Plasma-activated Ringer's lactate (PAL) solution prepared by irradiating an intravenous solution with a non-equilibrium atmospheric pressure plasma is a potential new cancer therapy having no side effects. However, the induction of autophagy to avoid cell death has been confirmed to occur following exposure to PAL solution. It is thought that the antitumor effect of PAL solution could be weakened by this process, which is meant to maintain homeostasis in cells and assists tumorigenesis. Thus, it would be helpful to devise PAL-based cancer therapies that inhibit autophagy. Unfortunately, it is not yet clear which substances in PAL solution promote autophagy. The present work examined the mechanism by which PAL solution induces autophagy when treating MCF-7 human breast cancer cells. Autophagy was found to be temporarily induced upon exposure to PAL solution, suggesting that this effect contributes to cell proliferation. Although autophagy is associated with reactive oxygen and nitrogen species and/or acidic environments, in this study, significant autophagy was observed using a PAL solution diluted 1/256x without these stressors. Acetate, glyoxylate and 2,3-dimethyltartrate in the PAL solution were determined to promote autophagy. Interestingly, 2,3-dimethyltartrate was found to either induce cell death or autophagy depending on the concentration.
Keywords: 2,3-dimethyltartrate; Autophagy; breast cancer cells; non-equilibrium atmospheric pressure plasma; plasma-activated ringer’s lactate solution.
PAL solution was found to induce autophagy upon exposure to breast cancer cellsAutophagy was determined to be induced by reactive oxygen and nitrogen speciesSome organic acids generated by plasma induce autophagy without oxidative stressesSome organic acids generated by plasma induce autophagy without acidic stresses2,3-Dimethyltartrate induces cytotoxicity or autophagy depending on concentration.