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

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

Authors

Fiona M. Frame

Huguette Savoie

Francesca Bryden

Francesca Giuntini

Vincent M. Mann

Matthew S. Simms

Ross W. Boyle

Norman J. Maitland



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.

Citation

Frame, F. M., Savoie, H., Bryden, F., Giuntini, F., Mann, V. M., Simms, M. S., …Maitland, N. J. (2016). Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy including senscence, necrosis, and autophagy, but not apoptosis. Cancer medicine, 5(1), 61-73. https://doi.org/10.1002/cam4.553

Journal Article Type Article
Acceptance Date Sep 4, 2015
Online Publication Date Nov 21, 2015
Publication Date 2016-01
Deposit Date Dec 16, 2015
Publicly Available Date Nov 23, 2017
Journal Cancer medicine
Electronic ISSN 2045-7634
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 5
Issue 1
Pages 61-73
DOI https://doi.org/10.1002/cam4.553
Keywords Cancer stem-like cells, Photodynamic therapy, Prostate cancer, Radiotherapy
Public URL https://hull-repository.worktribe.com/output/382918
Publisher URL http://onlinelibrary.wiley.com/doi/10.1002/cam4.553/abstract
Copyright Statement © 2015 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Additional Information This is an open access article published in Cancer medicine, 2015.

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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
© 2015 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.





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