PMID- 19662644
OWN - NLM
STAT- MEDLINE
DCOM- 20091113
LR  - 20220316
IS  - 1613-4133 (Electronic)
IS  - 1613-4125 (Linking)
VI  - 53
IP  - 9
DP  - 2009 Sep
TI  - EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through 
      activation of AMPK in p53 positive and negative human hepatoma cells.
PG  - 1156-65
LID - 10.1002/mnfr.200800592 [doi]
AB  - In the previous studies, (-)-epigallocatechin-3-gallate (EGCG) has been shown to 
      have anticarcinogenic effects via modulation in protein expression of p53. Using 
      p53 positive Hep G2 and p53 negative Hep 3B cells, we found that treatment of 
      EGCG resulted in dose-dependent inhibition of cellular proliferation, which 
      suggests that the interaction of EGCG with p53 may not fully explain its 
      inhibitory effect on proliferation. Caloric restriction (CR) reduces the 
      incidence and progression of spontaneous and induced tumors in laboratory 
      rodents. EGCG has multiple beneficial activities similar to those associated with 
      CR. One key enzyme thought to be activated during CR is AMP-activated kinase 
      (AMPK), a sensor of cellular energy levels. Here, we showed that EGCG activated 
      AMPK in both p53 positive and negative human hepatoma cells. The activation of 
      AMPK suppressed downstream substrates, such as mammalian target of rapamycin 
      (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and a 
      general decrease in mRNA translation. Moreover, EGCG activated AMPK decreases the 
      activity and/or expression of lipogenic enzymes, such as fatty acid synthase 
      (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the decision between 
      apoptosis and growth arrest following AMPK activation is greatly influenced by 
      p53 status. In p53 positive Hep G2 cells, EGCG blocked the progression of cell 
      cycle at G1 phase by inducing p53 expression and further up-regulating p21 
      expression. However, EGCG inducted apoptosis in p53 negative Hep 3B cells. Based 
      on these results, we have demonstrated that EGCG has a potential to be a 
      chemoprevention and anti-lipogenesis agent for human hepatoma cells.
FAU - Huang, Chi-Hung
AU  - Huang CH
AD  - Institute of Biochemistry, College of Life Science, National Chung Hsing 
      University, Taichung, Taiwan.
FAU - Tsai, Shang-Jie
AU  - Tsai SJ
FAU - Wang, Ying-Jan
AU  - Wang YJ
FAU - Pan, Min-Hsiung
AU  - Pan MH
FAU - Kao, Jung-Yie
AU  - Kao JY
FAU - Way, Tzong-Der
AU  - Way TD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Mol Nutr Food Res
JT  - Molecular nutrition & food research
JID - 101231818
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Acetyl-CoA Carboxylase/genetics
MH  - Anticarcinogenic Agents/*pharmacology
MH  - Carcinoma, Hepatocellular/*drug therapy/metabolism/pathology
MH  - Catechin/*analogs & derivatives/pharmacology
MH  - Cell Cycle/*drug effects
MH  - Cell Line, Tumor
MH  - Fatty Acid Synthases/genetics
MH  - Humans
MH  - Lipogenesis/*drug effects
MH  - Liver Neoplasms/*drug therapy/metabolism/pathology
MH  - Protein Biosynthesis/*drug effects
MH  - Protein Kinases/physiology
MH  - TOR Serine-Threonine Kinases
MH  - Tumor Suppressor Protein p53/*analysis/physiology
EDAT- 2009/08/08 09:00
MHDA- 2009/11/17 06:00
CRDT- 2009/08/08 09:00
PHST- 2009/08/08 09:00 [entrez]
PHST- 2009/08/08 09:00 [pubmed]
PHST- 2009/11/17 06:00 [medline]
AID - 10.1002/mnfr.200800592 [doi]
PST - ppublish
SO  - Mol Nutr Food Res. 2009 Sep;53(9):1156-65. doi: 10.1002/mnfr.200800592.