title: Epigallocatechin gallate promotes p53 accumulation and activity via the inhibition of MDM2-mediated p53 ubiquitination in human lung cancer cells.
abstract: Epigallocatechin gallate (EGCG), which is derived from green tea, is well known for its chemopreventive activity. Several studies have shown that p53 plays an important role in the activity of EGCG; however, the mechanism by which EGCG regulates p53 requires further investigation. In the present study, we showed that EGCG inhibits anchorage-independent growth of human lung cancer cells by upregulating p53 expression. EGCG treatment can substantially increase p53 stability, promote nuclear localization of p53 and decrease nuclear accumulation of MDM2. We also found that EGCG increases the phosphorylation of p53 at Ser15 and Ser20 and enhances its transcriptional activity. Although EGCG promotes MDM2 expression in a p53-dependent manner, the interaction between MDM2 and p53 was significantly inhibited following EGCG treatment, which resulted in the inhibition of MDM2-mediated p53 ubiquitination. Thus, our results suggest that the stabilization and activation of p53 may partly contribute to the anticancer activity of EGCG.
authors.affiliation: Cardiothoracic Surgery, The Third XiangYa Hospital, Central South University, Changsha, Hunan 410013, PR China.
authors.forename: Longyu
authors.initials: L
authors.lastname: Jin
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Liu
authors.forename: Dianjun
authors.initials: D
authors.lastname: Wang
authors.forename: Cao
authors.initials: C
authors.lastname: Hong
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Jiang
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Ma
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Fenglei
authors.initials: F
authors.lastname: Yu
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013662:Tea / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C495901:TP53 protein, human; D013662:Tea; D016159:Tumor Suppressor Protein p53; D002392:Catechin; C045651:epigallocatechin gallate; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D046988:Proteasome Endopeptidase Complex