Apoptosis induction in human breast cancer MRK-nu-1 cells by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone)(MGBCP).

We have investigated the antiproliferative effects of a polyamine synthesis 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 contents in the cells decreased. Moreover, morphological changes indicating blebbing 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 number of characteristic oligonucleosome-sized fragments also increased as the concentration of MGBCP increased. The apoptotic effects of MGBCP were partially prevented by the addition of exogenous spermine. The results presented here suggest that, in addition to reducing the growth rate, MGBCP can induce apoptotic cell death in MRK-nu-1 human breast cancer cells by the reduction of intracellular concentrations of polyamines.