Anticancer Effect of Cold Atmospheric Plasma in Syngeneic Mouse Models of Melanoma and Colon Cancer

Cold atmospheric plasma (CAP) may have applications in treating various types of malignant tumors. This study assessed the anticancer effects of CAP using melanoma and colon cancer cell lines. CAP treatment significantly reduced the in vitro viability of melanoma and colon cancer cell lines and had a negligible effect on the viability of normal human melanocytes. Additionally, CAP and epidermal growth factor receptor (EGFR) inhibitor had an additive anticancer effect in a CAP-resistant melanoma cell line. Reactive oxygen and nitrogen species known to be generated by CAP enhanced the anticancer effects of CAP and EGFR inhibitors. The in vivo anticancer activities of CAP were evaluated by testing its effects against syngeneic tumors induced in mice by melanoma and colon cancer cells. CAP treatment reduced tumor volume and weight in both cancer models, with the extent of tumor reduction dependent on the duration and number of CAP treatments. Histologic examination also revealed the tumoricidal effects of CAP in both tumor models. In conclusion, CAP inhibits the growth of mouse melanoma and colon cancer cell lines in vitro and shows tumoricidal effects against mouse models of melanoma and colon cancer in vivo.

[1]  S. Chang,et al.  Prognostic Significance of Epidermal Growth Factor Receptor Expression in Distant Metastatic Melanoma from Primary Cutaneous Melanoma , 2021, Annals of dermatology.

[2]  S. Chang,et al.  Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models , 2021, The international journal of lower extremity wounds.

[3]  T. von Woedtke,et al.  Tumor cell metabolism correlates with resistance to gas plasma treatment: the evaluation of three dogmas. , 2021, Free radical biology & medicine.

[4]  S. Chang,et al.  Different progression pattern between acral and nonacral melanoma: A retrospective, comparative, clinicoprognostic study of 492 cases of primary cutaneous melanoma according to tumor site. , 2021, Indian journal of dermatology, venereology and leprology.

[5]  S. Chang,et al.  Lymphatic invasion in acral and non-acral melanoma: a comparative, clinicoprognostic study of primary cutaneous melanoma according to tumour site. , 2020, Pathology.

[6]  E. Gonzalez-Sanchez,et al.  Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma , 2020, Cancers.

[7]  C. Canal,et al.  Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma , 2020, Cancers.

[8]  James R. Anderson,et al.  Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. , 2019, The Lancet. Oncology.

[9]  S. Laurencin-Dalicieux,et al.  Use of cold-atmospheric plasma in oncology: a concise systematic review , 2018, Therapeutic advances in medical oncology.

[10]  I. Moon,et al.  Review of the Current State of Medical Plasma Technology and its Potential Applications , 2018, Medical Lasers.

[11]  E. Choi,et al.  Clinical experience with cold plasma in the treatment of locally advanced head and neck cancer , 2018 .

[12]  Jeffrey E Gershenwald,et al.  Melanoma staging: Evidence‐based changes in the American Joint Committee on Cancer eighth edition cancer staging manual , 2017, CA: a cancer journal for clinicians.

[13]  Jun‐Seok Oh,et al.  Tracking the Penetration of Plasma Reactive Species in Tissue Models. , 2017, Trends in biotechnology.

[14]  P. Milkiewicz,et al.  Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis , 2017, Scientific Reports.

[15]  A. Bogaerts,et al.  Hampering Effect of Cholesterol on the Permeation of Reactive Oxygen Species through Phospholipids Bilayer: Possible Explanation for Plasma Cancer Selectivity , 2017, Scientific Reports.

[16]  M. Keidar,et al.  Cold atmospheric plasma, a novel promising anti-cancer treatment modality , 2016, Oncotarget.

[17]  Ngoc Hoan Nguyen,et al.  Anti-cancer efficacy of nonthermal plasma dissolved in a liquid, liquid plasma in heterogeneous cancer cells , 2016, Scientific Reports.

[18]  Kyoung-Nam Kim,et al.  Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma , 2016, PloS one.

[19]  T. H. Chung,et al.  Cold atmospheric plasma jet-generated RONS and their selective effects on normal and carcinoma cells , 2016, Scientific Reports.

