Figure 2.

OA treatment quickly alters metabolism and restrains the PSP of cancer cells in vitro and in vivo

(A) Principal component analysis (PCA) score plot showing metabolic profiles of A549 cells treated with 200 μM OA and vehicle, respectively. The cells were treated for 8 h. (B) Heatmap showing differentially expressed metabolites between A549 cells treated with 200 μM OA or vehicle (DMSO diluted at a ratio of 1:1,000) for 8 h. The metabolites of the PSP are highlighted in red. The metabolites were subclassified as follows: (1) amino acids, (2) carbohydrates, (3) nucleotides, (4) organic acids, (5) lipids including fatty acids, and (6) unclassified. (C) A pathway-based analysis of metabolic alterations between A549 cells treated with 200 μM OA or vehicle for 8 h. The differential abundance score revealed the average change for metabolites in a pathway. Scores of 0.5 and −0.5 indicated increases or decreases in all detected metabolites in a pathway, respectively. (D) Scheme representing the metabolites and metabolic enzymes in the PSP. Metabolites significantly downregulated by OA treatment for 8 h are highlighted in deep sky blue, and metabolites with no significant alteration by OA treatment are highlighted in black. Metabolites participating in the pathway but not detected in the study are highlighted in white. Two enzymes, HGPRT and 5′-NT, responsible for the generation of metabolites perturbed by OA, are underlined in red. (E) Enzyme activities of HGPRT and 5′-NT in A549 cells treated with 200 μM OA or vehicle (DMSO diluted at a ratio of 1:1,000) for 8 h. (F) PCA score plot showing the impact of oral OA administration on metabolism of A549 tumor xenografts. (G) Three metabolites differentially expressed between A549 tumor xenografts with oral OA (n = 5) or vehicle (n = 5) administration. Error bars represent mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, Student’s t test.