Metabolomic approach to characterize the metabolic phenotypes and varied response to ouabain of diffuse large B-cell lymphoma cells

Abstract

Germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtype diffuse large B-cell lymphoma (DLBCL) showed differential prognosis. Our results suggested that ouabain induced stronger inhibition of growth in Su-DHL4 (GCB), and it triggered obvious apoptosis in Su-DHL4 rather than in OCI-Ly3 (ABC). Two subtype cell lines also showed distinct metabolic phenotypes involving remarkable enrichment of Ribulose-5-Phosphate, hypoxanthine, and guanine in Su-DHL4 cells. Ouabain disturbed metabolic patterns of both cell lines dose-dependently manifested inhibition of free fatty acids and amino acids metabolism, among which ornithine was further identified as potential quantitative marker. Up-regulated Ribulose-5-Phosphate and NADPH/NADP+ level, SOD1, and CAT expression by ouabain enabled OCI-Ly3 cells to resist ROS, while enhanced hypoxanthine and guanine oxidation promoting ROS generation by ouabain, and lowered capacity of scavenging ROS indicated by lowered SOD1 and CAT expression and NADPH/NADP+ levels in Su-DHL4 cells made it more vulnerable to apoptosis through caspase 7 pathway.