[20]  M. Keidar,et al.  Toward understanding the selective anticancer capacity of cold atmospheric plasma--a model based on aquaporins (Review). , 2015, Biointerphases.

[21]  N. Sang,et al.  Uniform Nanosecond Pulsed Dielectric Barrier Discharge Plasma Enhances Anti‐Tumor Effects by Induction of Immunogenic Cell Death in Tumors and Stimulation of Macrophages , 2015 .

[22]  D. Rodrigues,et al.  Reaction Chemistry Generated by Nanosecond Pulsed Dielectric Barrier Discharge Treatment is Responsible for the Tumor Eradication in the B16 Melanoma Mouse Model. , 2015, Plasma processes and polymers.

[23]  M. Papadopoulos,et al.  Key roles of aquaporins in tumor biology. , 2015, Biochimica et biophysica acta.

[24]  D. Leffell,et al.  Melanoma in situ: Part II. Histopathology, treatment, and clinical management. , 2015, Journal of the American Academy of Dermatology.

[25]  R. Walther,et al.  Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways , 2015, PloS one.

[26]  M. Keidar,et al.  Effect of Cold Plasma on Glial Cell Morphology Studied by Atomic Force Microscopy , 2015, PloS one.

[27]  Ulrich Keilholz,et al.  Expression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway , 2015, Targeted Oncology.

[28]  M. M. Evans,et al.  Atmospheric pressure gas plasma-induced colorectal cancer cell death is mediated by Nox2-ASK1 apoptosis pathways and oxidative stress is mitigated by Srx-Nrf2 anti-oxidant system. , 2014, Biochimica et biophysica acta.

[29]  Vandana Miller,et al.  Plasma Stimulation of Migration of Macrophages: Plasma Stimulation of Migration … , 2014 .

[30]  Sun Ja Kim,et al.  Production of intracellular reactive oxygen species and change of cell viability induced by atmospheric pressure plasma in normal and cancer cells , 2013 .

[31]  M. Keidar,et al.  Cold Atmospheric Plasma for Selectively Ablating Metastatic Breast Cancer Cells , 2013, PloS one.

[32]  Q. Ma.  Role of nrf2 in oxidative stress and toxicity. , 2013, Annual review of pharmacology and toxicology.

[33]  A. Kramer,et al.  Tissue Tolerable Plasma (TTP) induces apoptosis in pancreatic cancer cells in vitro and in vivo , 2012, BMC Cancer.

[34]  M. Keidar,et al.  Targeting the cancer cell cycle by cold atmospheric plasma , 2012, Scientific Reports.

[35]  J. Zirnheld,et al.  Preferential induction of apoptotic cell death in melanoma cells as compared with normal keratinocytes using a non-thermal plasma torch , 2012, Cancer biology & therapy.

[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]  John Ballato,et al.  Apoptosis of lung carcinoma cells induced by a flexible optical fiber-based cold microplasma. , 2011, Biosensors & bioelectronics.

[38]  Jo Lambert,et al.  EGFR in melanoma: clinical significance and potential therapeutic target , 2011, Journal of cutaneous pathology.

[39]  T. Mak,et al.  Regulation of cancer cell metabolism , 2011, Nature Reviews Cancer.

[40]  J. Pouvesle,et al.  Experimental Study of a Compact Nanosecond Plasma Gun , 2009 .

[41]  R. Ádány,et al.  EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis , 2007, International journal of cancer.

[42]  B. Teicher.  Tumor models for efficacy determination , 2006, Molecular Cancer Therapeutics.

[43]  B. Cookson,et al.  Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells , 2005, Infection and Immunity.

[44]  Henning Walczak,et al.  The interplay between the Bcl-2 family and death receptor-mediated apoptosis. , 2004, Biochimica et biophysica acta.

[45]  A. Porter,et al.  Emerging roles of caspase-3 in apoptosis , 1999, Cell Death and Differentiation.

[46]  J. Platt,et al.  Heme oxygenase: Protective gene or Trojan horse , 1998, Nature Medicine.

[47]  C. Won,et al.  Cold Atmospheric Plasma Prevents Wrinkle Formation via an Antiaging Process , 2020 .

[48]  Vandana Miller,et al.  Why Target Immune Cells for Plasma Treatment of Cancer , 2015, Plasma Chemistry and Plasma Processing.