Effect of cold atmospheric plasma treatment on the metabolites of human leukemia cells

Abstract

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.

Cold Atmospheric Plasma: A Powerful Tool for Modern Medicine

“…This results in intermediate metabolites that tumorous cells can use for growth and proliferation [116][117][118]. Xu et al [119] studied CAP effects on altered cancer cell metabolic activity. Their KEGG and GC-TOFMS analyses highlighted that leukaemia cells had different alanine, aspartate, and glutamate metabolism.…”

“…This decreases the conversion of glutamine to glutamic acid. Deficiency of Glutamic acid, simultaneously with glutamine accumulation can lead to suppression of proliferation and even cell death in leukemia cells [119].…”

Dosing: The key to precision plasma oncology

“…Various signaling effects were altered on CAP‐induced apoptosis in different studies. We have previously shown that CAP can selectively induce the apoptosis of triple‐negative breast cancer cells both in vitro and in vivo by suppressing the phosphorylation level of JNK [ 17 ] and proposed the use of “cell number,” “treatment time,” “area,” and “depth” as key parameters controlling CAP dose through the establishment of a linear model from an orthogonal experimental design. [ 16 ] CAP was lately shown to induce apoptosis in melanoma cells via sestrin2‐mediated nitric oxide synthase signaling [ 33 ] and by targeting the HGF/c‐MET downstream pathway.…”

“…The selectivity of CAP on cancer cells has been reported in various types of cancer cells such as triple‐negative breast cancer, [ 17 ] melanoma, [ 33,34 ] non‐small‐cell lung cancer, [ 42 ] head and neck carcinoma, [ 15 ] and pancreatic cancer [ 13 ] (Table 1). It was stated that malignant cells have higher baseline ROS levels than normal cells due to elevated ROS creation and inefficient redox scavenging.…”

“…Previous studies revealed the variation of the plasma selectivity for different breast cancer subtypes subjected to appropriate dosing control. [ 16,17 ] These encouraging results collectively suggest the dose‐dependent efficacies of CAP regarding its medical applications and underlie the importance of dosing in translating the plasma treatments into precision medicine.…”