Eugenia Yazlovitskaya
Faculty Member
Last active: 11/16/2017

Inhibition of cisplatin-induced ATR activity and enhanced sensitivity to cisplatin.

Yazlovitskaya EM, Persons DL
Anticancer Res. 2003 23 (3B): 2275-9

PMID: 12894503

Ataxia teleangiectasia mutated (ATM) kinase, ATM-Rad3-related (ATR) kinase and DNA-protein kinase (DNA-PK) belong to a subgroup of protein kinases which play a role in the DNA damage response. In this study, cisplatin was shown to increase ATR activity and decrease ATM and DNA-PK activity. Caffeine, a nonspecific inhibitor of ATR, enhanced the cytotoxic effect of cisplatin, modestly decreased the p53 and p21WAF-1 response to cisplatin, and affected the cdc2-p34/cyclin B1 complex by decreasing both cyclin B1 protein accumulation and cdc2-p34 tyrosine 15 phosphorylation. The observed alteration of several potential ATR downstream targets suggests that inhibition of ATR activity may be one of the mechanism by which caffeine regulates sensitivity to cisplatin.

MeSH Terms (22)

Adenocarcinoma Antineoplastic Agents Ataxia Telangiectasia Mutated Proteins Caffeine CDC2 Protein Kinase Cell Cycle Proteins Cisplatin Cyclin B Cyclin B1 DNA-Activated Protein Kinase DNA-Binding Proteins Drug Synergism Enzyme Induction Female Humans Nuclear Proteins Ovarian Neoplasms Phosphorylation Protein-Serine-Threonine Kinases Tumor Cells, Cultured Tumor Suppressor Protein p53 Tumor Suppressor Proteins

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