Research Article
BibTex RIS Cite

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

Year 2018, Volume: 40 Issue: 4, 351 - 355, 29.12.2018
https://doi.org/10.7197/223.vi.499367

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, Volume: 40 Issue: 4, 351 - 355, 29.12.2018
https://doi.org/10.7197/223.vi.499367

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

Merve Ergül 0000-0003-4661-8087

Mustafa Ergül 0000-0003-4303-2996

Publication Date December 29, 2018
Acceptance Date December 25, 2018
Published in Issue Year 2018Volume: 40 Issue: 4

Cite

AMA Ergül M, Ergül M. Protein Pump Inhibitors Esomeprazole and Pantoprazole Increase the Chemosensitivity of CML cells against Imatinib. CMJ. December 2018;40(4):351-355. doi:10.7197/223.vi.499367