Date on Master's Thesis/Doctoral Dissertation
Biochemistry and Molecular Biology
Committee Co-Chair (if applicable)
Glutamine--Metabolism; Cancer cells--Growth
In tumor cells, glutamine metabolism provides anaplerotic carbon for the TCA cycle, fatty acid synthesis, and precursors for the production of nucleotides and glutathione. This metabolic alteration is primarily driven by disruptions in oncogenic or tumor suppressor function and results in glutamine dependency for tumor cell survival. Troglitazone, a PPARγ agonist, has been reported to alter glutamine metabolism. This thesis project addresses whether troglitazone treatment could disrupt glutamine metabolism in glutamine-dependent tumor cells. Results obtained with troglitazone treatment include: dose-dependent inhibition of cell proliferation, glutamine uptake, glutaminolytic protein expression, steady-state ATP levels, and glutamine carbon flux into the TCA cycle. Silencing PPAR/ activity by using siRNA or a PPARγ antagonist did not alter troglitazone’s effects on cell proliferation or glutamine uptake. Furthermore, troglitazone treatment caused the suppression of c-Myc protein expression, an oncogene known to regulate glutaminolysis. Thus, troglitazone was shown to disrupt tumor glutamine metabolism through a PPAR-independent manner.
Reynolds, Miriam R. 1965-, "Troglitazone suppresses glutamine metabolism and tumor cell growth through a ppar-independent mechanism." (2014). Electronic Theses and Dissertations. Paper 1770.