PSM America Inc.

Colorado Springs, CO, United States

PSM America Inc.

Colorado Springs, CO, United States
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Kim C.-H.,University of Tennessee at Knoxville | Kim C.-H.,Ajou University | Bahn J.H.,University of Tennessee at Knoxville | Lee S.-H.,University of Tennessee at Knoxville | And 4 more authors.
Journal of Biotechnology | Year: 2010

Plasma is generated by ionizing neutral gas molecules, resulting in a mixture of energy particles, including electrons and ions. Recent progress in the understanding of non-thermal atmospheric plasma has led to applications in biomedicine. However, the exact molecular mechanisms involved in plasma-induced cell growth arrest are unclear. In this study, we investigated the feasibility of non-thermal atmospheric plasma treatment for cancer therapy and examined the mechanism by which plasma induces anti-proliferative properties and cell death in human colorectal cancer cells. Non-thermal atmospheric plasma induced cell growth arrest and induced apoptosis. In addition, plasma reduced cell migration and invasion activities. As a result, we found that plasma treatment to the cells increases β-catenin phosphorylation, suggesting that β-catenin degradation plays a role at least in part in plasma-induced anti-proliferative activity. Therefore, non-thermal atmospheric plasma constitutes a new biologic tool with the potential for therapeutic applications that modulate cell signaling and function. © 2010 Elsevier B.V.


Kim C.-H.,University of Tennessee at Knoxville | Kim C.-H.,Ajou University | Kwon S.,University of Tennessee at Knoxville | Bahn J.H.,University of Tennessee at Knoxville | And 4 more authors.
Applied Physics Letters | Year: 2010

The effect that the gas content and plasma power of atmospheric, nonthermal plasma has on the invasion activity in colorectal cancer cells has been studied. Helium and helium plus oxygen plasmas were induced through a nozzle and operated with an ac power of less than 10 kV which exhibited a length of 2.5 cm and a diameter of 3-4 mm in ambient air. Treatment of cancer cells with the plasma jet resulted in a decrease in cell migration/invasion with higher plasma intensity and the addition of oxygen to the He flow gas. © 2010 American Institute of Physics.


Kang S.U.,Ajou University | Cho J.-H.,Suwon Catholic University | Chang J.W.,Ajou University | Shin Y.S.,Ajou University | And 7 more authors.
Cell Death and Disease | Year: 2014

Nonthermal plasma (NTP) is generated by ionization of neutral gas molecules, which results in a mixture of energy particles including electrons and ions. Recent progress in the understanding of NTP has led to its application in the treatment of various diseases, including cancer. However, the molecular mechanisms of NTP-induced cell death are unclear. The purpose of this study was to evaluate the molecular mechanism of NTP in the induction of apoptosis of head and neck cancer (HNC) cells. The effects of NTP on apoptosis were investigated using MTT, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, Annexin V assays, and western blot analysis. The cells were examined for production of reactive oxygen species (ROS) using DCFCA or MitoSOX staining, intracellular signaling, and an animal model. NTP reduced HNC cell viability in a dosedependent manner and induced apoptosis. NTP resulted in alteration of mitochondrial membrane potential and accumulation of intracellular ROS generated from the mitochondria in HNC cells. Blockade of ROS production by N-acetyl-L-cysteine inhibited NTP-induced apoptosis. NTP led to the phosphorylation of c-JUN N-terminal kinase (JNK) and p38, but not extracellularregulated kinase. Treatment with JNK and p38 inhibitors alleviated NTP-induced apoptosis via ROS generation. Taken together, these results show that NTP induced apoptosis of HNC cells by a mechanism involving MAPK-dependent mitochondrial ROS. NTP inhibited the growth of pre-established FaDu tumors in a nude mouse xenograft model and resulted in accumulation of intracellular ROS. In conclusion, NTP induced apoptosis in HNC cells through a novel mechanism involving MAPK-mediated mitochondrial ROS. These findings show the therapeutic potential of NTP in HNC. © 2014 Macmillan Publishers Limited.


