Mdm2 inhibition induces apoptosis in p53 deficient human colon cancer cells by activating p73- and E2F1-mediated expression of PUMA and Siva-1
作者： Ramesh M. Ray , Sujoy Bhattacharya , Leonard R. Johnson
DOI: 10.1007/S10495-010-0538-0
关键词:
摘要: Camptothecin (CPT) and Nutlin-3 caused apoptosis by increasing p53 protein its activation in intestinal epithelial cells (IEC-6). We studied the effectiveness of these inducers on human colon cancer (Caco2) lacking expression. CPT failed to activate caspase-3 cause cells. The absence expression, higher basal Bcl-xL lower Bax proteins prevented CPT-induced apoptosis. However, Mdm2 antagonist induced a dose dependent manner activating caspases-9 -3. AKT via PTEN-mediated inhibition PI3K pathway. increased phosphorylation retinoblastoma causing E2F1 release leading induction Siva-1. Nutlin-3-mediated degradation accumulation p73, which expression up-regulated modulator (PUMA). p73 knockdown decreased Siva PUMA, respectively abolished Nutlin-3-induced activation. Cycloheximide (CHX) inhibited Siva, Noxa, PUMA IEC-6 Caco2 These results indicate that translation mRNAs is critical for In summary, functional occurred following disruption binding with Rb pro-apoptotic proteins,
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