Research Article
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.
References
- 1. Ergül M, Ergül M, Tutar Y. Important Anti-Cancer Applications of Protein Based Nanoparticles. Current Proteomics 2013;10:334-340.
- 2. Inoue A, Kobayashi CI, Shinohara H, et al. Chronic myeloid leukemia stem cells and molecular target therapies for overcoming resistance and disease persistence. Int J Hematol 2018;108(4):365-370.
- 3. Dalgıç CT, Kaymaz BT, Özkan MC, et al. Investigating the Role of JAK/STAT Pathway on Dasatinib-Induced Apoptosis for CML Cell Model K562. Clin Lymphoma Myeloma Leuk 2015;15.
- 4. Li X, Pang J, Xue W, et al. Inducible SHP-2 activation confers resistance to imatinib in drug-tolerant chronic myeloid leukemia cells. Toxicol Appl Pharmacol 2018;360:249-256.
- 5. Udelnow A, Kreyes A, Ellinger S, et al. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One 2011;6(5):e20143.
- 6. Lu ZN, Tian B, Guo XL. Repositioning of proton pump inhibitors in cancer therapy. Cancer Chemother Pharmacol 2017;80(5):925-937.
- 7. Wang X, Liu C, Wang J, et al. Proton pump inhibitors increase the chemosensitivity of patients with advanced colorectal cancer. Oncotarget 2017;8(35):58801-58808.
- 8. Lindner K, Borchardt C, Schöpp M, et al. Proton pump inhibitors (PPIs) impact on tumour cell survival, metastatic potential and chemotherapy resistance, and affect expression of resistance-relevant miRNAs in esophageal cancer. J ExpClin Cancer Res 2014;33:73.
- 9. Marino ML, Fais S, Djavaheri-Mergny M, et al. Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells. Cell Death Dis 2010;1:e87.
- 10. Song T, Jeon HK, Hong JE, et al. Proton Pump Inhibition Enhances the Cytotoxicity of Paclitaxel in Cervical Cancer. Cancer Res Treat 2017;49(3):595-606.
- 11. Hou Y, Hu Q, Huang J, Xiong H. Omeprazole Inhibits Cell Proliferation and Induces G0/G1 Cell Cycle Arrest through Up-regulating miR-203a-3p Expression in Barrett's Esophagus Cells. Front Pharmacol 2018;8:968.
- 12. Patlolla JM, Zhang Y, Li Q, et al. Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats. Int J Oncol 2012;40(1):170-5.
Year 2018,
, 351 - 355, 29.12.2018
Abstract
References
- 1. Ergül M, Ergül M, Tutar Y. Important Anti-Cancer Applications of Protein Based Nanoparticles. Current Proteomics 2013;10:334-340.
- 2. Inoue A, Kobayashi CI, Shinohara H, et al. Chronic myeloid leukemia stem cells and molecular target therapies for overcoming resistance and disease persistence. Int J Hematol 2018;108(4):365-370.
- 3. Dalgıç CT, Kaymaz BT, Özkan MC, et al. Investigating the Role of JAK/STAT Pathway on Dasatinib-Induced Apoptosis for CML Cell Model K562. Clin Lymphoma Myeloma Leuk 2015;15.
- 4. Li X, Pang J, Xue W, et al. Inducible SHP-2 activation confers resistance to imatinib in drug-tolerant chronic myeloid leukemia cells. Toxicol Appl Pharmacol 2018;360:249-256.
- 5. Udelnow A, Kreyes A, Ellinger S, et al. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One 2011;6(5):e20143.
- 6. Lu ZN, Tian B, Guo XL. Repositioning of proton pump inhibitors in cancer therapy. Cancer Chemother Pharmacol 2017;80(5):925-937.
- 7. Wang X, Liu C, Wang J, et al. Proton pump inhibitors increase the chemosensitivity of patients with advanced colorectal cancer. Oncotarget 2017;8(35):58801-58808.
- 8. Lindner K, Borchardt C, Schöpp M, et al. Proton pump inhibitors (PPIs) impact on tumour cell survival, metastatic potential and chemotherapy resistance, and affect expression of resistance-relevant miRNAs in esophageal cancer. J ExpClin Cancer Res 2014;33:73.
- 9. Marino ML, Fais S, Djavaheri-Mergny M, et al. Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells. Cell Death Dis 2010;1:e87.
- 10. Song T, Jeon HK, Hong JE, et al. Proton Pump Inhibition Enhances the Cytotoxicity of Paclitaxel in Cervical Cancer. Cancer Res Treat 2017;49(3):595-606.
- 11. Hou Y, Hu Q, Huang J, Xiong H. Omeprazole Inhibits Cell Proliferation and Induces G0/G1 Cell Cycle Arrest through Up-regulating miR-203a-3p Expression in Barrett's Esophagus Cells. Front Pharmacol 2018;8:968.
- 12. Patlolla JM, Zhang Y, Li Q, et al. Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats. Int J Oncol 2012;40(1):170-5.
There are 12 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Basic Science Research Articles |
| Authors | |
| Publication Date | December 29, 2018 |
| Acceptance Date | December 25, 2018 |
| Published in Issue | Year 2018 |