PubMed | Ajou University, Suwon Catholic University and PSM America Inc.
Type: | Journal: Cell death & disease | Year: 2014

Nonthermal plasma (NTP) is generated by ionization of neutral gas molecules, which results in a mixture of energy particles including electrons and ions. Recent progress in the understanding of NTP has led to its application in the treatment of various diseases, including cancer. However, the molecular mechanisms of NTP-induced cell death are unclear. The purpose of this study was to evaluate the molecular mechanism of NTP in the induction of apoptosis of head and neck cancer (HNC) cells. The effects of NTP on apoptosis were investigated using MTT, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, Annexin V assays, and western blot analysis. The cells were examined for production of reactive oxygen species (ROS) using DCFCA or MitoSOX staining, intracellular signaling, and an animal model. NTP reduced HNC cell viability in a dose-dependent manner and induced apoptosis. NTP resulted in alteration of mitochondrial membrane potential and accumulation of intracellular ROS generated from the mitochondria in HNC cells. Blockade of ROS production by N-acetyl-L-cysteine inhibited NTP-induced apoptosis. NTP led to the phosphorylation of c-JUN N-terminal kinase (JNK) and p38, but not extracellular-regulated kinase. Treatment with JNK and p38 inhibitors alleviated NTP-induced apoptosis via ROS generation. Taken together, these results show that NTP induced apoptosis of HNC cells by a mechanism involving MAPK-dependent mitochondrial ROS. NTP inhibited the growth of pre-established FaDu tumors in a nude mouse xenograft model and resulted in accumulation of intracellular ROS. In conclusion, NTP induced apoptosis in HNC cells through a novel mechanism involving MAPK-mediated mitochondrial ROS. These findings show the therapeutic potential of NTP in HNC.


Lee S.Y.,Chung - Ang University | Kang S.U.,Ajou University | Kim K.I.,Ajou University | Kang S.,Ajou University | And 7 more authors.
Yonsei Medical Journal | Year: 2014

Purpose: To determine the effects of nonthermal plasma (NTP) induced by helium (He) alone or He plus oxygen (O2) on the generation of reactive oxygen species (ROS) and cell death in anaplastic thyroid cancer cells.Materials and Methods: NTP was generated in He alone or He plus O2 blowing through a nozzle by applying a high alternating current voltage to the discharge electrodes. Optical emission spectroscopy was used to identify various excited plasma species. The apoptotic effect of NTP on the anaplastic thyroid cancer cell lines, such as HTH83, U-HTH 7, and SW1763, was verified with annexin V/propidium staining and TUNEL assay. ROS formation after NTP treatment was identified with fluorescence-activated cell sorting with DCFDA staining. The mitogen-activated protein kinase pathways and caspase cascade were investigated to evaluate the molecular mechanism involved and cellular targets of plasma.Results: NTP induced significant apoptosis in all three cancer cell lines. The plasma using He and O2 generated more O2-related species, and increased apoptosis and intracellular ROS formation compared with the plasma using He alone. NTP treatment of SW1763 increased the expression of phosphor-JNK, phosphor-p38, and caspase-3, but not phosphor-ERK. Apoptosis of SW1763 as well as expressions of elevated phosphor-JNK, phosphor-p38, and caspase-3 induced by NTP were effectively inhibited by intracellular ROS scavengers.Conclusion: NTP using He plus O2 induced significant apoptosis in anaplastic cancer cell lines through intracellular ROS formation. This may represent a new promising treatment modality for this highly lethal disease. © Yonsei University College of Medicine 2014.


PubMed | Ajou University, PSM America Inc. and Chung - Ang University
Type: Journal Article | Journal: Yonsei medical journal | Year: 2014

To determine the effects of nonthermal plasma (NTP) induced by helium (He) alone or He plus oxygen (O) on the generation of reactive oxygen species (ROS) and cell death in anaplastic thyroid cancer cells.NTP was generated in He alone or He plus O blowing through a nozzle by applying a high alternating current voltage to the discharge electrodes. Optical emission spectroscopy was used to identify various excited plasma species. The apoptotic effect of NTP on the anaplastic thyroid cancer cell lines, such as HTH83, U-HTH 7, and SW1763, was verified with annexin V/propidium staining and TUNEL assay. ROS formation after NTP treatment was identified with fluorescence-activated cell sorting with DCFDA staining. The mitogen-activated protein kinase pathways and caspase cascade were investigated to evaluate the molecular mechanism involved and cellular targets of plasma.NTP induced significant apoptosis in all three cancer cell lines. The plasma using He and O generated more O-related species, and increased apoptosis and intracellular ROS formation compared with the plasma using He alone. NTP treatment of SW1763 increased the expression of phosphor-JNK, phosphor-p38, and caspase-3, but not phosphor-ERK. Apoptosis of SW1763 as well as expressions of elevated phosphor-JNK, phosphor-p38, and caspase-3 induced by NTP were effectively inhibited by intracellular ROS scavengers.NTP using He plus O induced significant apoptosis in anaplastic cancer cell lines through intracellular ROS formation. This may represent a new promising treatment modality for this highly lethal disease.


