Urolithin A causes p21 up-regulation in prostate cancer cells

作者：Sanchez Gonzalez Claudia; Ciudad Carlos J; Izquierdo Pulido Maria; Noe Veronique

来源：European Journal of Nutrition, 2016, 55(3): 1099-1112.

DOI：10.1007/s00394-015-0924-z

• Urolithin A
• Walnuts
• Ellagitannins cancer prevention

Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). The aim of this study was to determine gene expression changes in prostate cancer cells after incubation with UA.
We performed a genomic analysis to study the effect of UA on LNCaP prostate cells. Cells were incubated with 40 A mu M UA for 24 h, and RNA was extracted and hybridized to Affymetrix Human Genome U219 array. Microarray results were analyzed using GeneSpring v13 software. Differentially expressed genes (p < 0.05, fold change > 2) were used to perform biological association networks. Cell cycle was analyzed by flow cytometry and apoptosis measured by the rhodamine method and by caspases 3 and 7 activation. Cell viability was determined by MTT assay.
We identified two nodes, FN-1 and CDKN1A, among the differentially expressed genes upon UA treatment. CDKN1A was validated, its mRNA and protein levels were significantly up-regulated, and the promoter activation measured by luciferase. Cell cycle analysis showed an increase in G1-phase, and we also observed an induction of apoptosis and caspases 3 and 7 activation upon UA treatment.
Our results indicate a potential role of UA as a chemopreventive agent for prostate cancer.

• 出版日期2016-4