The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy

CBP-93872 suppresses maintenance of DNA double-stranded break-induced G2 checkpoint, by inhibiting the pathway between ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) activation. To examine the potential use of CBP-93872 for clinical applications, we analyzed the synergistic effe...

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Detalles Bibliográficos
Autores principales: Iwata, Tsutomu, Uchino, Tairin, Koyama, Ayako, Johmura, Yoshikazu, Koyama, Kenichi, Saito, Takuya, Ishiguro, Seiji, Arikawa, Takashi, Komatsu, Shunichiro, Miyachi, Masahiko, Sano, Tsuyoshi, Nakanishi, Makoto, Shimada, Midori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448762/
https://www.ncbi.nlm.nih.gov/pubmed/28558031
http://dx.doi.org/10.1371/journal.pone.0178221
Descripción
Sumario:CBP-93872 suppresses maintenance of DNA double-stranded break-induced G2 checkpoint, by inhibiting the pathway between ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) activation. To examine the potential use of CBP-93872 for clinical applications, we analyzed the synergistic effects of platinum-containing drugs, oxaliplatin and cisplatin, pyrimidine antimetabolites, gemcitabine and 5-fluorouracil (5-FU), in combination with CBP-93872, on cell lethality in colorectal and pancreatic cancer cell lines. Treatment with CBP-93872 significantly increased cancer cell sensitivities to various chemotherapeutic agents tested through suppression of checkpoint activation. Our results thus reveal that combination treatment of CBP-93872 with known chemotherapeutic agents inhibits phosphorylation of ATR and Chk1, and induces cell death.

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