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Resveratrol-Induced Gene Expression Profiles in Human Prostate Cancer Cells

Departments of ¹ Urology and ² Genetics, Stanford University School of Medicine, Stanford, California

Requests for reprints: James D. Brooks, Department of Urology, Stanford University School of Medicine, MC 5118, Stanford, CA 94305. Phone: 650-498-4464; Fax: 650-723-0765. E-mail: jdbrooks{at}stanford.edu

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: Resveratrol produces gene expression changes in the androgen axis and cell cycle regulators that may underlie its putative anticancer activities in prostate cancer.

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