The identification of new agents that may modulate the progression of cancer cell growth is of great interest. In this regard, dietary agents can be utilized to identify molecular targets to be used as part of a chemo-preventive strategy. Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). We performed a genomic analysis to study the effect of UA on LNCaP prostate and MCF-7 breast adenocarcinoma cells. Cells were incubated with 40µM UA for 24 hours. Then, RNA was extracted, labeled and hybridized to Affymetrix Human Gene 2.1 ST Array, representing the whole human genome. Microarray results were analyzed using the GeneSpring 12.0 software. Differentially expressed genes (p < 0.05, FC >2) were selected. In both LNCaP and MCF-7 cells, among the differentially expressed genes, we identified a decreased expression of PDK1 and an up-regulation of CDKN1A, both of which have been linked to cancer progression. In MCF-7 cells we also observed an up-regulation of PTEN. The previously mentioned changes in gene expression were validated by RT-real time PCR. Cell cycle distribution and apoptosis were measured by flow cytometry after 24h incubation with UA. An increase in apoptotic cell population and cell cycle arrest were seen in both LNCaP and MCF-7 cells. Our results indicate a potential role of walnuts as a chemo-preventive agent for prostate and breast cancer. Study funded by a grant from the California Walnut Commission
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