Multiple activities of a novel substance, dictyopyrone C isolated from Dictyostelium discoideum, in cellular growth and differentiation

We report that a novel substance named dictyopyrone C (DPC) has remarkable effects on growth and differentiation of Dictyostelium discoideum Ax-2 cells, in a dose-dependent manner. In the presence of 3-15 μM DPC, differentiation of starving Ax-2 (clone MS) cells was greatly enhanced in submerged culture, when vegetative MS cells were harvested at the mid-late-exponential growth phase (>3 × 10⁶ cells per ml) and starved. In contrast, DPC above 30 μM markedly impaired the progression of differentiation including cell aggregation, most of starved cells being round after 3-4 h of DPC application and then lysed during further incubation. In the presence of 30 μM DPC however, MS cells that had been harvested at the early exponential growth phase (<5 × 10⁵ cells per ml) and starved became neither round nor lysed and exhibited rather enhanced differentiation. Essentially the same results were obtained in cultures of starved cells on nonnutrient agar. With respect to the DPC effect on MS cells growing in axenic medium, cell lysis and growth inhibition by DPC at concentrations higher than 15 μM were realized in the mid-late-exponential-growth-phase cells (>3 × 10⁶ cells per ml) but not in the early-exponential-growth-phase cells (<5 × 10⁵ cells per ml). Moreover, analysis using synchronized MS cells has demonstrated that the DPC effect changes in a cell-cycle-dependent manner. In contrast to such unique DPC actions, the pyrone ring of DPC had no effects on growth and differentiation within the range of 3-120 μM tested. These findings strongly suggested the importance of the combined structure of the pyrone ring and the linear carbon chain in revelation of the DPC activities.