Fatty acid synthesis is crucial in supporting the survival and proliferation of multiple forms of cancer. The high metabolic demands of fatty acid synthesis are regulated by the AMP-activated kinase and activity of the fatty acid synthase enzyme. In this study, the roles of these enzymes in diffuse large B-cell lymphoma (DLBCL) were investigated by genetic knock-down and pharmacological activation of AMP-activated kinase by metformin, and selective inhibition of fatty acid synthase using the novel drug Fasnall. We observed distinct heterogeneity and adaptive plasticity of lipid metabolism in a panel of DLBCL cell lines and demonstrate the therapeutic potential of inhibiting fatty acid synthesis in a subset of DLBCL cells. The translational relevance of these in vitro data is supported by the strong correlation between AMP-activated protein kinase expression in primary DLBCL samples and disease relapse. Inhibition of fatty acid synthase with Fasnall may represent a therapeutic option for DLBCL that preferentially subverts to de novo fatty acid synthesis.
- Adenosine Monophosphate Apoptosis Cell Line, Tumor Cell Survival Fatty Acid Synthases/genetics Humans *Lymphoma, Large B-Cell, Diffuse/drug therapy/genetics *Pharmaceutical Preparations Protein Kinases *Lymphoma and Non-Hodgkin disease *cell cycle and apoptosis changes *metabolism *pharmacotherapeutics
- cell cycle and apoptosis changes
- Lymphoma and Non-Hodgkin disease