title: Convergent Effects of Resveratrol and PYK2 on Prostate Cells.
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.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy. andrea.conte@unina.it.|Institute of Experimental Oncology and Endocrinology, National Research Council of Italy, 80131 Naples, Italy. andrea.conte@unina.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Conte
authors.affiliation: Institute of Experimental Oncology and Endocrinology, National Research Council of Italy, 80131 Naples, Italy. a.kisslinger@ieos.cnr.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Kisslinger
authors.affiliation: Institute of Experimental Oncology and Endocrinology, National Research Council of Italy, 80131 Naples, Italy. claudio.procaccini@cnr.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Procaccini
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy. spaladin@unina.it.|Centro di Ingegneria Genetica (CEINGE)-Biotecnologie Avanzate, 80131 Naples, Italy. spaladin@unina.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Paladino
authors.affiliation: Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, 80131 Naples, Italy. olivier@unina.it.
authors.forename: Olimpia
authors.initials: O
authors.lastname: Oliviero
authors.affiliation: Centro Sanitario, University of Calabria, 87036 Rende (CS), Italy. francesca.deamicis@unical.it.|Department of Pharmacy, Health Science and Nutrition, University of Calabria, 87036 Rende (CS), Italy. francesca.deamicis@unical.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: de Amicis
authors.affiliation: Department of Medical and Translational Science, University Federico II of Naples, 80131 Naples, Italy. d.faicchia@libero.it.
authors.forename: Deriggio
authors.initials: D
authors.lastname: Faicchia
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy. dominga.fasano@gmail.com.
authors.forename: Dominga
authors.initials: D
authors.lastname: Fasano
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy. marilenacaputo86@gmail.com.
authors.forename: Marilena
authors.initials: M
authors.lastname: Caputo
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy. giuseppe.matarese@unina.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy. gmpieran@unina.it.
authors.forename: Giovanna Maria
authors.initials: GM
authors.lastname: Pierantoni
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy. dtramont@unina.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Tramontano
mesh_terms: D000975:Antioxidants / Q000493:pharmacokinetics*; D001343:Autophagy; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D051418:Focal Adhesion Kinase 2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D051418:Focal Adhesion Kinase 2; D000077185:Resveratrol
keywords: autophagy; cell morphology; cell size; proline-rich tyrosine kinase 2 (PYK2); prostate cells; reactive oxygen species (ROS); resveratrol