Sensitization of Pancreatic Cancer Cells to Radiation by Cerium Oxide Nanoparticle-Induced ROS Production
Menée sur des cellules humaines de cancer du pancréas et à l'aide d'un modèle murin, cette étude identifie un mécanisme par lequel des nanoparticules d'oxyde de cérium, en augmentant la formation de dérivés réactifs de l'oxygène, sensibilisent les cellules tumorales aux rayonnements ionisants
Side effect of radiation therapy (RT) remains the most challenging issue for pancreatic cancer treatment. In this report we determined whether and how cerium oxide nanoparticles (CONPs) sensitize pancreatic cancer cells to RT. CONP pretreatment enhanced radiation-induced reactive oxygen species (ROS) production preferentially in acidic cell-free solutions as well as acidic human pancreatic cancer cells. In acidic environments,CONPs favor the scavenging of superoxide radical over the hydroxyl peroxide resulting in accumulation of the latter whereas in neutral pH CONPs scavenge both. CONP treatment prior to RT markedly potentiated the cancer cell apoptosis both in culture and in tumors and the inhibition of the pancreatic tumor growth without harming the normal tissues or host mice. Taken together, these results identify CONPs as a potentially novel RT-sensitizer as well as protectant for improving pancreatic cancer treatment. Cerium oxide nanoparticles (CONPs) sensitize acidic cancer cells and desensitize neutral normal cells to radiation therapy (RT)-induced hydrogen peroxide accumulation and subsequent cell death in a cell acidity dependent manner. In the absence of CONPs, cancer cells are relatively resistant to RT-induced superoxide accumulation compared to normal cells (compare 2 to 1). In the absence of RT, the acidic cancer cellular environment promotes the superoxide scavenging activity of Ce3+ state of CONPs but blocks the hydrogen peroxide scavenging activity of Ce4+ state of CONPs resulting in the accumulation of hydrogen peroxide, which does not happen to the neutral environment of normal cells (compared 4 to 3). In the presence of CONPs, RT induces even more hydrogen peroxide accumulation in cancer cells presumably by aiding in the switch of the oxidation states of CONPs from Ce4+ to Ce3+ (compare 6 to 4), which does not occur to the neutral environment of normal cells (compared 6 to 5).
http://linkinghub.elsevier.com/retrieve/pii/S1549963412006077?showall=true