This study reports the experimental findings and plasma delivery approach developed

This study reports the experimental findings and plasma delivery approach developed at the Plasma Bioscience Research Center Korea for the assessment of antitumor activity of dielectric barrier discharge (DBD) for cancer treatment. with APNT DBD plasma and cellular effects due to reactive oxygen species were observed. Plasma significantly decreased the metabolic viability and clonogenicity of T98G SNU80 KB and HEK293 TAK-733 cell lines. Enhanced ROS in the cells led to death via alteration of total antioxidant activity and NADP+/NADPH and GSH/GSSG ratios 24 hours (h) post plasma treatment. This effect was confirmed by annexin V-FITC and propidium iodide staining. These consequences suggested that the failure of antioxidant defense machinery with compromised redox status might have led to sensitization TAK-733 of the malignant cells. These findings suggest a promising approach for solid tumor therapy by delivering a lethal dose of APNT plasma to tumor cells while sparing normal healthy tissues. Background Cancer TAK-733 is the foremost cause of increasing human death in economically developed countries [1]. Chemotherapy [2] and TAK-733 photodynamic therapy [3] are frequently applied in cancer therapy to eradicate tumor cells for maximum treatment efficacy but they also cause side effects that influence normal healthy cells. The use of radiotherapy is only 40% effective if used prior to surgery [4]. Although medical science has progressively improved treatment techniques to cure cancer treatment approaches are still imperfect [5] due to inadequate drug distribution dose limiting toxicity and poor cancer cell selectivity. Nevertheless even with many advances in chemotherapy and radiotherapy survival rates have persistently decreased over the past years. Hence a new cancer treatment modality is required to improve survival rates. The use of non-thermal atmospheric-pressure plasma has recently expanded into Eng biomedical fields (a research area called ‘plasma medicine’) [6]. Plasma sources usually contain a mixture of charged particles radicals (e.g. reactive oxygen species (ROS)) and other reactive molecules (e.g. hydrogen peroxide nitric oxide) as well as photons (UV). Free radicals play a big role in cellular redox signaling pathways but high levels of ROS can have adverse effects on cells and lead to activation of cellular apoptotic pathways. Recently our group reported valuable effects of non-thermal plasma on cancer cell death [7]. Several reports on the application of plasma for treatment of cancer were limited to a few types of cancer targets [8]-[16] which is not sufficient to establish nonthermal plasma effects on every type of cancer. Different types of cancer cell lines may have different responses to the same treatment therapies. Plasma-induced cancer cell death seems to be dependent on cellular ROS pathways [17]. Some researchers claim that ROS induced by anticancer drugs produce a shift in cellular antioxidant machinery [18] [19] and in mitochondrial membrane potential which is related to induction of programmed cell death (apoptosis) in cancer cells [20] [21]. Herein we report on APNT plasma interaction with three tumor cell lines human glioblastoma cells (T98G) thyroid carcinoma cells (SNU80) and oral carcinoma cells (KB) and a non-malignant embryonic cells (HEK293). It is crucial to explore the interactions between the production of plasma-induced reactive species and cellular responses. While plasma-mediated oxidative stress may bring about harmful or beneficial cellular responses one should examine carefully the plasma-dependent effects within target cells by comparing the effects on cancer and normal cells [22]. Previously we reported that plasma-induced cell death in T98G brain cancer cells and have the least toxic effect on non-malignant HEK293 cells [23]. This additional study was designed to explore the role of ROS sensitive antioxidant machinery against the APNT DBD plasma induced oxidative stress in different cancer cells. Materials and Methods Human cell lines The human cancer cell lines glioblastoma (T98G) thyroid carcinoma (SNU80) oral carcinoma (KB) and non-malignant embryonic cells (HEK293) were acquired from the KCLB (Korean Cell Line Bank Seoul Korea). For the plasma-cell interaction these cells were maintained in Dulbecco’s Modified Eagle Medium (Hyclone USA) supplemented with 10% fetal bovine serum (Hyclone USA) and 1% TAK-733 penicillin-streptomycin (PS) at 37°C in a humidified atmosphere of 5% CO2. Experimental device specifications and TAK-733 plasma treatment Atmospheric pressure non-thermal (APNT) DBD plasma was designed and used to provide uniform treatment for biomedical.