ROS implication in a new antitumor strategy based on non-thermal plasma.

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.

Binding of 18-carbon unsaturated fatty acids to bovine ß-lactoglobulin--structural and thermodynamic studies.

Binding of 18-carbon unsaturated oleic and linoleic acid to lactoglobulin, the milk protein, has been studied for the first time by isothermal titration calorimetry (ITC) and X-ray crystallography. Crystal structures determined to resolution 2.10 Å have revealed presence of single fatty acid molecule bound in ß-barrel, the primary binding site, with carboxyl group hydrogen bonded to Glu62. The aliphatic chain of both ligands is in almost linear conformation and their interactions with the protein are similar to observed in structure of lactoglobulin with stearic acid. The ITC experiments showed that binding of unsaturated fatty acids to LGB is spontaneous and exothermic. The stoichiometry of binding is lower than 1.0, association constant is 9.7 × 10(5)M(-1) and 9.0 × 10(5)M(-1) for oleic and linoleic acid, respectively. Solvent relief seems to be the major contributor to entropic changes upon fatty acid binding to lactoglobulin.

Effects of a non thermal plasma treatment alone or in combination with gemcitabine in a MIA PaCa2-luc orthotopic pancreatic carcinoma model.

Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.