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Life Sci 2002
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Mar 1;70(15):1821-39 Related Articles, Books, LinkOut
- Interactive gene expression pattern in prostate cancer cells exposed to
phenolic antioxidants.
Narayanan BA, Narayanan NK, Stoner GD, Bullock BP.
Microarray Systems Laboratory, American Health Foundation, Valhalla, NY 10595,
USA. bhagavat@mindspring.com
Dietary phenolic compounds are known to elicite vital cellular responses such
as cell cycle arrest, apoptosis and differentiation by activating a cascade of
molecular events. As there is an increasing interest to improve the efficacy
of these compounds for use as potential chemopreventive agents, we wanted to
understand the impact of phenolic compounds on target genes in prostate
cancer. In this study we used human cDNA microarrays with 2400 clones
consisting of 17 prosite motifs to characterize alterations in gene expression
pattern in response to the phenolic antioxidants ellagic acid (EA) and
resveratrol (RE). Over a 48-hr exposure of androgen - sensitive LNCaP cells to
EA and RE, a total of 593 and 555 genes respectively, showed more than a two
fold difference in expression. A distinct set of genes in both EA-and
RE-treated cells may represent the signature profile of phenolic
antioxidant-induced gene expression in LNCaP cells. Although extensive
similarity was found between effects of EA - and RE - responsive genes in
prostate cancer cells, out of 246 genes with overlapping responses, 25 genes
showed an opposite effect. Quantitative RT-PCR was used to verify and validate
the differential expression of selected genes identified from cDNA microarrays.
In-depth analysis of the data from this study provided insight into the
alterations in the p53 - responsive genes, p300, Apaf-1, NF-kBp50 and p65 and
PPAR families of genes, suggesting the activation of multiple signaling
pathways that leads to growth inhibition of LNCaP cells. This is a first study
to look for changes in a large number of human genes in response to dietary
compounds.
