Induction of apoptosis in human gastric cancer cell lines by the polyaminesynthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP)

Polyamines are important intracellular mediators of cell proliferation in c ancer cells. In this study, we evaluated whether methylglyoxal bis(cyclopen tylamidinohydrazone) (MGBCP), a polyamine synthesis inhibitor, induces apop tosis and inhibits growth in gastric cancer cell lines (MKN-1, MKN-28, MKN- 45). For comparison, the same experiment was carried out in a normal rat ga stric epithelial cell line (RGM-1). The growth of gastric cancer cell lines was dose-dependently inhibited by MGBCP. Almost all the cells became apopt otic when they were cultured in the presence of 40 muM MGBCP for 5 days. Ve ry high concentration (200 muM) of MGBCP was needed to completely inhibit t he proliferation of RGM-1 cells. The cellular concentrations of the polyami nes,spermidine and spermine were significantly reduced (50%) when the gastr ic cancer cells were cultured in the presence of MGBCP (80 muM) for 5 days. Putrescine remained unchanged. The reductions of both spermidine and sperm ine were mild in RGM-1 cells. DNA fragmentation and TUNEL studies demonstra ted the occurrence of apoptosis in gastric cancer cell lines but not in RGM -1 cells. The results of this study suggest the potential usefulness of MGB CP as an anti-cancer agent in gastric cancer.