INDUCTION OF APOPTOTIC CELL-DEATH IN 3 HUMAN OSTEOSARCOMA CELL-LINES BY A POLYAMINE SYNTHESIS INHIBITOR, METHYLGLYOXAL BIS(CYCLOPENTYLAMIDINOHYDRAZONE) (MGBCP)

Our previous experiments have shown that methylglyoxal bis(cyclopentyl amidinohydrazone) (MGBCP), a polyamine synthesis inhibitor, suppresses the growth of osteosarcoma cells repressing their intracellular polya mine levels, and that this inhibition of cell growth is only partially reversed by the addition of polyamines. In the present study, we foun d evidence indicating that the incomplete recovery of cell cell growth by the addition of polyamines to the polyamine-depleted cells was due to programmed cell death (apoptosis) induced by MGBCP. Morphological changes showing blebbing and chromatin condensation were observed in M GBCP-treated cells, and hypodiploid subpopulations containing apoptoti c cells were clearly visible in the profile of flow cytometric analysi s. Characteristic oligonucleosomal-sized fragments were increased as t he concentration of MGBCP was increased. The results presented here su ggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in three human osteosarcoma cell lines.