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Notch signalling is a potential resistance mechanism of progenitor cells within patient‐derived prostate cultures following ROS‐inducing treatments

Packer, John R.; Hirst, Adam M.; Droop, Alastair P.; Adamson, Rachel; Simms, Matthew S.; Mann, Vincent M.; Frame, Fiona M.; O'Connell, Deborah; Maitland, Norman J.

Authors

John R. Packer

Adam M. Hirst

Alastair P. Droop

Rachel Adamson

Matthew S. Simms

Vincent M. Mann

Deborah O'Connell

Norman J. Maitland



Abstract

Low Temperature Plasma (LTP) generates reactive oxygen and nitrogen species, causing cell death, similarly to radiation. Radiation resistance results in tumour recurrence, however mechanisms of LTP resistance are unknown. LTP was applied to patient‐derived prostate epithelial cells and gene expression assessed. A typical global oxidative response (AP‐1 and Nrf2 signalling) was induced, whereas Notch signalling was activated exclusively in progenitor cells. Notch inhibition induced expression of prostatic acid phosphatase (PAP), a marker of prostate epithelial cell differentiation, whilst reducing colony forming ability and preventing tumour formation. Therefore, if LTP is to be progressed as a novel treatment for prostate cancer, combination treatments should be considered in the context of cellular heterogeneity and existence of cell type‐specific resistance mechanisms.

Journal Article Type Article
Publication Date Aug 30, 2019
Journal FEBS Letters
Print ISSN 0014-5793
Electronic ISSN 1873-3468
Publisher Wiley
Peer Reviewed Peer Reviewed
APA6 Citation Packer, J. R., Hirst, A. M., Droop, A. P., Adamson, R., Simms, M. S., Mann, V. M., …Maitland, N. J. (2019). Notch signalling is a potential resistance mechanism of progenitor cells within patient‐derived prostate cultures following ROS‐inducing treatments. FEBS Letters, https://doi.org/10.1002/1873-3468.13589
DOI https://doi.org/10.1002/1873-3468.13589
Keywords Low temperature plasma; Notch signalling; Progenitor cells; Prostate cancer; Reactive oxygen species; Therapy resistance
Publisher URL https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.13589
Related Public URLs http://eprints.whiterose.ac.uk/150977/
Additional Information Received: 2019-05-29; Accepted: 2019-08-08; Published: 2019-09-17

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Copyright Statement
© 2019 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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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