Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells, "Beyond the Abstract," by Adam Hirst

BERKELEY, CA (UroToday.com) - For many patients with early-diagnosed, low-risk prostate cancer, active surveillance can be an uncomfortable treatment option for those who wish to take action. However, localized disease is often over-treated by radical surgery, with numerous associated side effects. Focal therapies, which aim to eliminate tumours whilst sparing as much healthy tissue as possible, are becoming an increasingly attractive treatment option for patients with unifocal, low-grade prostate cancer. Our review paper evaluates the effectiveness of several current focal therapies, as well as introducing and highlighting the potential of a new treatment concept known as low-temperature plasma.[1] Several focal therapy treatment modalities exist for prostate cancer, including (but not limited to) high-intensity focused ultrasound (HIFU), cryotherapy, photodynamic therapy, and (although not strictly ‘focal’) radiotherapy.[2] The two former modalities utilize thermal effects to induce necrotic cell death, whereas the latter two options rely predominantly on the production of reactive oxygen species to damage DNA and provoke a cytocidal response. Each of these options has its merits, but each also has associated issues, for example unpleasant side effects or damage to healthy tissues. It is on this basis that we believe a new, targeted treatment approach is necessary.

Plasmas exist naturally in many forms including lightning, the aurora borealis, and the Sun. They are by far the most abundant state of matter in the universe. The exotic properties of plasmas has led to their implementation in many different and varied areas such as microprocessing chips for computing and mobile phones, fluorescent lighting tubes, televisions, modification of textile surfaces, and scratch-resistant coatings for glasses. Current research also focuses on the use of plasmas for clean energy, space propulsion technologies, and more recently in the field of biomedicine.

Low temperature plasmas (LTPs) can be ignited at atmospheric pressure and room temperature, generating electric fields, photons, charged particles, and a plethora of reactive oxygen and nitrogen species (RONS).[3] LTPs have already shown considerable efficacy in the treatment of bacteria and the removal of biofilms. They have also been observed to induce responses in eukaryotic cells, both in terms of proliferation (for accelerated wound healing), and cell death (for cancer treatment). It is now widely believed that the transfer of LTP-induced RONS to the treated area is primarily responsible for cellular effects, although synergies with other LTP-facets such as electric fields will likely also play a key role.

Since the publication of our review paper, we now know from our research that LTP induces high levels of DNA damage in both prostate cell lines and primary cells cultured directly from patient tissue samples.[4] This leads to a reduction in viability, and ultimately very few cells recover to form self-sustaining colonies.[5] Plasma treatment led to high concentrations of hydrogen peroxide formation in the cell culture media, which is known to be highly toxic to cells. We determined that the mechanism of cell death was necrosis; which poses the question of whether there may be an associated immune response following treatment, as has been documented following other therapies. Interestingly, LTP-treated cell lines showed some evidence of apoptotic activity, whereas primary cells cultured from patient tissue died via necrosis only. This demonstrates both the need to study close-to-patient samples to gain insight into mechanistic response, and the promise of LTP as a focal therapy modality of the future.

However, for such a treatment to become a reality, a means of plasma-patient application must be developed. In our review paper, we speculatively outlined a transperineal approach to LTP treatment of the prostate, derived from current methods in cryo- and photodynamic therapies. This, combined with real time imaging, could allow for highly targeted, effective eradication of localized cancerous lesions.

References:

  1. Hirst AM, Frame FM, Maitland NJ, O'Connell D. Low Temperature Plasma: A Novel Focal Therapy for Localized Prostate Cancer? BioMed Research International. 2014;2014:878319. PubMed PMID: 24738076. Pubmed Central PMCID: 3971493.
  2. Valerio M, Emberton M, Barret E, Eberli D, Eggener SE, Ehdaie B, et al. Health technology assessment in evolution - focal therapy in localised prostate cancer. Expert Review of Anticancer Therapy. 2014 Nov;14(11):1359-67. PubMed PMID: 24965212.
  3. Graves DB. Reactive Species from Cold Atmospheric Plasma: Implications for Cancer Therapy. Plasma Process Polym. 2014.
  4. Hirst AM, Frame FM, Maitland NJ, O'Connell D. Low Temperature Plasma Causes Double-Strand Break DNA Damage in Primary Epithelial Cells Cultured From a Human Prostate Tumor. Plasma Science, IEEE Transactions on. 2014;42(10):2740-1.
  5. Hirst AM, Simms MS, Mann VM, Maitland NJ, O'Connell D, Frame FM. Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells. Br J Cancer. 2015 Apr 28;112(9):1536-45. PubMed PMID: 25839988.

Written by:
Adam Hirst as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

York Plasma Institute, Department of Physics, University of York, Heslington, York YO10 5DD, United Kingdom

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

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