Publication Date

Fall 2022

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Advisor

Rachael French,

Subject Areas

Biology

Abstract

Cancer cells undergo metabolic reprogramming to meet the energy and metabolite demands of constant proliferation. Originally observed as the Warburg Effect, where cancer cells are more glycolytically active, recent research has shown that cancer cells can also utilize oxidative phosphorylation to meet these demands, better known as metabolic flux. Previous work from our lab showed that treatment with a Walnut Extract (WE) induced cell death in MDA-MB-231 and HeLa cells by destabilizing the mitochondrial outer membrane potential, suggesting that the extract may be able to impact oxidative phosphorylation. The aim of the current research was to further characterize the impact WE treatment had on both glycolytic and oxidative phosphorylation in cancer cells. Seahorse metabolic assays measuring the oxygen consumption and extracellular acidification of WE treated HeLa, MDA-MB-231, and MCF10a cells showed both a time- and dose-dependent reduction in oxidative and glycolytic rates in WE treated cells. The reduction in oxidative and glycolytic rates resulted in reduced total adenosine triphosphate (ATP) levels within treated cells when quantified. A permanent inhibition following washout of WE was also observed. The reduction in total ATP did not activate protein sensors of ATP and adenosine monophosphate (AMP) within the cell. The WE stimulated inhibition of oxidative and glycolytic activity that did not activate energy sensors within the cell suggests that WE treatment is inhibiting glycolysis and oxidative phosphorylation through an alternative mechanism.

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