Journal Article

Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy include senescence, necrosis, and autophagy, but not apoptosis

Bryden, Francesca, Maitland, Norman J., Boyle, Ross W., Giuntini, Francesca, Mann, Vincent M., Frame, Fiona M., Savoie, Huguette, Simms, Matthew S.

2016

Overview

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. We determined the consequences of radiotherapy and photodynamic therapy on primary prostate epithelial cells cultured from patient tissue. Photodynamic therapy induced autophagy and necrosis, whereas radiotherapy induced senescence and neither treatment induced apoptosis. This provides evidence that photodynamic therapy could be used in combination with radiotherapy to overcome radio‐recurrent disease.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Apoptosis / Apoptosis - drug effects / Apoptosis - radiation effects / Autophagy / Autophagy - drug effects / Autophagy - radiation effects / Cancer Biology / Cancer stem‐like cells / Cancer therapies / Cell differentiation / Cell Proliferation - radiation effects / Cell Survival - drug effects / Cell Survival - radiation effects / Cell viability / Cells, Cultured / Cellular Senescence - drug effects / Cellular Senescence - radiation effects / Colonies / Cytotoxicity / Deoxyribonucleic acid / DNA / DNA damage / DNA Damage - drug effects / DNA Damage - radiation effects / Epithelial cells / Epithelial Cells - metabolism / Epithelial Cells - radiation effects / Ethics / Gamma Rays - adverse effects / Growth inhibition / Humans / Hyperplasia / Immunofluorescence / Male / Medical research / Necrosis / Original Research / Oxidative Stress - genetics / Patients / Phagocytosis / Photochemotherapy / Photodynamic therapy / Photosensitizing Agents - pharmacology / Population / Propidium iodide / Prostate - cytology / Prostate cancer / Prostatic Neoplasms - metabolism / Prostatic Neoplasms - pathology / Prostatic Neoplasms - therapy / Radiation therapy / radiotherapy / Reactive oxygen species / Reactive Oxygen Species - metabolism / Senescence / Stem Cells / Tumors / Western blotting / β-Galactosidase