Genome-scale analysis of resveratrol-induced gene expression profile in human ovarian cancer cells using a cDNA microarray.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural compound found in large quantities, most notably in grapes and red wine, which has been shown to have anti-inflammatory, chemopreventive and anti-angiogenic effects. We examined whether resveratrol has any effect on growth and gene expression in the human ovarian cancer PA-1 cells. We show that resveratrol inhibits cell growth and induces apoptosis in PA-1 human ovarian cancer cells. We also investigated the effect of resveratrol on changes of global gene expression during resveratrol-induced growth inhibition and apoptosis in PA-1 cells using a human cDNA microarray with 7,448 sequence-verified clones. Out of the 7,448 genes screened, 118 genes were founded to be affected in their expression levels by more than 2-fold after 24-h treatment with 50 micro M resveratrol. Resveratrol treatment of PA-1 cells at the final concentration of 50 micro M for 6, 12, 24 and 48 h and gene expression patterns were analyzed by microarray. Clustering of the genes modulated more than 2-fold at three of the above times points divided the genes into 2 groups. Within these groups, there were specific subgroups of genes whose expressions were substantially changed at the specified time points. One of the most highly up-regulated genes found in this study was NAD(P)H quinone oxidoreductase 1(NQO-1), which has recently been shown to be involved in p53 regulation. Although the precise roles of genes whose expression levels were found to fluctuate after resveratrol treatment remain to be elucidated, we hope that the new view of gene expression in human ovarian cancer cells following resveratrol exposure, as offered by this study, provides clues for the mechanism of resveratrol action.
Yang
Sang Hwa
SH
Microarray Division, GenomicTree, Inc., Daejon 305-390, Korea.
Kim
Jong Sik
JS
Oh
Tae Jeong
TJ
Kim
Myung Soon
MS
Lee
Sun Woo
SW
Woo
Suk Kyung
SK
Cho
Hyun Sill
HS
Choi
Yung Hyun
YH
Kim
Young Ho
YH
Rha
Sun Young
SY
Chung
Hyun Cheol
HC
An
Sung Whan
SW
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016678:Genome; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; D018076:DNA, Complementary; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D012313:RNA; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D000077185:Resveratrol