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.
Highlights
Low Temperature Plasma (LTP) generates reactive oxygen and nitrogen species, causing cell death, to radiation
FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
LTP induces an oxidative stress response in primary prostate basal epithelial cultures To assess the cellular reaction to LTP, we assembled a panel of primary prostate epithelial cultures from normal (n = 3), benign (n = 3) and malignant tissue [Gleason 7 (G7) (n = 3) and Gleason 9 (G9)(n = 3)] and analysed the expression of 84 genes at 2 h following a 3-min LTP dose, using Qiagen Oxidative Stress Profiler Arrays (Fig. 1B–E)
Summary
Low Temperature Plasma (LTP) generates reactive oxygen and nitrogen species, causing cell death, to radiation. Mixing of LTP with gas molecules in the air produces high concentrations of reactive oxygen and nitrogen species (ROS and RNS) [2,3] that can cause oxidative stress, DNA damage [1,2] protein oxidation [5] and lipid peroxidation in cells [5]. LTP-based treatment of cancer cells is being considered for a variety of malignancies [6], including prostate cancer [1] Before this mode of treatment can be developed for clinical use, the full mechanism of action, and potential mechanisms of resistance, needs to be elucidated. Abbreviations ADT, androgen-deprivation therapy; CB, committed basal; LTP, low temperature plasma; PAP, prostatic acid phosphatase; qRT-PCR, quantitative reverse transcription PCR; RNS, reactive nitrogen species; ROS, reactive oxygen species; SC, stem cell; TA, transit amplifying. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
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