Effects of DIF-1, an anti-tumor agent isolated from Dictyostelium discoideum, on rat gastric mucosal RGM-1 and leptomeningeal cells

DIF-1 is a putative morphogen that induces stalk cell formation in the cell ular slime mold Dictyostelium discoideum, We have previously discovered tha t DIF-1 suppresses cell growth and induces cell differentiation in vitro in some tumor cells, and also that relatively low concentrations of DIF-1 pro mote retinoic acid-induced cell differentiation in the human myeloid leukem ia HL-60 cells. In this study, to verify cell biological and therapeutic po tential of DIF-1, we have examined whether and how DIF-1 affects normal mam malian cells in vitro, using rat leptomeningeal (RLM) cells and rat gastric mucosal RGM-1 cells. In growing phase of both cells, DIF-1 at 5-40 mu M su ppressed cell growth in a dose-dependent manner. High concentrations (15-40 mu M) of DIF-1 were toxic to the growing cells so that the cells showed un usual morphology, but many of them were still alive even at Day 3-4. Withdr awal of DIF-1 allowed the cells to grow. In confluent phase of the cells, D IF-1 at more than 15 mu M promoted medium acidification that resulted in ce ll death, but DIF-1 itself did not markedly affect cell viability for 3 day s. DIF-1 increased [Ca2+](i) in RLM cells but did not affect beta-trace sec retion (an index of cell function in RLM cells). A low concentration (5 mu M) of DIF-1 in combination with retinoic acid (0.1 mu M) showed no marked e ffects on cell growth, cell viability, cell morphology and beta-trace secre tion in RLM cells. The present results indicate that DIF-1 may be utilized as a tool for cell biology. Also, since these concentrations of DIF-1 kill some tumor cells within 2-3 days, the present results suggest that DIF-1 mi ght be utilized in the treatment of some sorts of cancer with a bearable de gree of side-effects.