Reference - Detail
RRC ID | 52247 |
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Author | Iwata T, Uchino T, Koyama A, Johmura Y, Koyama K, Saito T, Ishiguro S, Arikawa T, Komatsu S, Miyachi M, Sano T, Nakanishi M, Shimada M. |
Title | The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy. |
Journal | PLoS One |
Abstract |
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. |
Volume | 12(5) |
Pages | e0178221 |
Published | 2017-5-30 |
DOI | 10.1371/journal.pone.0178221 |
PII | PONE-D-17-08156 |
PMID | 28558031 |
PMC | PMC5448762 |
MeSH | Aniline Compounds / pharmacology* Antineoplastic Agents / administration & dosage Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use* Antineoplastic Combined Chemotherapy Protocols Apoptosis / drug effects Ataxia Telangiectasia Mutated Proteins / metabolism Cell Line, Tumor Checkpoint Kinase 1 / metabolism Colorectal Neoplasms / drug therapy* Colorectal Neoplasms / pathology Drug Synergism G2 Phase / drug effects* Humans Pancreatic Neoplasms / drug therapy* Pancreatic Neoplasms / pathology Phosphorylation Propanolamines / pharmacology* |
IF | 2.74 |
Times Cited | 3 |
Resource | |
Human and Animal Cells | PANC-1(RCB2095) |