Gene expression changes induced by green tea polyphenol (-)-epigallocatechin-3-gallate in human bronchial epithelial 21BES cells analyzed by DNA microarray.
Many studies suggest green tea is a cancer chemopreventive agent. This effect has been attributed to its major constituent (-)-epigallocatechin-3-gallate (EGCG). EGCG is also observed to have cytotoxic anticancer effects, especially when used in combination with certain chemotherapeutic agents. The biochemical actions of EGCG in chemoprevention and anticancer effects have been studied; however, the mechanisms of action are not clearly understood. We show here by expression genomics the effects of EGCG (25 micromol/L) in the Ha-ras gene transformed human bronchial epithelial 21BES cells. We found induction of temporal changes in gene expression and the coalescence of specific genetic pathways by EGCG. In this experimental system, hydrogen peroxide (H2O2) was produced. By treating cells with EGCG in the presence or absence of catalase, we further distinguished gene expression changes that are mediated by H2O2 from those that are H2O2 independent. Many genes and cellular pathways, including genes of the transforming growth factor-beta signaling pathway, were H2O2 dependent because the effects were abolished by catalase. Gene expression changes that were not affected by catalase included those of the bone morphogenetic protein signaling pathway, peptidylprolyl isomerase (cyclophilin)-like 2, alkylated DNA repair enzyme alkB, polyhomeotic-like 2, and homeobox D1. We show further that EGCG and H2O2 differentially transactivated the bone morphogenetic protein and the transforming growth factor-beta response element promoter reporters, respectively, thus confirming results from DNA microarray analysis. The elucidation of gene expression changes between H2O2-dependent and H2O2-independent responses helps us better understand the cancer chemopreventive and anticancer actions of EGCG.
Vittal
Ragini
R
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Selvanayagam
Zachariah E
ZE
Sun
Yi
Y
Hong
Jungil
J
Liu
Fang
F
Chin
Khew-Voon
KV
Yang
Chung S
CS
D000071498:AlkB Homolog 1, Histone H2a Dioxygenase; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001980:Bronchi / Q000166:cytology; D002374:Catalase / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002461:Cell Line, Transformed; D045643:DNA Repair Enzymes; D004847:Epithelial Cells / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D011905:Genes, ras / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D019696:Peptidylprolyl Isomerase / Q000235:genetics; D010636:Phenols / Q000494:pharmacology; D063151:Polycomb Repressive Complex 2; D059808:Polyphenols; D013662:Tea / Q000737:chemistry; D014157:Transcription Factors
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D029968:Escherichia coli Proteins; D005419:Flavonoids; C442019:HOXD1 protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C485977:PHC2 protein, human; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D014157:Transcription Factors; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D006899:Mixed Function Oxygenases; D002374:Catalase; C499236:ALKBH1 protein, human; D000071498:AlkB Homolog 1, Histone H2a Dioxygenase; D063151:Polycomb Repressive Complex 2; D019696:Peptidylprolyl Isomerase; D045643:DNA Repair Enzymes