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FEBS Lett. 2019 Aug 30. doi: 10.1002/1873-3468.13589. [Epub ahead of print]

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

Author information

1
Cancer Research Unit, Department of Biology, University of York, UK.
2
Department of Physics, York Plasma Institute, University of York, UK.
3
Faculty of Biological Sciences, University of Leeds, UK.
4
Department of Urology, Castle Hill Hospital (Hull and East Yorkshire Hospitals NHS Trust), Cottingham, UK.

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.

KEYWORDS:

Low temperature plasma; Notch signalling; Therapy resistance; progenitor cells; prostate cancer; reactive oxygen species

PMID:
31468514
DOI:
10.1002/1873-3468.13589

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