Eda Gjika , Sonali Pal-Ghosh , Li Lin , Gauri Tadvalkar , Zhitong Chen , Colin Young , Jerome Canady , Jonathan Sherman , Mary Ann Stepp , Michael Keidar
{"title":"Adaptation Of Operational Parameters Of Cold Atmospheric Plasma And Their Role In Cancer Therapy","authors":"Eda Gjika , Sonali Pal-Ghosh , Li Lin , Gauri Tadvalkar , Zhitong Chen , Colin Young , Jerome Canady , Jonathan Sherman , Mary Ann Stepp , Michael Keidar","doi":"10.1016/j.cpme.2017.12.026","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>The evaluation of CAP in cancer treatment has been significantly fueled by the growing demand for more effective therapies. CAP has been reported as a selective treatment method with a higher affinity of inducing </span>cell death in </span>cancer cells<span><span> while leaving normal cells unharmed. However, the extent of its effectiveness varies significantly per cancer type. Studies have revealed that different types of cancers exhibit different response to treatment when exposed to the same CAP conditions. Therefore, an understanding of the immediate effect of CAP on cancer cells may enable improvement of treatment outcomes [1]. We demonstrated that instantaneous CAP response can be monitored in real-time by RealTime-Glo Assay with results interpreted as </span>cell viability. This creates the possibility for developing an adaptive CAP approach platform which could enable real-time modification of the plasma treatment condition. In particular, the composition of reactive oxygen and nitrogen species (RONS) and the intensity of CAP, which is effected by discharge voltage and length of treatment, can be optimized with a feedback system at regular intervals to minimize the predicted viability of cancer cells [1, 2].</span></p><p>In an <em>in vitro</em><span> proof-of-concept study conducted in glioblastoma<span> and breast cancer cells, we showed that CAP reduced cell viability in a dose dependent manner as a function of treatment duration and plasma discharge voltage. In fact, a 30-60 second increase in treatment duration and/or a discharge voltage adjustment from 3.16 to 3.71 kV, was consistently accompanied with a significant reduction in cell viability. Therefore, these two operational parameters can be utilized for adjusting plasma composition and improving treatment outcomes. In addition to the cell viability findings, we determined that CAP inhibited cancer cell proliferation and triggered apoptosis via damage to the mitochondrial membrane<span> and deregulation of the protein synthesis mechanism [2]. The work completed in this study will serve as the foundation for the development of the adaptive CAP platform. The novel platform will intend to propel CAP therapy forefront other well-established therapies associated with cancer treatment.</span></span></span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.026","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Plasma Medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212816617300513","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 4
Abstract
The evaluation of CAP in cancer treatment has been significantly fueled by the growing demand for more effective therapies. CAP has been reported as a selective treatment method with a higher affinity of inducing cell death in cancer cells while leaving normal cells unharmed. However, the extent of its effectiveness varies significantly per cancer type. Studies have revealed that different types of cancers exhibit different response to treatment when exposed to the same CAP conditions. Therefore, an understanding of the immediate effect of CAP on cancer cells may enable improvement of treatment outcomes [1]. We demonstrated that instantaneous CAP response can be monitored in real-time by RealTime-Glo Assay with results interpreted as cell viability. This creates the possibility for developing an adaptive CAP approach platform which could enable real-time modification of the plasma treatment condition. In particular, the composition of reactive oxygen and nitrogen species (RONS) and the intensity of CAP, which is effected by discharge voltage and length of treatment, can be optimized with a feedback system at regular intervals to minimize the predicted viability of cancer cells [1, 2].
In an in vitro proof-of-concept study conducted in glioblastoma and breast cancer cells, we showed that CAP reduced cell viability in a dose dependent manner as a function of treatment duration and plasma discharge voltage. In fact, a 30-60 second increase in treatment duration and/or a discharge voltage adjustment from 3.16 to 3.71 kV, was consistently accompanied with a significant reduction in cell viability. Therefore, these two operational parameters can be utilized for adjusting plasma composition and improving treatment outcomes. In addition to the cell viability findings, we determined that CAP inhibited cancer cell proliferation and triggered apoptosis via damage to the mitochondrial membrane and deregulation of the protein synthesis mechanism [2]. The work completed in this study will serve as the foundation for the development of the adaptive CAP platform. The novel platform will intend to propel CAP therapy forefront other well-established therapies associated with cancer treatment.