APOPTOSIS INDUCTION IN HUMAN BREAST-CANCER MRK-NU-1 CELLS BY A POLYAMINE SYNTHESIS INHIBITOR, METHYLGLYOXAL HIS (CYCLOPENTYLAMIDINOHYDRAZONE) (MGBCP)

We have investigated the antiproliferative effects of a polyamine synt hesis inhibitor; methylglyoxal bis(cyclopentylamidinohydrazone) (MCBCP ), on human breast cancer MRK-nu-1 cells. MGBCP inhibited tumor growth of MRK-nu-1 cells in a dose-dependent manner as the polyamine content s in the cells decreased. Moreover, morphological changes indicating b lebbing and chromatin condensation were observed in the MGBCP-treated cells, and hypodiploid subpopulations containing apoptotic cells were clearly detected in the profile of flow cytometric analysis. The numbe r of characteristic oligonucleosome-sized fragments also increased as the concentration of MGBCP increased The apoptotic effects of MGBCP we re partially prevented by the addition of exogenous spermine. The resu lts presented here suggest that, in addition to reducing the growth ra te, MGBCP can induce apoptotic cell death in MRK-nu-1 human breast can cer-cells by the reduction of intracellular concentrations of polyamin es.