Inhibition of Retinoblastoma Cell Growth by CEP1347 Through Activation of the P53 Pathway

Anticancer Res. 2020 Sep;40(9):4961-4968. doi: 10.21873/anticanres.14499.


Background/aim: Despite advances in treatment modalities, the visual prognosis of retinoblastoma still remains unsatisfactory, underscoring the need to develop novel therapeutic approaches.

Materials and methods: The effect on the growth of six human retinoblastoma cell lines and a normal human fibroblast cell line of CEP1347, a small-molecule kinase inhibitor originally developed for the treatment of Parkinson's disease and therefore with a known safety profile in humans, was examined. The role of the P53 pathway in CEP1347-induced growth inhibition was also investigated.

Results: CEP1347 selectively inhibited the growth of retinoblastoma cell lines expressing murine double minute 4 (MDM4), a P53 inhibitor. Furthermore, CEP1347 reduced the expression of MDM4 and activated the P53 pathway in MDM4-expressing retinoblastoma cells, which was required for the inhibition of their growth by CEP1347.

Conclusion: We propose CEP1347 as a promising candidate for the treatment of retinoblastomas, where functional inactivation of P53 as a result of MDM4 activation is reportedly common.

Keywords: CDKN1A; Drug repositioning; MDM2; MDMX; P21WAF1/CIP1; repurposing.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / pharmacology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Repositioning
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Retinoblastoma / drug therapy*
  • Retinoblastoma / metabolism
  • Retinoblastoma / pathology
  • Signal Transduction / drug effects*
  • Tumor Suppressor Protein p53 / metabolism*


  • Antineoplastic Agents
  • Carbazoles
  • Cell Cycle Proteins
  • MDM4 protein, human
  • Proto-Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • 3,9-bis((ethylthio)methyl)-K-252a