Modulation of gene expression by (-)-epigallocatechin gallate in PC-9 cells using a cDNA expression array.
Green tea is the most effective cancer preventive beverage. In the light of this, the mechanisms of action of tea polyphenols were investigated on the molecular levels. We present here the effects of (-)-epigallocatechin gallate (EGCG) on expression of 588 genes in human lung cancer cell line PC-9 cells, using a human cancer cDNA expression array. The levels of gene expression in non-treated control cells, and cells treated with EGCG alone, with the tumor promoter okadaic acid alone, and with EGCG plus okadaic acid, were studied, and their expression levels were classified into down-regulation (under 0.5 fold) and up-regulation (over 2.0 fold) by comparing with the levels of control. Non-treated PC-9 cells expressed 163 genes out of 588, and EGCG-treated cells induced down-regulated expression of 12 genes and up-regulated expression of 4 other genes. From a comparison of gene expression in the cells treated with EGCG and in cells treated with EGCG plus okadaic acid, we found the following genes commonly affected by EGCG: down-regulation of four genes, NF-kappaB inducing kinase (NIK), death-associated protein kinase 1 (DAPK 1), rhoB and tyrosine-protein kinase (SKY); up-regulation of one gene, retinoic acid receptor alpha1. Among them, we think down-regulation of NIK gene expression is significant for cancer prevention, based on evidence that inhibition of NF-kappaB activation is a result of inhibition of NIK/IKK signalling complex.
Okabe
S
S
Saitama Cancer Center, Japan.
Fujimoto
N
N
Sueoka
N
N
Suganuma
M
M
Fujiki
H
H
D016587:Antimutagenic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015342:DNA Probes; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011061:Poly A / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D016587:Antimutagenic Agents; D015342:DNA Probes; D018076:DNA, Complementary; D016328:NF-kappa B; D011061:Poly A; D002392:Catechin; C045651:epigallocatechin gallate