Plasma-activated Ringer’s Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells

Epithelial Ovarian Cancer (EOC) is one of the leading causes of cancer-related deaths among women and is characterized by the diffusion of nodules or plaques from the ovary to the peritoneal surfaces. Conventional therapeutic options cannot eradicate the disease and show low efficacy against resistant tumor subclones. The treatment of liquids via cold atmospheric pressure plasma enables the production of plasma-activated liquids (PALs) containing reactive oxygen and nitrogen species (RONS) with selective anticancer activity. Thus, the delivery of RONS to cancer tissues by intraperitoneal washing with PALs might be an innovative strategy for the treatment of EOC. In this work, plasma-activated Ringer’s Lactate solution (PA-RL) was produced by exposing a liquid substrate to a multiwire plasma source. Subsequently, PA-RL dilutions are used for the treatment of EOC, non-cancer and fibroblast cell lines, revealing a selectivity of PA-RL, which induces a significantly higher cytotoxic effect in EOC with respect to non-cancer cells.

[1]  M. Mizuno,et al.  Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions , 2019, Scientific Reports.

[2]  S. Dewilde,et al.  The Influence of Cell Type and Culture Medium on Determining Cancer Selectivity of Cold Atmospheric Plasma Treatment , 2019, Cancers.

[3]  M. Laroussi Effects of PAM on select normal and cancerous epithelial cells , 2019, Plasma Research Express.

[4]  A. Oza,et al.  Epithelial ovarian cancer , 2019, The Lancet.

[5]  Xiaodong Cheng,et al.  Efficacy of hyperthermic intraperitoneal chemotherapy in patients with epithelial ovarian cancer: a meta-analysis , 2019, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[6]  M. Janda,et al.  Chemical and antibacterial effects of plasma activated water: correlation with gaseous and aqueous reactive oxygen and nitrogen species, plasma sources and air flow conditions , 2018, Journal of Physics D: Applied Physics.

[7]  V. Colombo,et al.  Cold Atmospheric Pressure Plasma Treatment Modulates Human Monocytes/Macrophages Responsiveness , 2018, Plasma.

[8]  T. Adachi,et al.  Enhanced ability of plasma-activated lactated Ringer's solution to induce A549 cell injury. , 2018, Archives of biochemistry and biophysics.

[9]  Eun Ha Choi,et al.  Biological and medical applications of plasma-activated media, water and solutions , 2018, Biological chemistry.

[10]  D. Khabele,et al.  Heated Intraperitoneal Chemotherapy in the Management of Advanced Ovarian Cancer , 2018, Cancers.

[11]  T. von Woedtke,et al.  The kINPen—a review on physics and chemistry of the atmospheric pressure plasma jet and its applications , 2018 .

[12]  G. Kenter,et al.  Development of Peritoneal Carcinomatosis in Epithelial Ovarian Cancer: A Review , 2018, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[13]  N. Aaronson,et al.  Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer , 2018, The New England journal of medicine.

[14]  C. Canal,et al.  Plasma‐induced selectivity in bone cancer cells death , 2017, Free radical biology & medicine.

[15]  M. Mizuno,et al.  Novel Intraperitoneal Treatment With Non-Thermal Plasma-Activated Medium Inhibits Metastatic Potential of Ovarian Cancer Cells , 2017, Scientific Reports.

[16]  J. Jimenez-Heffernan,et al.  Mesothelial‐to‐mesenchymal transition as a possible therapeutic target in peritoneal metastasis of ovarian cancer , 2017, The Journal of pathology.

[17]  Thomas A. Sellers,et al.  Epidemiology of ovarian cancer: a review , 2017, Cancer biology & medicine.

[18]  M. Kanda,et al.  Intraperitoneal Administration of Plasma-Activated Medium: Proposal of a Novel Treatment Option for Peritoneal Metastasis From Gastric Cancer , 2017, Annals of Surgical Oncology.

[19]  G. Scambia,et al.  Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases , 2016, Annals of Surgical Oncology.

[20]  M. Mizuno,et al.  Non-thermal atmospheric pressure plasma activates lactate in Ringer’s solution for anti-tumor effects , 2016, Scientific Reports.

[21]  T. Kondo,et al.  Cell survival of glioblastoma grown in medium containing hydrogen peroxide and/or nitrite, or in plasma-activated medium. , 2016, Archives of biochemistry and biophysics.

[22]  V. Víctor,et al.  Role of ROS and RNS Sources in Physiological and Pathological Conditions , 2016, Oxidative medicine and cellular longevity.

[23]  M. Mizuno,et al.  Possible therapeutic option of aqueous plasma for refractory ovarian cancer , 2016 .

[24]  Navdeep S. Chandel,et al.  Fundamentals of cancer metabolism , 2016, Science Advances.

[25]  M. Mizuno,et al.  Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium , 2016, Oncology reports.

[26]  Yen-Hou Chang,et al.  Front-line intraperitoneal versus intravenous chemotherapy in stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease: a competing risk analysis , 2016, BMC Cancer.

[27]  Stephen T. C. Wong,et al.  Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis. , 2015, American journal of physiology. Cell physiology.

[28]  B. Monk,et al.  Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a gynecologic oncology group study. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  Jaime Prat,et al.  FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum: abridged republication , 2015, Journal of gynecologic oncology.

[30]  G. Tonini,et al.  Ovarian cancer standard of care: are there real alternatives? , 2015, Chinese journal of cancer.

[31]  David B. Graves,et al.  Reactive Species from Cold Atmospheric Plasma: Implications for Cancer Therapy , 2014 .

[32]  Bernd Holleczek,et al.  Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study. , 2014, The Lancet. Oncology.

[33]  Hiromasa Tanaka,et al.  Selective cytotoxicity of indirect nonequilibrium atmospheric pressure plasma against ovarian clear-cell carcinoma , 2014, SpringerPlus.

[34]  M. Mizuno,et al.  Effect of Indirect Nonequilibrium Atmospheric Pressure Plasma on Anti-Proliferative Activity against Chronic Chemo-Resistant Ovarian Cancer Cells In Vitro and In Vivo , 2013, PloS one.

[35]  P. Lukeš,et al.  Elementary Chemical and Physical Phenomena in Electrical Discharge Plasma in Gas–Liquid Environments and in Liquids , 2012 .

[36]  David B. Graves,et al.  The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology , 2012 .

[37]  M. Hori,et al.  Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma , 2012 .

[38]  Peng Huang,et al.  Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? , 2009, Nature Reviews Drug Discovery.

[39]  Binjie Dong,et al.  Experimental study of a DBD surface discharge for the active control of subsonic airflow , 2008 .

[40]  C. Le Page,et al.  Characterization of ovarian cancer ascites on cell invasion, proliferation, spheroid formation, and gene expression in an in vitro model of epithelial ovarian cancer. , 2007, Neoplasia.

[41]  M. Šimek,et al.  Time and space resolved analysis of N 2 (C 3 Π u ) vibrational distributions in pulsed positive corona discharge , 2002 .

[42]  L. Yoder The epidemiology of ovarian cancer: a review. , 1990, Oncology nursing forum.

[43]  P. Bourke,et al.  Achieving reactive species specificity within plasma‐activated water through selective generation using air spark and glow discharges , 2017 .

[44]  S. Yamada,et al.  Effect of Plasma-Activated Lactated Ringer’s Solution on Pancreatic Cancer Cells In Vitro and In Vivo , 2017, Annals of Surgical Oncology.