Chang J.W.,Ajou University | Kang S.U.,Ajou University | Shin Y.S.,Ajou University | Kim K.I.,Ajou University | And 7 more authors.
Archives of Biochemistry and Biophysics | Year: 2014

Recent advances in physics have made possible the use of non-thermal atmospheric pressure plasma (NTP) in cancer research. Although increasing evidence suggests that NTP induces death of various cancer cell types, thus offering a promising alternative treatment, the mechanism of its therapeutic effect is little understood. In this study, we report for the first time that NTP led to apoptotic cell death in oral cavity squamous cell carcinoma (OSCC). Interestingly, NTP induced a sub-G1 arrest in p53 wild-type OSCCs, but not in p53-mutated OSCCs. In addition, NTP increased the expression levels of ATM, p53 (Ser 15, 20 and 46), p21, and cyclin D1. A comet assay, Western blotting and immunocytochemistry of γH2AX suggested that NTP-induced apoptosis and sub-G1 arrest were associated with DNA damage and the ATM/p53 signaling pathway in SCC25 cells. Moreover, ATM knockdown using siRNA attenuated the effect of NTP on cell death, sub-G1 arrest and related signals. Taken together, these results indicate that NTP induced apoptotic cell death in p53 wild-type OSCCs through a novel mechanism involving DNA damage and triggering of sub-G1 arrest via the ATM/p53 pathway. These findings show the therapeutic potential of NTP in OSCC.©2014 Elsevier Inc. All rights reserved.


Kim S.-Y.,Ajou University | Kim H.-J.,Ajou University | Kang S.U.,Ajou University | Kim Y.E.,Ajou University | And 5 more authors.
Oncotarget | Year: 2015

Recent research on non-thermal plasma (NTP, an ionized gas) has identified it as a novel cancer therapeutic tool. However, the molecular mechanism remains unclear. In this study, we demonstrated NTP induced cell death of head and neck cancer (HNC) through the AKT ubiquitin-proteasome system. NTP increased the gene expression of mitochondrial E3 ubiquitin protein ligase 1 (MUL1), an E3 ligase for AKT, and NTP-induced HNC cell death was prevented by MUL1 siRNA. We also showed that MUL1 inhibited the level of AKT and p-AKT and MUL1 expression was increased by NTP-induced ROS. Furthermore, we optimized and manufactured a new type of NTP, a liquid type of NTP (LTP). In syngeneic and xenograft in vivo tumor models, LTP inhibited tumor progression by increasing the MUL1 level and reducing p-AKT levels, indicating that LTP also has an anti-cancer effect through the same mechanism as that of NTP. Taken together, our results suggest that NTP and LTP have great potential for HNC therapy.


PubMed | Ajou University and PSM America Inc.
Type: Journal Article | Journal: Oncotarget | Year: 2015

Recent research on non-thermal plasma (NTP, an ionized gas) has identified it as a novel cancer therapeutic tool. However, the molecular mechanism remains unclear. In this study, we demonstrated NTP induced cell death of head and neck cancer (HNC) through the AKT ubiquitin-proteasome system. NTP increased the gene expression of mitochondrial E3 ubiquitin protein ligase 1 (MUL1), an E3 ligase for AKT, and NTP-induced HNC cell death was prevented by MUL1 siRNA. We also showed that MUL1 inhibited the level of AKT and p-AKT and MUL1 expression was increased by NTP-induced ROS. Furthermore, we optimized and manufactured a new type of NTP, a liquid type of NTP (LTP). In syngeneic and xenograft in vivo tumor models, LTP inhibited tumor progression by increasing the MUL1 level and reducing p-AKT levels, indicating that LTP also has an anti-cancer effect through the same mechanism as that of NTP. Taken together, our results suggest that NTP and LTP have great potential for HNC therapy.

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