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http://dx.doi.org/10.5483/BMBRep.2014.47.4.146

Nutlin-3 downregulates p53 phosphorylation on serine392 and induces apoptosis in hepatocellular carcinoma cells  

Shi, Xinli (Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University)
Liu, Jingli (Department of Repairing and Servicing Technology of Medical Equipment, Bethune Medical Non-commissioned Officer Academy of PLA)
Ren, Laifeng (Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University)
Mao, Nan (West China School of Medicine, Sichuan University)
Tan, Fang (West China School of Medicine, Sichuan University)
Ding, Nana (Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University)
Yang, Jing (Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University)
Li, Mingyuan (Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University)
Publication Information
BMB Reports / v.47, no.4, 2014 , pp. 221-226 More about this Journal
Abstract
Drug-resistance and imbalance of apoptotic regulation limit chemotherapy clinical application for the human hepatocellular carcinoma (HCC) treatment. The reactivation of p53 is an attractive therapeutic strategy in cancer with disrupted-p53 function. Nutlin-3, a MDM2 antagonist, has antitumor activity in various cancers. The post-translational modifications of p53 are a hot topic, but there are some controversy ideas about the function of phospho-$Ser^{392}$-p53 protein in cancer cell lines in response to Nutlin-3. Therefore, we investigated the relationship between Nutlin-3 and phospho-$Ser^{392}$-p53 protein expression levels in SMMC-7721 (wild-type TP53) and HuH-7 cells (mutant TP53). We demonstrated that Nutlin-3 induced apoptosis through down-regulation phospho-$Ser^{392}$-p53 in two HCC cells. The result suggests that inhibition of p53 phosphorylation on $Ser^{392}$ presents an alternative for HCC chemotherapy.
Keywords
Apoptosis; Human hepatocellular carcinoma; Nutlin-3; p53; Phospho-$Ser^{392}$-p53;
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