Different effects of ribosome biogenesis inhibition on cell proliferation in retinoblastoma protein- and p53-deficient and proficient human osteosarcoma cell lines

Cell Prolif. 2007 Aug;40(4):532-49. doi: 10.1111/j.1365-2184.2007.00448.x.


Objectives: To evaluate the effects of rRNA synthesis inhibition on cell cycle progression and cell population growth according to the RB and p53 status.

Material and methods: RB- and p53-proficient U2OS cells and the RB- and p53-deficient SAOS-2 cells were used, rRNA transcription hindered by actinomycin D, and cell cycle analysed by flow cytometry.

Results: One hour of actinomycin D treatment induced in U2OS cells a block at the cell cycle checkpoints G(1)-S and G(2)-M, which was removed only after rRNA synthesis was resumed. rRNA synthesis inhibition did not influence cell cycle progression in SAOS-2 cells. No effect on cell cycle progression after actinomycin D-induced rRNA inhibition was also found in U2OS cells silenced for RB and p53 expression. A mild perturbation of cell cycle progression was observed in U2OS cells silenced for the expression of either RB or p53 alone. We also treated U2OS and SAOS-2 cells with actinomycin D for 1 h/day for 5 days. This treatment lightly reduced growth rate of the U2OS cell population, whereas cell population growth of SAOS-2 cells was completely inhibited. A marked reduction of ribosome content occurred in SAOS-2 cells after the long-term actinomycin D treatment, whereas no modification was observed in U2OS cells.

Conclusions: These results demonstrate that inhibition of ribosome biogenesis does not hinder cell cycle progression in RB- and p53-deficient cells. A daily-repeated transitory inhibition of ribosome biogenesis leads to a progressive reduction of ribosome content with the consequent extinction of cancer cell population lacking RB and p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Cycle* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dactinomycin / pharmacology
  • Humans
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA Interference
  • RNA, Ribosomal / biosynthesis*
  • Retinoblastoma Protein / antagonists & inhibitors
  • Retinoblastoma Protein / metabolism*
  • Ribosomes / metabolism
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / metabolism*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Nucleic Acid Synthesis Inhibitors
  • RNA, Ribosomal
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Dactinomycin