Celecoxib Toxicity Is Cell Cycle Phase Specific
作者： Jonathan M. Bock , Sarita G. Menon , Lori L. Sinclair , Nichole S. Bedford , Prabhat C. Goswami
DOI: 10.1158/0008-5472.CAN-06-3780
关键词:
摘要: Celecoxib inhibits proliferation and induces apoptosis in human tumors, but the molecular mechanisms for these processes are poorly understood. In this study, we evaluated ability of celecoxib to induce toxicity head neck squamous cell carcinomas (HNSCC) explored relationships between celecoxib-induced cycle inhibition HNSCC. inhibited UM-SCC-1 UM-SCC-17B cells both vitro vivo, accompanied by G1 phase arrest apoptosis. induced p21waf1/cip1 at transcriptional level independent wild-type p53 function, leading decreased expression cyclin D1 hypophosphorylation Rb, with subsequent marked downstream decreases nuclear E2F-1 protein E2F transactivating activity luciferase reporter assay. Cell phase–specific cytometric sorting showed that clonogenic preferentially within S greater than G2 phases. Levels were reduced compared phases, suggesting a possible protective role toxicity. conclusion, show has antiproliferative against cancer through induction accumulation We additionally profound function provides mechanism [Cancer Res 2007;67(8):3801–8]
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