Article

Resveratrol-induced gene expression profiles in human prostate cancer cells

Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.32). 03/2005; 14(3):596-604. DOI: 10.1158/1055-9965.EPI-04-0398
Source: PubMed

ABSTRACT The transhydroxystilbene resveratrol is found at high levels in red wine and grapes, and red wine consumption may be inversely associated with prostate cancer risk. To gain insights into the possible mechanisms of action of resveratrol in human prostate cancer, we did DNA microarray analysis of the temporal transcriptional program induced by treatment of the human prostate cancer cell line LNCaP with resveratrol.
Spotted DNA microarrays containing over 42,000 elements were used to obtain a global view of the effects of resveratrol on gene expression. Prostate-specific antigen (PSA) and androgen receptor (AR) expression were determined by Northern blot and immunoblot analyses. Cell proliferation was determined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay and cell cycle analysis by flow cytometry.
We observed time-dependent expression changes in >1,600 transcripts as early as 6 hours after treatment with resveratrol. Most striking was the modulation of a number of important genes in the androgen pathway including PSA and AR. Resveratrol also down-regulated expression of cell cycle and proliferation-specific genes involved in all phases of the cell cycle, induced negative regulators of proliferation, caused accumulation of cells at the sub-G1 and S phases of the cell cycle, and inhibited cell proliferation in a time- and dose-dependent manner.
Resveratrol produces gene expression changes in the androgen axis and cell cycle regulators that may underlie its putative anticancer activities in prostate cancer.

Download full-text

Full-text

Available from: James D Brooks, Aug 25, 2015
0 Followers
 · 
79 Views
  • Source
    • "Resveratrol , downregulating the expression of both genes , is known to cause an accumulation of cells at the sub - G1 and S phases of the cell cycle , and inhibits cell proliferation depending on time and dose in LNCaP prostate cancer cell lines ( Jones et al . 2005 ) . Moreover , the downregulation of CDK2 after resveratrol treatment in incubated embryonic cardiomyoblasts may explain the accumulation of cell populations in the G1 phase ( Leong et al . 2007 ) . Dexamethasone , on the other hand , increased the expres - sion of CDK1 and CDK2 in our qRT - PCR assay . These data do not support the red"
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily attacks joints and is therefore a common cause of chronic disability and articular destruction. The hyperplastic growth of RA-fibroblast-like synoviocytes (FLSs) and their resistance against apoptosis are considered pathological hallmarks of RA. The natural antioxidant resveratrol is known for its antiproliferative and pro-apoptotic properties. This study investigated the effect of resveratrol on RA-FLS. RA-FLS were isolated from the synovium of 10 RA patients undergoing synovectomy or joint replacement surgery. RA-FLS were first stressed by pre-incubation with interleukin 1beta (IL-1β) and then treated with 100μM resveratrol for 24h. In order to evaluate the influence of resveratrol on the transcription of genes, a Gene Chip Human Gene 1.0 ST Array was applied. In addition, the effect of dexamethasone on proliferation and apoptosis of RA-FLS was compared with that of resveratrol. Gene array analysis showed highly significant effects of resveratrol on the expression of genes involved in mitosis, cell cycle, chromosome segregation and apoptosis. qRT-PCR, caspase-3/7 and proliferation assays confirmed the results of gene array analysis. In comparison, dexamethasone showed little to no effect on reducing cell proliferation and apoptosis. Our in vitro findings point towards resveratrol as a promising new therapeutic approach for local intra-articular application against RA, and further clinical studies will be necessary.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 11/2012; 20(3-4). DOI:10.1016/j.phymed.2012.09.020 · 2.88 Impact Factor
  • Source
    • "RES has also been found to decrease expression of prostate-specific antigen (PSA), an androgenresponsive gene (ARG) often used as a marker for prostate cancer cell growth [17]. Moreover, a recent microarray study revealed that RES exerted global effects on ARG expression in LNCaP cells [22]. ARGs such as PSA play important roles in cellular functions, including cell cycle regulation, transcription , cell proliferation, differentiation as well as metabolism [23] [24]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Stilbenes are phytoalexins that become activated when plants are stressed. These compounds exist in foods and are widely consumed. Resveratrol is a grape-derived stilbene, which possesses a wide range of health-promoting activities, including anticancer properties. Several other stilbenes structurally similar to resveratrol are also available in food, but their biological activities remain largely unknown. In this study, we compared the effects of resveratrol and its natural derivatives pterostilbene, trans-resveratrol trimethylether, trans-pinostilbene and trans-desoxyrhapontigenin on androgen-responsive human prostate cancer LNCaP cells. We found that these compounds exert differential effects on LNCaP cell growth, cell cycle and apoptosis. Trans-resveratrol trimethylether appeared to be the most potent compound among the stilbenes tested. Treatment of LNCaP cells with trans-resveratrol trimethylether resulted in G2/M blockage while other compounds, including resveratrol, induced G1/S arrest. Moreover, different from other compounds, trans-resveratrol trimethylether induced apoptosis. At the molecular level, the effects of these compounds on cell cycle correlated with induction of the cyclin-dependent kinase inhibitor 1A and B mRNA levels. Additionally, these compounds also inhibited both androgen- as well as estrogen-mediated pathways. These results provide mechanistic information on how resveratrol and its methylether analogs may act to contribute to potential antiprostate cancer activity.
    Molecular Nutrition & Food Research 03/2010; 54(3):335-44. DOI:10.1002/mnfr.200900143 · 4.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Resveratrol shows chemopreventive and other biological affects in in vitro and some animal studies. The bioactivities of resveratrol may be attributed to qualitative and quantitative differences in its cell-type-specific interaction and binding with its cellular targets, denoted as resveratrol targeting proteins (RTPs). To isolate RTPs, resveratrol was linked to epoxy-activated agarose generating an affinity platform to allow the isolation, purification, and characterization of distinct RTPs from cultured prostate cancer cell extracts. Glutathione sulfotransferase-pi (GSTP1) and estrogen receptor-beta (ER-beta) were found to be new RTPs. Resveratrol affinity chromatography was shown to be an easy method for analyzing resveratrol-responsive protein changes in the androgen-dependent LNCaP cells. Resveratrol affects cellular functions at multiple levels, ranging from interaction with detoxification enzymes, such as GSTP1 and transcription by targeting factors such as ER-beta.
    Anticancer research 01/2008; 28(1A):29-36. · 1.87 Impact Factor
Show more