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Convergent Effects of Resveratrol and PYK2 on Prostate Cells
- 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.
- Subjects :
- Male
0301 basic medicine
Resveratrol
resveratrol
Cell morphology
Antioxidants
Prostate cell
lcsh:Chemistry
chemistry.chemical_compound
RNA interference
Stilbenes
proline-rich tyrosine kinase 2 (PYK2)
lcsh:QH301-705.5
Spectroscopy
cell morphology
Prostate
General Medicine
Computer Science Applications
Cell biology
cell size
Biochemistry
Tyrosine kinase 2
prostate cells
Tyrosine kinase
autophagy
Biology
reactive oxygen species (ROS)
Cell size
Article
Catalysis
Cell Line
Inorganic Chemistry
03 medical and health sciences
Humans
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Organic Chemistry
Autophagy
Oxidative Stress
Focal Adhesion Kinase 2
030104 developmental biology
Gene Expression Regulation
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Apoptosis
Cell culture
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 17
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....4ccf1fee88f5f19c8356e0a4b1697412
- Full Text :
- https://doi.org/10.3390/ijms17091542