ArticleScientific reports2018
Indomethacin Disrupts Autophagic Flux by Inducing Lysosomal Dysfunction in Gastric Cancer Cells and Increases Their Sensitivity to Cytotoxic Drugs.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- New Functions of Mitochondrial Dysfunction in Gastric Cancer: From Molecular Processes to Potential Treatments.International journal of molecular sciences · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- p62/SQSTM1-TRAF6/RIP1 complexes activate NF-κB-mediated PD-L1 expression and promote T-cell apoptosis in MKN45 gastric cancer cells.Journal of gastrointestinal oncology · 2026Article
- A comparative study of some NSAIDs with natural products: integrating in vitro anticancer efficacy, in vivo antiulcerative effect, histochemistry, and in silico analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- NSAID targets SIRT3 to trigger mitochondrial dysfunction and gastric cancer cell death.iScience · 2024Article
- Oxidative stress in the tumor microenvironment in gastric cancer and its potential role in immunotherapy.FEBS open bio · 2023Review
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Targeting mitochondria as a therapeutic anti-gastric cancer approach.Apoptosis : an international journal on programmed cell death · 2022Review
- Role of lysosomes in physiological activities, diseases, and therapy.Journal of hematology & oncology · 2021Review
- Facing Cell Autophagy in Gastric Cancer - What Do We Know so Far?International journal of general medicine · 2021Review
- Potential Therapeutic Action of Autophagy in Gastric Cancer Managements: Novel Treatment Strategies and Pharmacological Interventions.Frontiers in pharmacology · 2021Review
- Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis- and autophagy-associated molecules.International journal of experimental pathology · 2020Article
- Diclofenac impairs autophagic flux via oxidative stress and lysosomal dysfunction: Implications for hepatotoxicity.Redox biology · 2020Article
- Widely available lysosome targeting agents should be considered as potential therapy for COVID-19.International journal of antimicrobial agents · 2020Article
- Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models.Antioxidants (Basel, Switzerland) · 2020Article
- Fluoxetine Simultaneously Induces Both Apoptosis and Autophagy in Human Gastric Adenocarcinoma Cells.Biomolecules & therapeutics · 2020Article
- The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?Frontiers in cell and developmental biology · 2020Review
- Regulation of Autophagy by Non-Steroidal Anti-Inflammatory Drugs in Cancer.Cancer management and research · 2020Review
- NSAIDs disrupt intestinal homeostasis by suppressing macroautophagy in intestinal epithelial cells.Scientific reports · 2019Article
- SB365,Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NSAIDs inhibit tumorigenesis in gastrointestinal tissues and have been proposed as coadjuvant agents to chemotherapy. The ability of cancer epithelial cells to adapt to the tumour environment and to resist cytotoxic agents seems to depend on rescue mechanisms such as autophagy. In the present study we aimed to determine whether an NSAID with sensitizing properties such as indomethacin modulates autophagy in gastric cancer epithelial cells. We observed that indomethacin causes lysosomal dysfunction in AGS cells and promotes the accumulation of autophagy substrates without altering mTOR activity. Indomethacin enhanced the inhibitory effects of the lysosomotropic agent chloroquine on lysosome activity and autophagy, but lacked any effect when both functions were maximally reduced with another lysosome inhibitor (bafilomycin B1). Indomethacin, alone and in combination with chloroquine, also hindered the autophagic flux stimulated by the antineoplastic drug oxaliplatin and enhanced its toxic effect, increasing the rate of apoptosis/necrosis and undermining cell viability. In summary, our results indicate that indomethacin disrupts autophagic flux by disturbing the normal functioning of lysosomes and, by doing so, increases the sensitivity of gastric cancer cells to cytotoxic agents, an effect that could be used to overcome cancer cell resistance to antineoplastic regimes.
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