Cold atmospheric plasma (CAP) represents a promising therapy for selectively cancer killing. However, the mechanism of CAP-induced cancer cell death remains unclear. Here, we identified the tumor necrosis factor-family members, especially Fas, and overloaded intracellular nitric oxide participated in CAP induced apoptosis in A375 and A875 melanoma cell lines, which was known as extrinsic apoptosis pathway. This progress was mediated by antagonistic protein of reactive oxygen species, Sestrin2. The over expression of Sestrin2 induced by plasma treatment resulted in phosphorylation of p38 mitogen-activated protein kinase (MAPK), followed by increased expression of nitric oxide synthase (iNOS), Fas and Fas ligand. Depletion of Sestrin2 reduced iNOS and Fas expression, which was associated with reduction of plasma-induced apoptosis. In contrast, inhibition of iNOS activity and phosphorylation of p38 did not alter Sestrin2 expression in plasma-treated melanoma cells. Taken together, cold atmospheric plasma increases Sestrin2 expression and further activates downstream iNOS, Fas and p38 MAPK signaling to induce apoptosis of melanoma cell lines. These findings suggest a previously unrecognized mechanism in melanoma cells response to cold atmospheric plasma therapy.

Artificial enzymes as radical scavengers show great potentials in treatments of various diseases induced by oxidative stress. Herein, the quantitative analysis indicates that the intrinsic activity of nanocerias for the degradation of radicals is determined by the concentration of surface defects as well as their morphological features. The surface Ce fraction of the CeO nanozymes with a similar morphology can be used as a descriptor to index their catalytic activity as radical scavengers. Defect-abundant porous nanorods of ceria (PN-CeO) with a large surface area (141 m/g) and high surface Ce fraction (32.8%) deliver an excellent catalytic capability for the degradation of radicals, which is 15.5 times higher than that of Trolox. Results indicate that PN-CeO not only provides more surface catalytic centers but also supplies the active site with higher activity. Oxidative stress induced by doxorubicin (Dox), an essential medicine for a wide range of tumors, was used as the model system to evaluate the radical degradation ability of PN-CeO. Both in vitro cellar (H9c2 cells) and in vivo animal models revealed that PN-CeO did not affect the cell and rat growth and was able to alleviate the Dox-induced oxidative stress. Results suggest that the artificial PN-CeO nanozymes have potentials to function as an adjuvant medicine during tumor chemotherapy.

No abstract

Cold atmospheric-pressure plasma is a new technology, widely used in many fields of biomedicine, especially in cancer treatment. Cold plasma can selectively kill a variety of tumor cells, and its biological safety in clinical trials is also very important. In many cases, the patient's immune level is relatively low, so we first studied the safety assessment of plasma treatment in an immunocompromised animal model. In this study, we examined the safety of immuno-deficient nude mice by oral lavage treatment of plasma-activated water, and studied the growth status, main organs and blood biochemical indexes. Acute toxicity test results showed that the maximum dose of plasma treatment for 15 min had no lethal effect and other acute toxicity. There were no significant changes in body weight and survival status of mice after 2 min and 4 min of plasma-activated water (PAW) treatment for 2 weeks. After treatment, the major organs, including heart, liver, spleen, lung and kidney, were not significantly changed in organ coefficient and tissue structure. Blood biochemical markers showed that blood neutrophils and mononuclear cells were slightly increased, and the others remained unchanged. Liver function, renal function, electrolytes, glucose metabolism and lipid metabolism were not affected by different doses of PAW treatment. The above results indicate that PAW treatment can be used to treat immuno-deficient nude mice without significant safety problems.

Background Acute myeloid leukemia (AML) is a typically fatal malignancy and new drug and treatment need to be developed for a better survival outcome. Cold atmospheric plasma (CAP) is a novel technology, which has been widely applied in biomedicine, especially in various of cancer treatment. However, the changes in cell metabolism after CAP treatment of leukemia cells have been rarely studied. Methods In this study, we investigated the metabolite profiling of plasma treatment on leukemia cells based on Gas Chromatography Tandem Time-of-Flight Mass Spectrometry (GC-TOFMS). Simultaneously, we conducted a series of bioinformatics analysis of metabolites and metabolic pathways with significant differences after basic data analysis. Results 800 signals were detected by GC–TOF mass-spectrometry and then evaluated using PCA and OPLS-DA. All the differential metabolites were listed and the related metabolic pathways were analyzed by KEGG pathway. The results showed that alanine, aspartate and glutamate metabolism had a significant change after plasma treatment. Meanwhile, d -glutamine and d -glutamate metabolism were significantly changed by CAP. Glutaminase activity was decreased after plasma treatment, which might lead to glutamine accumulation and leukemia cells death. Conclusions We found the above two metabolic pathways vulnerable to plasma treatment, which might result in leukemia cells death and might be the cornerstone of further exploration of plasma treatment targets. Electronic supplementary material The online version of this article (10.1186/s12935-019-0856-4) contains supplementary material, which is available to authorized users.