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

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 fibr...

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Published inAnticancer research Vol. 40; no. 9; pp. 4961 - 4968
Main Authors Togashi, Keita, Okada, Masashi, Suzuki, Shuhei, Sanomachi, Tomomi, Seino, Shizuka, Yamamoto, Masahiro, Yamashita, Hidetoshi, Kitanaka, Chifumi
Format Journal Article
LanguageEnglish
Published Athens International Institute of Anticancer Research 01.09.2020
Subjects
Activation
Biotechnology
Cancer
Cell lines
Deactivation
Enzyme inhibitors
Inactivation
Kinases
Medical treatment
Movement disorders
Neurodegenerative diseases
p53 Protein
Parkinson's disease
Retina
Retinoblastoma
Tumors
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Summary: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.
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ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.14499