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.

Keywords:

• Diffuse large B-cell lymphoma
• ouabain
• metabolomics

Acknowledgments

The authors thank Sijia Li and Runbin Sun for assistance and support in this study.

Disclosure statement

The authors declare that they have no potential conflicts of interest with respect to the research, authorship, and publication of this study.

Additional information

Funding

This work was supported by the National Natural Science Foundation of the People’s Republic of China under Grant (31171386 and 31371399).