Pantoprazole is a member of the benzimidazole class, acts as a proton pump inhibitor, as a potent inhibitor of gastric acid secretion and is widely used for the treatment of gastroesophageal reflux, dyspepsia and peptic ulcer.
Take only under medical supervision
It also exerts an anti-inflammatory action (1) in gastric and endothelial parietal cells and an antioxidant action through the direct scavenging of reactive oxygen species (2) and has been identified as an oncokinase inhibitor (3).
Pantoprazole offers a lower risk of drug interaction due to lower liver metabolism (4)and this property is useful when used as a potential anticancer therapeutic agent (5). It also did not affect cyclosporin A serum levels in patients who received renal transplantation (6).
This study investigated the effects and mechanism of pantoprazole that led to cell cycle arrest by inducing apoptosis on leukemic cell lines with multi-drug resistance (7).
As a medication, pantoprazole is also inserted in the form of Sodium Pantoprazole or Sodium Pantoprazole Sesquihydrate.
Like all drugs it can cause side effects. Always ask the physician.
Pantoprazole studies
Molecular Formula: C16H15F2N3O4S
Molecular Weight: 383.4 g/mol
CAS: 102625-70-7 142678-35-1
EC Number: 600-331-6
Synonyms:
- Protonix
- Pantoloc
- Pantozol
- Pantoprozole
- Pantoprazolum
- Astropan
- Somac Control
- Panyocid
- Pantecta Control
- Zosecta
- Pharmakon1600-01505818
- Pantor
- AC-679
- L-Pantoprazole
- Pantoprazol
- Tox21_111477
- 5-(Difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridyl)methyl)sulfinyl)benzimidazole
- 1H-Benzimidazole, 5-(difluoromethoxy)-2-(((3,4-dimethoxy-
- 2-pyridinyl)methyl)sulfinyl)-
- 5-(difluoromethoxy)-2-{[(3,4-dimethoxypyridin-2-yl)methyl]sulfinyl}-1H-
- benzimidazole
- 6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-
- benzimidazole
- 6-(difluoromethoxy)-2-[(3,4-dimethoxy-2-pyridyl)methylsulfinyl]-1H-benzimidazole
- 1H-Benzimidazole, 6-(difluoromethoxy)-2-((S)-((3,4-dimethoxy-
- 2-pyridinyl)methyl)sulfinyl)-
- 2-(((3,4-Dimethoxy-2-pyridinyl)methyl)-sulfinyl)-5-methyl-1H-1,3-benzimidazole
- 5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methanesulfinyl]-3H-1,3-
- benzodiazole
- 5-(difluoromethoxy)-2-(((3,4-dimethoxypyridin-2-yl)methyl)sulfinyl)-1H-
- benzo[d]imidazole
- 5-Difluoromethoxy-2-(3,4-dimethoxy-pyridin-2-ylmethanesulfinyl)-1H-
- benzoimidazole
- 5-(difluoromethoxy)-2-[(3,4-dimethoxy-2-pyridyl)methylsulfinyl]-1H-benzimidazole
- 5-(difluoromethoxy)-2-((3,4-dimethoxypyridin-2-yl)methylsulfinyl)-1H-
- benzo[d]imidazole
References_________________________________________________
(1) Zeng X, Liu L, Zheng M, Sun H, Xiao J, Lu T, Huang G, Chen P, Zhang J, Zhu F, Li H, Duan Q. Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2016 Apr 19;7(16):22460-73. doi: 10.18632/oncotarget.7984. PMID: 26967058; PMCID: PMC5008373.
Abstract. T-cell-originated protein kinase (TOPK) is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug treatment of tumor. Pantoprazole (PPZ) was identified to be a TOPK inhibitor from FDA-approved drug database by structure based virtual ligand screening. Herein, the data indicated that pantoprazole inhibited TOPK activities by directly binding with TOPK in vitro and in vivo. Ex vivo studies showed that pantoprazole inhibited TOPK activities in JB6 Cl41 cells and HCT 116 colorectal cancer cells. Moreover, knockdown of TOPK in HCT 116 cells decreased their sensitivities to pantoprazole. Results of an in vivo study demonstrated that i.p. injection of pantoprazole in HCT 116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after pantoprazole treatment. In short, pantoprazole can suppress growth of colorectal cancer cells as a TOPK inhibitor both in vitro and in vivo.
(2) Udelnow A, Kreyes A, Ellinger S, Landfester K, Walther P, Klapperstueck T, Wohlrab J, Henne-Bruns D, Knippschild U, Würl P. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One. 2011;6(5):e20143. doi: 10.1371/journal.pone.0020143.
Abstract. Background Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines.. Methodology/Principal Findings. Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa-2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non-toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omeprazole led to accumulation of phagophores and early autophagosomes in ASPC-1 and MiaPaCa-2 cells. Signal changes indicating inhibited proliferation and programmed cell death were found by proton NMR spectroscopy of both cell lines when treated with omeprazole which was identified intracellularly. Omeprazole modulates the lysosomal transport pathway as shown by Western blot analysis of the expression of LAMP-1, Cathepsin-D and β-COP in lysosome- and Golgi complex containing cell fractions. Acridine orange staining revealed that the pump function of the vATPase was not specifically inhibited by omeprazole. Gene expression of the autophagy-related LC3 gene as well as of Bad, Mdr-1, Atg12 and the vATPase was analysed after treatment of cells with 5-fluorouracil and omeprazole and confirmed the above mentioned results. Conclusions. We hypothesise that omeprazole interacts with the regulatory functions of the vATPase without inhibiting its pump function. A modulation of the lysosomal transport pathway and autophagy is caused in pancreatic cancer cells leading to programmed cell death. This may circumvent common resistance mechanisms of pancreatic cancer. Since omeprazole use has already been established in clinical practice these results could lead to new clinical applications.
