Reference - Detail
| RRC ID | 63038 |
|---|---|
| Author | Togashi K, Okada M, Suzuki S, Sanomachi T, Seino S, Yamamoto M, Yamashita H, Kitanaka C. |
| Title | Inhibition of Retinoblastoma Cell Growth by CEP1347 Through Activation of the P53 Pathway. |
| Journal | Anticancer Res |
| Abstract |
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. |
| Volume | 40(9) |
| Pages | 4961-4968 |
| Published | 2020-9-1 |
| DOI | 10.21873/anticanres.14499 |
| PII | 40/9/4961 |
| PMID | 32878784 |
| MeSH | 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* |
| IF | 1.994 |
| Resource | |
| Human and Animal Cells | NCC-RbC-60(RCB2213) NCC-RbC-83(RCB2217) NCC-RbC-54(RCB2208) |