4.7 Article

Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells

Journal

BRITISH JOURNAL OF CANCER
Volume 112, Issue 9, Pages 1536-1545

Publisher

SPRINGERNATURE
DOI: 10.1038/bjc.2015.113

Keywords

low-temperature plasma; necrosis; primary epithelial cells; prostate cancer; reactive species

Categories

Funding

  1. Wellcome Trust [097829/Z/11/A]
  2. UK EPSRC [EP/H003797/1, EP/K018388/1]
  3. Yorkshire Cancer Research (Frame, Maitland) [YCR - Y257PA]
  4. EPSRC [EP/K018388/1, EP/H003797/2, EP/H003797/1, EP/I500987/1] Funding Source: UKRI
  5. Wellcome Trust [097829/Z/11/A] Funding Source: Wellcome Trust
  6. Engineering and Physical Sciences Research Council [EP/I500987/1, EP/H003797/2, EP/H003797/1, EP/K018388/1, 1225063] Funding Source: researchfish

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Background: In recent years, the rapidly advancing field of low-temperature atmospheric pressure plasmas has shown considerable promise for future translational biomedical applications, including cancer therapy, through the generation of reactive oxygen and nitrogen species. Method: The cytopathic effect of low-temperature plasma was first verified in two commonly used prostate cell lines: BPH-1 and PC-3 cells. The study was then extended to analyse the effects in paired normal and tumour (Gleason grade 7) prostate epithelial cells cultured directly from patient tissue. Hydrogen peroxide (H2O2) and staurosporine were used as controls throughout. Results: Low-temperature plasma (LTP) exposure resulted in high levels of DNA damage, a reduction in cell viability, and colony-forming ability. H2O2 formed in the culture medium was a likely facilitator of these effects. Necrosis and autophagy were recorded in primary cells, whereas cell lines exhibited apoptosis and necrosis. Conclusions: This study demonstrates that LTP treatment causes cytotoxic insult in primary prostate cells, leading to rapid necrotic cell death. It also highlights the need to study primary cultures in order to gain more realistic insight into patient response.

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