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Convergent Effects of Resveratrol and PYK2 on Prostate Cells

Authors :
Marilena Caputo
Giuseppe Matarese
Claudio Procaccini
Andrea Conte
Annamaria Kisslinger
Donatella Tramontano
Deriggio Faicchia
Francesca De Amicis
Olimpia Oliviero
Simona Paladino
Dominga Fasano
Giovanna Maria Pierantoni
Conte, Andrea
Kisslinger, Annamaria
Procaccini, Claudio
Paladino, Simona
Oliviero, Olimpia
De Amicis, Francesca
Faicchia, Deriggio
Fasano, Dominga
Caputo, Marilena
Matarese, Giuseppe
Pierantoni, GIOVANNA MARIA
Tramontano, Donatella
Source :
International Journal of Molecular Sciences, Vol 17, Iss 9, p 1542 (2016), International Journal of Molecular Sciences, International Journal of Molecular Sciences; Volume 17; Issue 9; Pages: 1542, International journal of molecular sciences (Online) 17 (2016). doi:10.3390/ijms17091542, info:cnr-pdr/source/autori:Conte A.; Kisslinger A.; Procaccini C.; Paladino S.; Oliviero O.; De Amicis F.; Faicchia D.; Fasano D.; Caputo M.; Matarese G.; Pierantoni G.M.; Tramontano D./titolo:Convergent effects of resveratrol and PYK2 on prostate cells/doi:10.3390%2Fijms17091542/rivista:International journal of molecular sciences (Online)/anno:2016/pagina_da:/pagina_a:/intervallo_pagine:/volume:17
Publication Year :
2016
Publisher :
MDPI AG, 2016.

Abstract

Resveratrol, a dietary polyphenol, is under consideration as chemopreventive and chemotherapeutic agent for several diseases, including cancer. However, its mechanisms of action and its effects on non-tumor cells, fundamental to understand its real efficacy as chemopreventive agent, remain largely unknown. Proline-rich tyrosine kinase 2 (PYK2), a non-receptor tyrosine kinase acting as signaling mediator of different stimuli, behaves as tumor-suppressor in prostate. Since, PYK2 and RSV share several fields of interaction, including oxidative stress, we have investigated their functional relationship in human non-transformed prostate EPN cells and in their tumor-prone counterpart EPN-PKM, expressing a PYK2 dead-kinase mutant. We show that RSV has a strong biological activity in both cell lines, decreasing ROS production, inducing morphological changes and reversible growth arrest, and activating autophagy but not apoptosis. Interestingly, the PYK2 mutant increases basal ROS and autophagy levels, and modulates the intensity of RSV effects. In particular, the anti-oxidant effect of RSV is more potent in EPN than in EPN-PKM, whereas its anti-proliferative and pro-autophagic effects are more significant in EPN-PKM. Consistently, PYK2 depletion by RNAi replicates the effects of the PKM mutant. Taken together, our results reveal that PYK2 and RSV act on common cellular pathways and suggest that RSV effects on prostate cells may depend on mutational-state or expression levels of PYK2 that emerges as a possible mediator of RSV mechanisms of action. Moreover, the observation that resveratrol effects are reversible and not associated to apoptosis in tumor-prone EPN-PKM cells suggests caution for its use in humans.

Details

Language :
English
ISSN :
14220067
Volume :
17
Issue :
9
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....4ccf1fee88f5f19c8356e0a4b1697412