Modulation of the reversibility of actinomycin D cytotoxicity in HeLa cells by verapamil.

Actinomycin D treatment (0.001-0.005 micrograms/ml; 0.5-24 h) induced a dose and time response shifting of nucleolar to nuclear fluorescence. In the presence of verapamil, cells were more responsive to actinomycin D. Translocation of protein B23 occurred with lower doses of actinomycin D and in shorter incubation times in the presence of verapamil. Short exposure (0.5 h) of HeLa cells to actinomycin D (0.05-0.25 micrograms/ml) induced 'reversible' translocation of protein B23 as well as 'reversible' inhibition of cell growth and RNA synthesis. Verapamil (5 microM) included in the cell culture after removal of actinomycin D inhibited the recoveries of cell growth, RNA synthesis as well as the corresponding relocalization of protein B23 from the nucleoplasm to nucleoli. These results indicate that verapamil can potentiate the antiproliferating activity of actinomycin D by inhibiting reversibility of its cytotoxicity and suggest clinical application.