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Anticancer Effects of Plasma and Its Underlying Mechanisms
- Author(s)
- NGUYEN, Ngoc Hoan
- Advisor
- Jong-Soo Lee
- Department
- 일반대학원 생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2016-08
- Language
- eng
- Keyword
- Life Sciences
- Alternative Abstract
- The therapeutic potential of nonthermal atmospheric-pressure plasma for cancer treatment via generation of reactive species and sequential induction of decreased mitochondrial membrane potential and apoptosis, has been reported recently. Current studies have unveiled extensive genetic diversity both between and within tumour, called inter- and intra-tumour heterogeneity, which poses a challenge to personalized cancer medicine. Therefore, the heterogeneity of cancer cells need to be addressed to design effective anticancer treatments. In this study, I show that treatment with nonthermal atmospheric-pressure plasma dissolved in a liquid (liquid plasma) induces oxidative stress in heterogeneous populations of cancer cells and ultimately kills these cells via apoptosis, regardless of genetic status, e.g., mutations in p53 and other DNA-damage-response genes. I found that liquid plasma markedly increased the concentration of intracellular and mitochondrial reactive oxygen species (ROS), reflecting an influx from the extracellular milieu. Liquid plasma contributed to mitochondrial accumulation of ROS and depolarization of mitochondrial membrane potential with consequent cell death. Healthy normal cells, however, were little affected by the liquid-plasma treatment. The antioxidant N-acetylcysteine blocked liquid-plasma-induced cell death. A knockdown of CuZn-superoxide dismutase or Mn-SOD enhanced the plasma-induced cell death, whereas expression of exogenous CuZn-SOD, Mn-SOD, or catalase blocked the cell death. These results suggest that the mitochondrial dysfunction mediated by ROS production is a key contributor to liquid-plasma-induced apoptotic cell death, regardless of genetic variation. In addition, for the first time, in this study, I introduce nonthermal atmospheric-pressure plasma that is dissolved in a liquid to address the problem of limited penetration of direct plasma treatment, which is an obstacle to effective delivery to tumors that locate at internal tissues. Furthermore, there is another advantage of liquid plasma that can be stored for up to 6 months without losing its anticancer cytotoxicity. Together, through this study, I suggest that liquid plasma may have clinical applications, e.g., the development of therapeutic strategies and prevention of disease progression despite tumor heterogeneity.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Bioscience > 4. Theses(Ph.D)
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