title: Resveratrol enhances radiation sensitivity in prostate cancer by inhibiting cell proliferation and promoting cell senescence and apoptosis.
abstract: Radiation therapy (XRT) for treatment of localized prostate cancer (PCA) has outcomes similar to surgery and medical therapy. Toxicities of XRT and the relative radioresistance of PCA limit the effectiveness of this treatment method. Safe and effective radiosensitizing agents are lacking to enhance the effectiveness for XRT for PCA. In this study, the effect of XRT in combination with the radiosensitizing agent resveratrol (RSV) was investigated in a radioresistant PCA cell line, PC-3. Our results show the addition of RSV to XRT (XRT/RSV) synergistically enhanced XRT-induced apoptosis and inhibition of PC-3 proliferation. The antiproliferative effect of XRT/RSV treatment correlated with increased expression of p15, p21, and mutant p53 and decreased expression of cyclin B, cyclin D, and cdk2. Increased apoptosis correlated with increased expression of Fas and TRAILR1. Furthermore, XRT/RSV had little effect on the expression of p-AKT, whereas it increased the expression level of p-H2A.X, a marker for senescence. These data highlight the potential of RSV as a radiation sensitizer for PCA treatment and warrant further investigation.
authors.affiliation: Department of Surgery, University of Missouri School of Medicine, Columbia, Missouri, USA. fangy@health.missouri.edu
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Fang
authors.forename: Vincent G
authors.initials: VG
authors.lastname: DeMarco
authors.forename: Michael B
authors.initials: MB
authors.lastname: Nicholl
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D019926:Cyclin B / Q000378:metabolism; D056741:Cyclin D / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D019926:Cyclin B; D056741:Cyclin D; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053222:Fas Ligand Protein; C468783:H2AX protein, human; D006657:Histones; D011838:Radiation-Sensitizing Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D013267:Stilbenes; C105190:TNFRSF10A protein, human; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D053148:Caspase 3; D000077185:Resveratrol