Protein Pump Inhibitors Esomeprazole and Pantoprazole Increase the Chemosensitivity of CML cells against Imatinib

Abstract

Introduction: Proton pump inhibitors (PPIs) largely used drug to treat gastroesophageal disease such as gastric ulcers. Moreover, in recent years, several studies suggest that PPIs have important anti-cancer effect in monotherapy and or combination with chemotherapy. Objective: The aim of this study was to investigate whether esomeprazole and pantoprazole exhibit anti-cancer effect alone or could enhance chemosensitivity of CML cell line K562 to imatinib. Method: Human chronic myeloid leukemia (CML) cells were cultured and treated with different concentrations of esomeprazole, pantoprazole, and imatinib alone. Also these cells exposed to imatinib + esomeprazole and imatinib + pantoprazole combinations, respectively and incubated 24 h. The antiproliferative activities of the (PPIs) alone or in combination of imatinib was evaluated using the XTT colorimetric assay. Results: According to experimental data, neither PPIs showed any cytotoxic­ity on the K562 cell line at all concentrations except at 500 and 1000 µM. However, when combined with imatinib separately, they were found to have significant anti-cancer effects on K562 cells when compared to cell lines treated with imatinib alone (p<0.05). Conclusions: Taken together, the inhibition of V-ATPase via esomeprazole and pantoprazole might enhance the chemosensitivity of imatinib in CML cells. However, further studies are needed to be able to utilize PPIs in CML.