Cell cycle phase-dependent cytotoxicity of actinomycin D in HeLa cells

Ming Hsiu Wu, Yat Ming Yung

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The effects of brief actinomycin D treatment (0.1 μg/ml, 0.5 h) on inhibition of cell growth and colony formation were studied in synchronized HeLa cells. Cells in late S and G2phases were found to be maximally sensitive to inhibition of cell growth and colony formation after short exposure to actinomycin D. Cells in G1and early S phases were less responsive to brief actinomycin D treatment; although there was a slowdown of cell growth between 24 and 48 h after removal of actinomycin D, recovery of cell growth was observed late (> 48 h) after drug removal. Cells in mitosis were maximally resistant to brief actinomycin D treatment, and continued to grow as did the control cells without drug. The effects of actinomycin D on inhibition of cell growth and colony formation were abolished by novobiocin but not by aphidicolin present during a brief actinomycin D treatment of cells at various cell cycle stages. Our results suggest that the effect of actinomycin D is cell cycle phase-dependent and may be involved in the action of topoisomerase II. Furthermore, actinomycin D at a low dose (0.1 μg/ml, 0.5 h) induced a slight G1block while a brief exposure to high dose actinomycin D (1.0 μg/ml, 0.5 h) caused a slowdown in the rate of cell progression through S and G2/M phases. Similar S and G2/M phase block was seen in cells that had been briefly treated with actinomycin D (0.1 μg/ml; 0.5 h) during late S and G2phases.
Original languageEnglish
Pages (from-to)203-212
Number of pages10
JournalEuropean Journal of Pharmacology: Environmental Toxicology and
Issue number2-3
Publication statusPublished - 4 Apr 1994
Externally publishedYes


  • Actinomycin D
  • Cell cycle
  • Cytotoxicity
  • Phase dependency

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Pollution

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