By Shreya Murali

Faculty Mentor: Dr. Randall Reif

Abstract

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. In healthy cells, proton pump proteins allow for H+ ions to permeate cellular membranes, regulating pH levels. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement, resulting in pH regulation limitations. As the cell increases in acidity, apoptosis is induced. In previous studies, omeprazole induced cell death in Jurkat T-Lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. In order to measure the extent of cell death, cytosolic esterase activity was measured by staining cells with Calcein-acetoxymethyl (AM) dye. Jurkat cells were exposed to PPIs omeprazole, dexlansoprazole, and esomeprazole for six-hours, and monitored for 30 hours to measure viability. Doxorubicin, a known chemotherapeutic, was also used as a positive control when testing viability. When imaged using fluorescence microscopy, if cells fluoresced, they were deemed viable, while nonfluorescent cells were deemed necrotic. At the 30-hour mark, dexlansoprazole had least viability (39.95 +/- 3.52%), followed by doxorubicin (62.86 +/- 1.80%), esomeprazole (66.24 +/- 1.59%), and omeprazole (69.29 +/- 2.01%), in comparison to the negative control (71.54 +/- 1.11%). The low viability of dexlansoprazole indicated the need for a toxicity study using the same PPIs and exposure methods, to determine the optimal drug concentration. The ideal drug concentration for dexlansoprazole was found to be 0.5 micromolar, while the other drugs had an ideal concentration of 1 micromolar. Future studies include the use of Annexin V-FITC and propidium iodide (PI) dye to determine the ability of the PPIs to induce apoptosis.