Effects of DIF-1, an Anti-Tumor Agent Isolated from Dictyostelium discoideum, on Rat Gastric Mucosal RGM-1 and Leptomeningeal Cells

Abstract DIF-1 is a putative morphogen that induces stalk cell formation in the cellular slime mold Dictyostelium discoideum. We have previously discovered that DIF-1 suppresses cell growth and induces cell differentiation in vitro in some tumor cells, and also that relatively low concentrations of DIF-1 promote retinoic acid-induced cell differentiation in the human myeloid leukemia HL-60 cells. In this study, to verify cell biological and therapeutic potential of DIF-1, we have examined whether and how DIF-1 affects normal mammalian 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 μM suppressed cell growth in a dose-dependent manner. High concentrations (15–40 μM) of DIF-1 were toxic to the growing cells so that the cells showed unusual morphology, but many of them were still alive even at Day 3–4. Withdrawal of DIF-1 allowed the cells to grow. In confluent phase of the cells, DIF-1 at more than 15 μM promoted medium ...