Literature DB >> 31519582

Ro 90-7501 Is a Novel Radiosensitizer for Cervical Cancer Cells that Inhibits ATM Phosphorylation.

Keisuke Tamari1, Keisuke Sano2,3, Zhihao Li2, Yuji Seo2, Keisuke Otani2, Shotaro Tatekawa2, Masayasu Toratani2, Yuji Takaoka2, Yutaka Takahashi2, Kazumasa Minami2, Fumiaki Isohashi2, Masahiko Koizumi3, Kazuhiko Ogawa2.   

Abstract

BACKGROUND/AIM: Ro 90-7501 has been reported as an inhibitor of the amyloid β42 fibril assembly that is associated with Alzheimer's disease. The present study aimed to elucidate the radiosensitizing effects of Ro 90-7501 and focused on ATM signaling after irradiation.
MATERIALS AND METHODS: Clonogenic survival, apoptosis, and cell-cycle assays as well as western blotting were performed in HeLa cells treated with irradiation and Ro 90-7501. Tumor growth delay assay was also performed using BALB/c-nu mice.
RESULTS: The combination of irradiation with Ro 90-7501 showed significant radiosensitizing effects in clonogenic survival and tumor growth delay assays. Ro 90-7501 significantly increased apoptosis and impaired cell cycle after irradiation. Western blotting showed that Ro 90-7501 suppressed the phosphorylation of ATM and its downstream proteins, such as H2AX, Chk1, and Chk2, after irradiation.
CONCLUSION: Ro 90-7501 inhibits DNA damage response by inhibiting ATM and has significant radiosensitizing effects on cervical cancer cells. Copyright
© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Entities:  

Keywords:  ATM; Ro 90-7501; cervical cancer; radiosensitizer

Mesh:

Substances:

Year:  2019        PMID: 31519582     DOI: 10.21873/anticanres.13665

Source DB:  PubMed          Journal:  Anticancer Res        ISSN: 0250-7005            Impact factor:   2.480


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