(3) Zeng X, Liu L, Zheng M, Sun H, Xiao J, Lu T, Huang G, Chen P, Zhang J, Zhu F, Li H, Duan Q. Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2016 Apr 19;7(16):22460-73. doi: 10.18632/oncotarget.7984. PMID: 26967058; PMCID: PMC5008373.
(4) Shin, J. M., & Kim, N. (2013). Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. Journal of neurogastroenterology and motility, 19(1), 25.
Abstract. Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H+, K+-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. Several factors must be considered in understanding the pharmacodynamics of PPIs, including: accumulation of PPI in the parietal cell, the proportion of the pump enzyme located at the canaliculus, de novo synthesis of new pump enzyme, metabolism of PPI, amounts of covalent binding of PPI in the parietal cell, and the stability of PPI binding. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. Though CYP2C19 and CYP3A4 polymorphism are major components of PPI metabolism, the pharmacokinetics and pharmacodynamics of racemic mixture of PPIs depend on the CYP2C19 genotype status. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life.
(5) Zhang, B., Ling, T., Zhaxi, P., Cao, Y., Qian, L., Zhao, D., ... & Zou, X. (2019). Proton pump inhibitor pantoprazole inhibits gastric cancer metastasis via suppression of telomerase reverse transcriptase gene expression. Cancer Letters, 452, 23-30.
Abstract. The effect of proton pump inhibitors (PPIs) on cancer risk has received much attention recently. Over the last two decades, we and others have disclosed that PPIs exerted anticancer effects. Telomerase reverse transcriptase (TERT) is essential for telomere maintenance. The activation of TERT is considered a crucial step in tumorigenesis; therefore, it is a potential therapeutic target against cancer. However, whether PPIs suppress gastric cancer by targeting TERT remains elusive. Our study demonstrated that PPZ treatment repressed TERT expression in gastric cancer cells via regulating TERT promoter activity by disturbing the interaction of STAT3 with the TERT gene. Additionally, PPZ led to chromatin remodeling within the TERT gene and resulted in a more compacted spatial conformation that is known to be associated with gene silencing. PPZ downregulated the TERT gene to inactivate the Wnt/β-catenin signaling pathway and reverse the EMT process, finally inhibiting gastric cancer metastasis both in vitro and in vivo. Our results suggest that PPIs may be potentially developed as effective as well as relatively safe and specific anticancer agents.
(6) Lorf, T., Ramadori, G., Ringe, B., & Schwörer, H. (2000). Pantoprazole does not affect cyclosporin A blood concentration in kidney-transplant patients. European journal of clinical pharmacology, 55, 733-735.
Abstract. Objective: Renal-transplant patients who are immunosuppressed with cyclosporin A (CyA) are often treated with proton-pump inhibitors to prevent ulcer disease. No data are available on the effect of the novel proton-pump inhibitor pantoprazole on CyA levels. Methods: In a controlled treatment, we investigated the effect of pantoprazole, which was administered in a pragmatic schedule for acid suppression (40 mg as single oral dose at 2200 hours) in six renal-transplant patients who received CyA (Sandimmun optoral, 50–175 mg twice daily) and prednisolone (5–7.5 mg/24 h). CyA trough levels (0730–0800 hours) were measured by immunoassay. Results: In the absence of pantoprazole, mean CyA trough levels measured on three consecutive days were between 164 ng/ml and 173 ng/ml (therapeutic range 120–200 ng/ml). Pantoprazole did not affect CyA trough levels during an observation period up to 3 months long.
(7) Liu M, Tang R, Jiang Y. Pantoprazole Induces Apoptosis of Leukemic Cells by Inhibiting Expression of P-Glycoprotein/Multidrug Resistance-Associated Protein-1 Through PI3K/AKT/mTOR Signaling. Indian J Hematol Blood Transfus. 2017 Dec;33(4):500-508. doi: 10.1007/s12288-017-0808-x. Epub 2017 Mar 30. PMID: 29075060; PMCID: PMC5640553.
Abstract. This study aims to investigate the effects and mechanism of pantoprazole on multidrug resistant leukemia K562/A02 and K562/ADM cell lines. K562/A02 and K562/ADM cells at logarithmic growth phase were pre-treated with different concentration of pantoprazole (0, 50, 100, 200 μg/mL) for 24 h. Flow cytometry was used to measure the cell growth cycle and apoptosis. RT-PCR and Western blot were used to measure the expression of p-PI3K, p-AKT, p-mTOR, P-glycoprotein (P-gp) and multidrug resistance-associated protein-1 (MRP1). Pantoprazole pretreatment significantly increased the ratio of G0/G1 phase but decreased the S phase of K562/A02 and K562/ADM cells in dose-dependent manner (p < 0.05). Flow cytometry analysis indicated that pretreatment of leukemic cells with pantoprazole induced apoptosis in a dose-dependent manner. RT-PCR and Western blot analysis indicated that pantoprazole pretreatment inhibited the mRNA and protein expression of p-PI3K, p-Akt, p-mTOR, P-gp and MRP1 in K562/A02 and K562/ADM cells in a dose-dependent manner (p < 0.05). Pantoprazole arrested cell cycle and induced apoptosis of multidrug resistant leukemic cells by inhibiting the expression of P-gp and MRP1 through PI3K/Akt/mTOR signaling pathway.
1H-benzimidazole 
