Energy and material metabolism is the basic guarantee for cell survival. Adenosine triphosphate (ATP) is a currency in the cell that is used to store and deliver energy. In normal tissues, 90% of the ATP comes from oxidative phosphorylation, whereas only 10% comes from glycolysis [
33]. In aerobic conditions, glycolysis is inhibited, known as the Pasteur effect. However, Warburg found that tumor cells are still prevalent with high rates of glucose uptake even under oxygenated conditions. The increased glycolytic metabolism and increased metabolites of lactate, which are ubiquitous in various tumor cells, called as the Warburg effect [
34,
35]. Although the efficiency of glycolysis is low, tumor cells can benefit from glycolysis: Firstly, Due to the rapid growth of tumor cells, there is a great demand for energy and more glycolytic production of ATP is required. Secondary, glycolysis intermediates such as 6-phosphate glucose, pyruvate can synthesize fatty acids, nucleic acids which are important for cell metabolism and biosynthesis. Therefore, the energy and material metabolism of tumor cells and normal cells are quite different. Atmospheric cold plasma, as a newly developed technology, can selectively induce tumor cell death. In addition, some related apoptosis pathway factors were reported although more mechanism need to be investigated. In our study, instead of study on the single apoptotic protein, we investigated the whole metabolism profiling to understand the effect of plasma on the metabolism of tumor cells. Because the metabolomic data typically contains a large number of variables that are interrelated, multivariate statistical methods such as PCA and OPLS-DA were used in this study [
36]. We demonstrated the large scale metabolic profiling using GC-TOF mass spectrometry and found numerous significant differences between the gas control group and the plasma treatment group in myeloma tumor cells. By KEGG analysis of the metabolic pathways we found that beta-alanine metabolism pathway was the most significant changes after He gas plasma treatment in myeloma LP-1 cells. Alanine, beta-alanine and sarcosine share the same chemical formula C
3H
7NO
2, but are structurally different. By GC–TOFMS analysis, beta-alanine is easy to separate from alanine and sarcosine duo to its distinct mass spectrum [
37]. Beta-alanine is a direct precursor of pantothenic acid (PA) which is needed for the synthesis of coenzyme A (CoA). In the tricarboxylic acid (TCA) cycle, CoA is important for pyruvate to enter as acetyl-CoA, and for α-ketoglutarate to be transformed to succinyl-CoA [
38]. In addition, CoA is involved in the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine [
39]. Therefore, by He plasma treatment, beta-alanine metabolism in myeloma tumor cells was suppressed, which disturbing the energy and material metabolism of the tumor cells and results in tumor cells death. Our data illustrated some details about the dysregulation of metabolism profiling by gas plasma for the first time. Although more researches need to be done to further analyze the mechanism under molecular microstructure, this study gives a general direction for further study. Meanwhile, more tumor cell lines and the treatment by different types of gas plasma devices will be done for metabolite profiling analysis, to further illustrate the biological effects in various tumor cells by different reactive species in gas plasma.