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 acidification that resulted in cell death, but DIF-1 itself did not markedly affect cell viability for 3 days. DIF-1 increased [Ca2+], in RLM cells but did not affect β-trace secretion (an index of cell function in RLM cells). A low concentration (5 μM) of DIF-1 in combination with retinoic acid (0.1 μM) showed no marked effects on cell growth, cell viability, cell morphology and β-trace secretion 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 might be utilized in the treatment of some sorts of cancer with a bearable degree of side-effects.