Non-thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT-116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.Plasma, considered as the fourth state of the matter, has already a broad range of applications in industry 1 and in medicine.2,3 Recently, the development of a new kind of plasma devices generating non-thermal plasma (NTP) has extended their potential applications especially in biology and medicine.4-6 NTP with a temperature less than 40 C at the point of treatment is a partially ionized media generated by excitation of a gas mixture in a discharge reactor. It contains electrons, positive/negative ions, radicals, various excited molecules, energetic photons (UV) and generates transient electric field. Given these interesting properties, potential applications are blood coagulation, 7 skin decontamination without significant skin damages, 8 wound healing, 9 and tumor treatment. 10The dose of NTP delivered is an important parameter to induce biological responses in tissue and cells.8 Indeed, low dose of plasma (<1 J cm À2) is able to induce inactivation of bacteria and proliferation of cells, 11,12 while higher dose (>7 J cm À2) can induce apoptosis of tumor cells including melanoma, breast cancer cells and hepatocellular carcinoma. [13][14][15][16][17] Sensenig et al. and Kim et al. have suggested that DNA damages and reactive species generated by plasma could be the main causes of this effect.14,18 In a recent work, Kalghatgi et al. showed that a low dose of NTP enhances endothelial cell proliferation due to the reactive oxygen species (ROS) generated by NTP mediated FGF-2 release.11 On non-tumorigenic breast epithelial cell line, NTP was also recently described to induce DNA damage leading to apoptosis due to the formation of intracellular ROS.19 ROS are potentially harmful on cellular metabolism by affec...

This work was conducted to evaluate the potential antitumor effect of an in vivo plasma treatment on a U87-luc glioma tumor. A pulsed DBD with ms pulses at moderate power was used for treatment. Electrical analyses and spectroscopic measurements were realized to characterize plasma properties. We showed that the plasma treatment was safe for mice. However, the reiterated long time plasma treatment (20 min, 3 consecutive days) produces a superficial burn. During plasma treatment, we observed an increase of subcutaneous temperature and a cutaneous skin pH reduction. After 5 d of plasma treatment, we observed a dramatical U87 bioluminescence decrease associated with a reduction of tumor volume in U87 glioma-bearing mice.