Temporal Dynamics of Caspase Activation in PPI-treated Cancer Cells

by Ashley Utz

Faculty Mentor: Professor Randall Reif

Cancer cells rely on glycolysis even under normoxic conditions. The use of this pathway results in measurable intracellular acidification, which is characterized as an early event in the apoptosis program. The pH is restored by activation of voltage- gated proton pumps, preventing acidification. Proton pump inhibitors (PPIs), such as omeprazole, inhibit the H+/K+-ATPase system found at the secretory surface of gastric parietal cells. Research has shown that omeprazole is also capable of inducing caspase-dependent apoptosis in Jurkat T-lymphocytes. However, the effects of PPIs on caspase activity remain largely unknown. The goal of this study was to determine the temporal dynamics of caspase activity in Jurkat cells treated with omeprazole, dexlansoprazole, or esomeprazole for six hours. After the incubation period, cells were held in place by anti- CD71 antibodies on the device’s affinity surface and fluorescence microcopy was used to monitor caspase activity in real time. Caspase activation was observed over a six-hour period with the fluorogenic caspase probe, L-bisaspartic acid rhodamine 110 (D2R). Elucidation of the intensity and timing of caspase activation will be beneficial for evaluating PPIs as potential cancer therapeutics.

One Reply to “Temporal Dynamics of Caspase Activation in PPI-treated Cancer Cells”

  1. Ashley – thank you for sharing this poster to a wider audience. I enjoyed your presentation earlier this week on this topic.

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