine and spermine content, with concomitant increases in putrescine levels. The MGBG-induced increase in N1-SAT activity was potentiated by both tetronasin, a calcium ionophore, and felodipine, a calcium channel blocking agent. Only tetronasin was an active inducer of the enzyme when used alone. Both drugs influenced intracellular MGBG content but in opposite directions: tetronasin increased MGBG content while felodipine decreased it. Therefore, the potentiation of N1-SAT induction is not simply the result of increased intracellular accumulation of MGBG but is more likely to be related to the concentration of intracellular free calcium in these cells.