Open Access Highly Accessed Research

Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways

Ayesha Rashid12, Caiqiong Liu1, Toran Sanli13, Evangelia Tsiani4, Gurmit Singh3, Robert G Bristow5, Ian Dayes2, Himu Lukka2, James Wright2 and Theodoros Tsakiridis12*

Author Affiliations

1 Translational Radiation Biology Laboratory, Juravinski Cancer Centre, 699 Concession Street, Hamilton, Ontario, L84 5C2, Canada

2 Department of Oncology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4L8, Canada

3 Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4L8, Canada

4 Department of Community Health Science, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario, L2S 3A1, Canada

5 Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada

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Radiation Oncology 2011, 6:144  doi:10.1186/1748-717X-6-144

Published: 26 October 2011



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.


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.


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, p21cip1 and p27kip1. RSV enhanced IR-activation of ATM and AMPK but inhibited basal and IR-induced phosphorylation of Akt.


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-p21cip1/p27kip1 and inhibit the Akt signalling pathways.

radio-sensitizers; clonogenic survival; cell cycle; ATM; p53; p21cip1