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

Polyamines are important intracellular mediators of cell proliferation in cancer cells. In this study, we evaluated whether methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a polyamine synthesis inhibitor, induces apoptosis 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 gastric epithelial cell line (RGM-1). The growth of gastric cancer cell lines was dose-dependently inhibited by MGBCP. Almost all the cells became apoptotic when they were cultured in the presence of 40 muM MGBCP for 5 days. Very high concentration (200 muM) of MGBCP was needed to completely inhibit the proliferation of RGM-1 cells. The cellular concentrations of the polyamines,spermidine and spermine were significantly reduced (50%) when the gastric cancer cells were cultured in the presence of MGBCP (80 muM) for 5 days. Putrescine remained unchanged. The reductions of both spermidine and spermine were mild in RGM-1 cells. DNA fragmentation and TUNEL studies demonstrated 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 MGBCP as an anti-cancer agent in gastric cancer.