Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase

Zeng, Xiaoyu; Liu, Lin; Zheng, Mengzhu; Sun, Huimin; Xiao, Junhui; Lü, Tao; Huang, Guangqian; Chen, Pianpian; Zhang, Jianmin; Feng, Zheng; Li, Hua; Duan, Qiuhong

doi:10.18632/oncotarget.7984

Cited by 64 publications

(53 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inhibiting H + /K + ‐ATPase by PPIs may contribute to a build‐up of protons inside the cells to decrease the intracellular pH, which reduces breast cancer cell growth . Alternatively, other studies indicated that in a proton pump–independent mechanism, PPIs can directly suppress cancer growth by targeting tumor‐specific T cell–originated protein kinase . As for tumor progression, the vital roles of hypoxic conditions and consequent acid pH of the tumor microenvironment are emphasized .…”

Section: Discussionmentioning

confidence: 99%

Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

Chen

Lee

Lin

et al. 2018

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Although current evidence suggests potential antitumor activity of proton pump inhibitors (PPIs), there is no population-based evidence of an association between PPI use and subsequent breast cancer risks. We used an observational case-control study to examine the association between prior PPI use and breast cancer occurrence. Additional analysis examined dose-response and age-stratified associations of PPIs with breast cancer. This study used data from the Taiwan National Health Insurance Research Dataset. A total of 64,234 women diagnosed with breast cancer between 2004 and in 2013 were selected as cases. Controls were 64,234 women without cancer who were selected by matching them with cases on the basis of sociodemographic characteristics and widely prevalent comorbidities. Each study subject's claims data were tracked back for 5 years to determine precancer prescriptions of PPIs. Logistic regression modeling was used for the analysis. A total of 11,871 (9.24%) women had used PPIs within the prior 5 years, 8.06% and 10.42% among cases and controls, respectively. Breast cancer patients were 25% less likely to have had prior PPI exposure after adjustment for comorbidities that predispose to PPI exposure (95%CI 0.72-0.78) in the risk of breast cancer occurrence. A dose-response effect was also detected, with the highest effect, 35% lower PPI odds (95%CI 0.61-0.70) among patients in the highest exposure category. Our findings may suggest that women at a higher-than-average risk of breast cancer may benefit from PPI prescriptions if they have medical conditions that could benefit from PPIs.

show abstract

Section: Discussionmentioning

confidence: 99%

Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

Chen

Lee

Lin

et al. 2018

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…The X-ray structure of the IDH1R132H heterodimer (PDB: 4UMX) [ 11 , 12 ] was chosen to generate a molecular model for our investigations. The non-commercial database, ZINC Drug Database (ZDD) containing over 2924 approved drugs and nutraceuticals were screened against this model in silicon by ICM-Pro 3.8.1 molecular docking software (Molsoft LLC, San Diego, CA) [ 13 ].…”

Section: Resultsmentioning

confidence: 99%

Structure based discovery of clomifene as a potent inhibitor of cancer-associated mutant IDH1

et al. 2017

Self Cite

View full text Add to dashboard Cite

Isocitrate dehydrogenase (IDH) plays an indispensable role in the tricarboxylic acid cycle, and IDH mutations are present in nearly 75% of glioma and 20% of acute myeloid leukemia. One IDH1R132H inhibitor (clomifene citrate) was found by virtual screening method, which can selectively suppress mutant enzyme activities in vitro and in vivo with a dose-dependent manner. The molecular docking indicated that clomifene occupied the allosteric site of the mutant IDH1. Enzymatic kinetics also demonstrated that clomifene inhibited mutant enzyme in a non-competitive manner. Moreover, knockdown of mutant IDH1 in HT1080 cells decreased the sensitivity to clomifene. In vivo studies indicated that clomifene significantly suppressed the tumor growth of HT1080-bearing CB-17/Icr-scid mice with oral administration of 100 mg/kg and 50 mg/kg per day. In short, our findings highlight clomifene may have clinical potential in tumor therapies as a safe and effective inhibitor of mutant IDH1.

show abstract

“…Interestingly, it is associated with a reduction in both baseline and interval development of hyperplastic polyps . In recent animal models, PPIs have been found to suppress the growth of colorectal cancer cells by inhibiting T‐cell‐originated protein kinase . Human studies are required to confirm these findings.…”

Section: Ppi and Gut Microbiotamentioning

confidence: 99%

Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome

2018

View full text Add to dashboard Cite

In recent years, proton pump inhibitors (PPIs) have been criticized for their various adverse interactions and side effects, creating a dilemma among practitioners regarding their use. Our goal is to review the proper use and possible side effects that might be caused by or associated with PPI use. Conclusions were drawn based on the evidence supporting or refuting short-term and long-term adverse events associated with PPI use. We also looked for the evidence regarding effects of PPIs on gut microbiota and their overall safety profile. Although there are significant discrepancies in the current literature regarding various adverse effects associated with PPI use, current data suggest that PPI use is not associated with an increased risk of bone fractures, community-acquired pneumonia, cardiovascular events, hypocalcemia, and gastric malignancies. A mild increased risk of vitamin B deficiency and chronic kidney disease, and a moderate increase in the risk of rebound hypersecretion, small intestinal bacterial overgrowth, and enteric infections, including Clostridium difficile, has been noted with PPI therapy. PPI's link with dementia and spontaneous bacterial peritonitis is not clear and requires further investigation. When used appropriately, PPIs are safe medications and are associated with minimal side effects. A clear indication and potential short-term and long-term side effects should be considered before starting PPI therapy.

show abstract

Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase

Cited by 64 publications

References 39 publications

Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

Structure based discovery of clomifene as a potent inhibitor of cancer-associated mutant IDH1

Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome

Contact Info

Product

Resources

About