Gene expression profile in human prostate LNCaP cancer cells by (--) epigallocatechin-3-gallate.
Green tea is an effective chemopreventive agent in animal tumor bioassays and some human cancers. Much of its cancer preventive effects appear to be mediated by its major polyphenolic constituent (-) epigallocatechin-3-gallate (EGCG). In order to better understand the molecular regulation underlying the anti-proliferative activity of EGCG in prostate cancer, we have utilized cDNA microarray to elucidate how EGCG alters program of gene expression in prostate carcinoma LNCaP cells. Fluorophore-labeled cDNA probes synthesized from the untreated LNCaP cells or the cells treated for 12 h with EGCG (12 microM), a physiologically achievable dose, were competitively hybridized to the microarray that contained a total of 250 kinases and phosphatases genes. Such high-throughput screening has identified a number of EGCG-responsive gene candidates. Of these, we found that EGCG induced a subset of genes that functionally could exhibit inhibitory effects on cell growth. The genes repressed by EGCG mostly belonged to the G-protein signaling network. Interestingly, the protein kinase C-alpha (PKC-alpha) form, whose inhibition of expression has been shown to inhibit cell growth in some cancer cells, was selectively repressed by EGCG while the expression of six other PKC isoforms (beta, delta, epsilon, micro, eta and zeta) was unaffected. These EGCG-responsive genes may provide key insights from which to understand mechanisms of action of other polyphenolic compounds in prostate cancer chemoprevention.
Wang
Steven I
SI
Dermatology Department, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5028, USA.
Mukhtar
Hasan
H
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000517:prevention & control; D011493:Protein Kinase C / Q000235:genetics; D020917:Receptor, trkA / Q000235:genetics; D013662:Tea
D016588:Anticarcinogenic Agents; D007527:Isoenzymes; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D019869:Phosphatidylinositol 3-Kinases; D020917:Receptor, trkA; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases