Date of Award

Spring 5-7-2021

Document Type

Honors Project

Degree Name

Bachelor of Science

Department

Chemistry

Department Chair or Program Director

Asper, Janet

First Advisor

Reif, Randall

Major or Concentration

Biochemistry

Abstract

Cancer cells are known to rely on the anaerobic energy pathway of glycolysis even under normoxic conditions, resulting in measurable intracellular acidification that may trigger cell death by apoptosis. In normal cells, the pH is restored by activation of voltage-gated proton pumps, preventing apoptosis. Proton pump inhibitors (PPIs), such as omeprazole, inhibit the action of these voltage-gated proton pumps. Research has shown that omeprazole is also capable of inducing caspase-dependent apoptosis in Jurkat T-lymphocytes, but this area of study remains largely unexplored. The goal of this research was to determine the temporal dynamics of caspase activity in Jurkat cells treated with omeprazole, dexlansoprazole, or esomeprazole. Caspase activation was observed with fluorescence microscopy and the fluorogenic caspase probe, L-bisaspartic acid rhodamine 110 (D2R). All three PPIs were shown to induce significant caspase activity when incubated in the presence of the drug over a 30-hour period, with dexlansoprazole showing comparative activity to the positive control, doxorubicin. Microfluidic devices were utilized to capture cells for real-time analysis, but only the doxorubicin showed caspase activity during these trials, with an onset time of 3.66 ± 1.67 hours. The microfluidic device experiments showed a decrease in cell-to-device binding affinity following the incubation period, indicating that PPI exposure alters the cell surface receptors in some capacity. Future studies will focus on addressing these challenges to allow for the elucidation of the intensity and timing of caspase activation, which will be beneficial for evaluating PPIs as potential cancer therapeutics.

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