ArticleJournal of the Chinese Medical Association : JCMA2022
Suppression of vacuolar-type ATPase and induction of endoplasmic reticulum stress by proton pump inhibitors.
Article in Journal of the Chinese Medical Association : JCMA, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 12 citations in OpenAlex.
- Exploring the Anticancer Potential of Proton Pump Inhibitors by Targeting GRP78 and V-ATPase: Molecular Docking, Molecular Dynamics, PCA, and MM-GBSA Calculations.International journal of molecular sciences · 2025Article
- Proton pump inhibitor attenuates acidic microenvironment to improve the therapeutic effects of MSLN-CAR-T cells on the brain metastasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Integrative pharmacovigilance and AI-based framework uncovers potential drug triggers in juvenile idiopathic arthritis.Frontiers in immunology · 2025Article
- Ubiquitin ligase subunit FBXO9 inhibits V-ATPase assembly and impedes lung cancer metastasis.Experimental hematology & oncology · 2024Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProton pump inhibitors (PPIs), such as esomeprazole, pantoprazole, dexlansoprazole, and rabeprazole, are one of the most commonly prescribed medications. Several studies have linked the long-term use of PPIs to a potentially increased risk of gastric cancer. Therefore, this study aimed to determine the underlying mechanism of PPI-mediated gastric cancer.
methodsLysosomes were isolated using immunoprecipitation. The inhibition of vacuolar-type ATPase (V-ATPase) by PPIs was assayed using a PiColorLock Gold Phosphate Detection System. PPI-induced lysosomal stress was analyzed using transcription factor EB (TFEB) nuclear translocation. PPI-induced endoplasmic reticulum (ER) stress was analyzed using the expression of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). Finally, reactive oxygen species (ROS) removal was determined using the activity of superoxide dismutase (SOD).
resultsPPIs caused a 70% inhibition of V-ATPase activity at 20 μM, leading to lysosomal stress through TFEB nuclear translocation; ER stress by inducing the expression of PERK, IRE1, and ATF6; and enhanced SOD activity for ROS removal.
conclusionThe long-term use of PPIs inhibits lysosomal V-ATPase, leading to ER stress and ROS accumulation, which may result in an increased risk of gastric cancer. Because lysosomes and the ER are common organelles in cells, physicians prescribing PPIs for gastroesophageal reflux and peptic ulcer diseases should pay more attention to the general effects of these agents on the human body.
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