title: Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy include senescence, necrosis, and autophagy, but not apoptosis.
abstract: In comparison to more differentiated cells, prostate cancer stem-like cells are radioresistant, which could explain radio-recurrent prostate cancer. Improvement of radiotherapeutic efficacy may therefore require combination therapy. We have investigated the consequences of treating primary prostate epithelial cells with gamma irradiation and photodynamic therapy (PDT), both of which act through production of reactive oxygen species (ROS). Primary prostate epithelial cells were cultured from patient samples of benign prostatic hyperplasia and prostate cancer prior to treatment with PDT or gamma irradiation. Cell viability was measured using MTT and alamar blue assay, and cell recovery by colony-forming assays. Immunofluorescence of gamma-H2AX foci was used to quantify DNA damage, and autophagy and apoptosis were assessed using Western blots. Necrosis and senescence were measured by propidium iodide staining and beta-galactosidase staining, respectively. Both PDT and gamma irradiation reduced the colony-forming ability of primary prostate epithelial cells. PDT reduced the viability of all types of cells in the cultures, including stem-like cells and more differentiated cells. PDT induced necrosis and autophagy, whereas gamma irradiation induced senescence, but neither treatment induced apoptosis. PDT and gamma irradiation therefore inhibit cell growth by different mechanisms. We suggest these treatments would be suitable for use in combination as sequential treatments against prostate cancer.
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, Heslington, North Yorkshire, YO10 5DD, United Kingdom.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Frame
authors.affiliation: Department of Chemistry, University of Hull, Kingston Upon Hull, HU6 7RX, United Kingdom.
authors.forename: Huguette
authors.initials: H
authors.lastname: Savoie
authors.affiliation: Department of Chemistry, University of Hull, Kingston Upon Hull, HU6 7RX, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bryden
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 2AJ, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Giuntini
authors.affiliation: Department of Urology, Castle Hill Hospital (Hull and East Yorkshire Hospitals NHS Trust), Cottingham, HU16 5JQ, United Kingdom.|Hull York Medical School, University of Hull, Hull, HU6 7RX, United Kingdom.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Mann
authors.affiliation: Department of Urology, Castle Hill Hospital (Hull and East Yorkshire Hospitals NHS Trust), Cottingham, HU16 5JQ, United Kingdom.|Hull York Medical School, University of Hull, Hull, HU6 7RX, United Kingdom.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Simms
authors.affiliation: Department of Chemistry, University of Hull, Kingston Upon Hull, HU6 7RX, United Kingdom.
authors.forename: Ross W
authors.initials: RW
authors.lastname: Boyle
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, Heslington, North Yorkshire, YO10 5DD, United Kingdom.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Maitland
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D001343:Autophagy / Q000187:drug effects / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004847:Epithelial Cells / Q000378:metabolism* / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000235:genetics; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011467:Prostate / Q000166:cytology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species
keywords: Cancer stem-like cells; photodynamic therapy; prostate cancer; radiotherapy