title: Epigallocatechin-3-gallate regulates the expression of Kruppel-like factor 4 through myocyte enhancer factor 2A.
abstract: Epigallocatechin-3-gallate (EGCG), a powerful antioxidant and free ion scavenger found in green tea, exhibits inhibitory effects on different stages of tumorigenesis. Within gastric cancer cells, the transcription factor Kruppel-like factor 4 (KLF4) is downregulated, and it is possible that EGCG exerts its anti-tumorigenic function through modulation of KLF4 expression. In order to examine the effects of EGCG on KLF4 in a gastric tumor model, we treated the gastric cancer cell line NCI-N87 with EGCG. We found that EGCG treatment results in increased expression of KLF4 and alters expression of the KLF4 target genes p21, CDK4, and cyclin D1. EGCG inhibits the growth of NCI-N87 cells in a time- and dose-dependent manner through arresting the cell cycle in the G0/G1 phase. Furthermore, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and 4',6-diamidino-2-phenylindole staining revealed that EGCG is able to promote apoptosis of NCI-N87 cells. The suppressive effects of EGCG on cell growth and cell cycle protein expression are eliminated by decreasing KLF4 mRNA using siRNA and are magnified by overexpressing KLF4. Using KLF4 reporter constructs, we verified that the elevated expression induced by EGCG was mediated by increasing levels of activated MEF2A, which bound to the promoter region of KLF4. Taken together, this is the first time that EGCG is reported to increase the expression of KLF4, suggesting a novel mechanisms in gastric cancer treatment.
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Hospital of WeiFang Medical University, No. 465 Yuhe Road, Kuiwen District, Weifang City, Shandong, 261031, People's Republic of China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Ma
authors.forename: Youkui
authors.initials: Y
authors.lastname: Shi
authors.forename: Wenmei
authors.initials: W
authors.lastname: Li
authors.forename: Aijuan
authors.initials: A
authors.lastname: Sun
authors.forename: Ping
authors.initials: P
authors.lastname: Zang
authors.forename: Peirong
authors.initials: P
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D064326:MEF2 Transcription Factors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D012333:RNA, Messenger; D002392:Catechin; C045651:epigallocatechin gallate