Dasatinib and Trametinib Promote Anti-Tumor Metabolic Activity
Eric L. Bolf,
Thomas C. Beadnell,
Madison M. Rose,
Angelo D’Alessandro,
Travis Nemkov,
Kirk C. Hansen,
Rebecca E. Schweppe
Affiliations
Eric L. Bolf
Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Mail Stop 8106, Aurora, CO 80045, USA
Thomas C. Beadnell
Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Mail Stop 8106, Aurora, CO 80045, USA
Madison M. Rose
Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Mail Stop 8106, Aurora, CO 80045, USA
Angelo D’Alessandro
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Travis Nemkov
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Kirk C. Hansen
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Rebecca E. Schweppe
Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Mail Stop 8106, Aurora, CO 80045, USA
Thyroid cancer is the most common endocrine neoplasm, and despite its overall high survival rate, patients with metastatic disease or tumors that resist radioactive iodine experience a significantly worse prognosis. Helping these patients requires a better understanding of how therapeutics alter cellular function. Here, we describe the change in metabolite profiles after treating thyroid cancer cells with the kinase inhibitors dasatinib and trametinib. We reveal alterations to glycolysis, the TCA cycle, and amino acid levels. We also highlight how these drugs promote short-term accumulation of the tumor-suppressive metabolite 2-oxoglutarate, and demonstrate that it reduces the viability of thyroid cancer cells in vitro. These results show that kinase inhibition profoundly alters the metabolome of cancer cells and highlight the need to better understand how therapeutics reprogram metabolic processes, and ultimately, cancer cell behavior.
