Identification of autophagy inducers on cancer cell treated by plasma-activated lactate solution*

In recent years, there has been a need to establish cancer treatment method that is highly effective and have no side effects. One promising candidate, plasma-activated lactate solution (PAL), is produced by irradiating a Ringer’s lactate solution, one of the intravenous solution, with non-equilibrium atmospheric pressure plasma, which has the effect of selectively killing cancer cells. However, PAL has been found to induce autophagy, which aids in the survival of cancer cells. Therefore, it is important to inhibit autophagy to maintain the therapeutic effect even when PAL is diluted. PAL has been found to induce autophagy, which aids in the survival of cancer cells. This study aims to identify autophagy inducers, with the goal of inhibiting this process to enhance the effectiveness of PAL in cancer treatment.

 

PAL was produced by irradiating 10 ml of Ringer’s lactate solution with non-equilibrium atmospheric plasma under conditions of 15 kV_pp voltage, 60 Hz frequency, and a gas composition of 80% Ar + 10% O₂ + 10% N₂ for 5 minutes. The PAL components were analyzed using LC-MS and NMR, and the autophagy was evaluated through fluorescence analysis.

 

Interestingly, it was found that PAL induces autophagy through factors other than Reactive Oxygen and Nitrogen Species (RONS). Based on these findings, organic compounds within PAL and their autophagy-inducing potential were investigated. It was found for the first time that sodium acetate, pH-buffered glyoxylic acid, and pH-buffered 2,3-dimethyltartaric acid induce autophagy.