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Epigallocatechin-3-gallate regulates cell growth, cell cycle and phosphorylated nuclear factor-κB in human dermal fibroblasts

 Dong-Wook Han  ;  Mi Hee Lee  ;  Hak Hee Kim  ;  Suong-Hyu Hyon  ;  Jong-Chul Park 
 ACTA PHARMACOLOGICA SINICA, Vol.32(5) : 637-646, 2011 
Journal Title
Issue Date
Antioxidants/administration & dosage ; Antioxidants/pharmacology* ; Apoptosis/drug effects ; Camellia sinensis/chemistry ; Catechin/administration & dosage ; Catechin/analogs & derivatives* ; Catechin/pharmacology ; Cell Cycle/drug effects* ; Cell Proliferation/drug effects ; Cells, Cultured ; Cytoplasm/metabolism ; Dose-Response Relationship, Drug ; Fibroblasts/drug effects* ; Fibroblasts/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Infant, Newborn ; NF-kappa B/drug effects ; NF-kappa B/metabolism ; Oligonucleotide Array Sequence Analysis ; Phosphorylation/drug effects ; Skin/cytology ; Skin/drug effects
(−)epigallocatechin-3-gallate (EGCG) ; polyphenol ; green tea ; cell cycle ; fibroblasts ; nuclear factor-κB (NF-κB)
AIM: To investigate the effects of (-)epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, on cell growth, cell cycle and phosphorylated nuclear factor-κB (pNF-κB) expression in neonatal human dermal fibroblasts (nHDFs).

METHODS: The proliferation and cell-cycle of nHDFs were determined using WST-8 cell growth assay and flow cytometry, respectively. The apoptosis was examined using DNA ladder and Annexin V-FITC assays. The expression levels of pNF-κB and cell cycle-related genes and proteins in nHDFs were measured using cDNA microarray analyses and Western blot. The cellular uptake of EGCG was examined using fluorescence (FITC)-labeled EGCG (FITC-EGCG) in combination with confocal microscopy.

RESULTS: The effect of EGCG on the growth of nHDFs depended on the concentration tested. At a low concentration (200 μmol/L), EGCG resulted in a slight decrease in the proportion of cells in the S and G(2)/M phases of cell cycle with a concomitant increase in the proportion of cells in G(0)/G(1) phase. At the higher doses (400 and 800 μmol/L), apoptosis was induced. The regulation of EGCG on the expression of pNF-κB was also concentration-dependent, whereas it did not affect the unphosphorylated NF-κB expression. cDNA microarray analysis showed that cell cycle-related genes were down-regulated by EGCG (200 μmol/L). The expression of cyclins A/B and cyclin-dependent kinase 1 was reversibly regulated by EGCG (200 μmol/L). FITC-EGCG was found to be internalized into the cytoplasm and translocated into the nucleus of nHDFs.

CONCLUSION: EGCG, through uptake into cytoplasm, reversibly regulated the cell growth and expression of cell cycle-related proteins and genes in normal fibroblasts.
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1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Hak Hee(김학희)
Park, Jong Chul(박종철) ORCID logo https://orcid.org/0000-0003-0083-5991
Lee, Mi Hee(이미희) ORCID logo https://orcid.org/0000-0002-9630-7044
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