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Putative morphogen, DIF, of Dictyostelium discoideum induces apoptosis in rat pancreatic AR42J cells

We have recently shown that differentiation‐inducing factor‐1 (DIF‐1) of Dictyostelium discoideum is capable of raising intracellular calcium concentration ([Ca2+]i) and suppressing cell proliferation of rat pancreatic AR42J cells in a dose‐dependent manner, and that DIF‐1 at a concentration of 40 μmol/L is toxic to the cells. In this study, we have further characterized the cytotoxic effect of DIF‐1 on AR42J cells and have analyzed the effect of DIF‐1 on [Ca2+]i. In the presence of 40 μmol/L DIF‐1, cells began to bleb after approximately 6 h, and most had died within 48 h. Biochemical analysis revealed that DNA fragmentation was accompanied by cell death. Monitoring the changes in [Ca2+]i induced by DIF‐1, it was found that cells were able to adapt to stimulation with DIF‐1 so that they did not respond to subsequent stimulation by DIF‐1. These results indicate that DIF‐1 induced apoptosis in AR42J cells probably via a cell signaling system.