Morphological Transformation of Chinese Hamster Cells by Acylpeptides, Inhibitors of CAMP Phosphodiesterase, Produced by Bacillus Subtilis

Treatment of Chinese hamster ovary cells in vitro with acylpeptide, an inhibitor of adenosine 3':5'-cyclic monophosphate (cAMP) phosphodiesterase, produced by Bacillus subtilis C-756 converts the culture from one of randomly oriented, epithelial-like cells to one of elongated, fibroblast-like cells. This transformation is similar to the effect of N6,O2'-dibutyryl adenosine 3':5'-cyclic monophosphate (dibutyryl cAMP), but is manifested at a lower concentration of the inhibitor than with dibutyryl cAMP. The intracellular level of cAMP in the cells grown with the inhibitor is 3-4-fold higher than the level without the inhibitor. The transformation is reversible and, when reversed, the level of cAMP simultaneously decreases to the level without the inhibitor. The acylpeptide has cytolytic activity as well as inhibitory activity and the former activity is prevented by the addition of serum.