Suppression by herbimycin A of 12-O-tetradecanoylphorbol-13-acetate-induced dissociation of cells and morphological changes in cultured FL and MDCK cells

Human amnion membrane epithelial (FL) and Madin-Darby canine kidney (MDCK) cells formed colonies which consisted of tightly packed cells. A bundle of actin filaments in the cells at the edge of the colonies ran parallel to the outline of these cells. The cells were attached to the substratum by regions which were observed as black solid lines by interference-reflection microscopy. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 24 hr induced dissociation of and morphological changes in the cells in the colonies. TPA also disrupted the organization of the actin filaments and the attachment of cells to the substratum. Addition of herbimycin A for 24 hr inhibited the TPA-induced dissociation of the cells in colonies. Treatment with herbimycin A also inhibited TPA-induced modulation of the organization of actin filaments and of the adhesion of cells to the substratum. However, herbimycin A did not inhibit the rapid spreading of cells induced by TPA in the absence of serum. These results suggest that herbimycin A inhibits the dissociation of cells and the morphological changes induced by TPA through suppression of the disruption of a bundle of actin filaments and modulation of adhesion of cells to the substratum.