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Urolithin A causes p21 up-regulation in prostate cancer cells

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Abstract

Purpose

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.

Methods

We performed a genomic analysis to study the effect of UA on LNCaP prostate cells. Cells were incubated with 40 µM 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.

Results

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.

Conclusion

Our results indicate a potential role of UA as a chemopreventive agent for prostate cancer.

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Acknowledgments

This work was supported by grants from the California Walnut Commission (FBG-306913) and Spanish Government of Science and Innovation (SAF2011-23582 and SAF2014-51825-R). C.S.G. was supported by a scholarship from the “Consejo Nacional de Ciencia y Tecnología, CONACYT” from Mexico. Our group holds the Quality Mention from the Government of Catalonia, Spain (2014SGR96).

Conflict of interest

Authors have no potential conflict of interest.

Author information

Authors and Affiliations

  1. Nutrition and Food Science Department, University of Barcelona, 08028, Barcelona, Spain

    Claudia Sánchez-González & Maria Izquierdo-Pulido

  2. Biochemistry and Molecular Biology Department, School of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain

    Carlos J. Ciudad & Véronique Noé

  3. CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Barcelona, Spain

    Maria Izquierdo-Pulido

Authors
  1. Claudia Sánchez-González
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  2. Carlos J. Ciudad
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  3. Maria Izquierdo-Pulido
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  4. Véronique Noé
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Corresponding author

Correspondence to Carlos J. Ciudad.

Additional information

Véronique Noé and Maria Izquierdo-Pulido share senior authorship.

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Sánchez-González, C., Ciudad, C.J., Izquierdo-Pulido, M. et al. Urolithin A causes p21 up-regulation in prostate cancer cells. Eur J Nutr 55, 1099–1112 (2016). https://doi.org/10.1007/s00394-015-0924-z

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  • DOI: https://doi.org/10.1007/s00394-015-0924-z

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