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http://purl.uniprot.org/citations/22029423http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Prostate cancer (PrCa) displays resistance to radiotherapy (RT) and requires radiotherapy dose escalation which is associated with greater toxicity. This highlights a need to develop radiation sensitizers to improve the efficacy of RT in PrCa. Ionizing radiation (IR) stimulates pathways of IR-resistance and survival mediated by the protein kinase Akt but it also activates the metabolic energy sensor and tumor suppressor AMP-Activated Protein Kinase (AMPK). Here, we examined the effects of the polyphenol resveratrol (RSV) on the IR-induced inhibition of cell survival, modulation of cell cycle and molecular responses in PrCa cells.

Methods

Androgen-insensitive (PC3), sensitive (22RV1) PrCa and PNT1A normal prostate epithelial cells were treated with RSV alone (2.5-10 μM) or in combination with IR (2-8 Gy). Clonogenic assays, cell cycle analysis, microscopy and immunoblotting were performed to assess survival, cell cycle progression and molecular responses.

Results

RSV (2.5-5 μM) inhibited clonogenic survival of PC3 and 22RV1 cells but not of normal prostate PNT1A cells. RSV specifically sensitized PrCa cells to IR, induced cell cycle arrest at G1-S phase and enhanced IR-induced nuclear aberrations and apoptosis. RSV enhanced IR-induced expression of DNA damage (γH2Ax) and apoptosis (cleaved-caspase 3) markers as well as of the cell cycle regulators p53, p21(cip1) and p27(kip1). RSV enhanced IR-activation of ATM and AMPK but inhibited basal and IR-induced phosphorylation of Akt.

Conclusions

Our results suggest that RSV arrests cell cycle, promotes apoptosis and sensitizes PrCa cells to IR likely through a desirable dual action to activate the ATM-AMPK-p53-p21(cip1)/p27(kip1) and inhibit the Akt signalling pathways."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.org/dc/terms/identifier"doi:10.1186/1748-717x-6-144"xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Liu C."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Singh G."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Wright J."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Bristow R.G."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Rashid A."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Tsakiridis T."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Dayes I."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Lukka H."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Sanli T."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/author"Tsiani E."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/name"Radiat Oncol"xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/pages"144"xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/title"Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways."xsd:string
http://purl.uniprot.org/citations/22029423http://purl.uniprot.org/core/volume"6"xsd:string
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