ArticleThe Biochemical journal2003
Inhibitors of vacuolar H+-ATPase impair the preferential accumulation of daunomycin in lysosomes and reverse the resistance to anthracyclines in drug-resistant renal epithelial cells.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 98 citations in OpenAlex.
- Recent progress in small molecules targeting the acidic tumor microenvironment.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- A protracted war against cancer drug resistance.Cancer cell international · 2024Review
- Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy.Pharmaceutics · 2024Review
- UNC13B regulates the sensitivity of Wilms' tumor cells to doxorubicin by modulating lysosomes.Oncology letters · 2024Article
- Proton pump inhibitors display anti-tumour potential in glioma.Cell proliferation · 2023Review
- Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases.Biomedicines · 2022Article
- Article
- Regulation and function of V-ATPases in physiology and disease.Biochimica et biophysica acta. Biomembranes · 2020Review
- Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance.Cancers · 2020Review
- Regulating Interactions Between Targeted Nanocarriers and Mononuclear Phagocyte System via an Esomeprazole-Based Preconditioning Strategy.International journal of nanomedicine · 2020Article
- Influence of lysosomal sequestration on multidrug resistance in cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Dual role of HDAC10 in lysosomal exocytosis and DNA repair promotes neuroblastoma chemoresistance.Scientific reports · 2018Article
- Tumor microenvironment interruption: a novel anti-cancer mechanism of Proton-pump inhibitor in gastric cancer by suppressing the release of microRNA-carrying exosomes.American journal of cancer research · 2017Article
- Role of autophagy and lysosomal drug sequestration in acquired resistance to doxorubicin in MCF-7 cells.BMC cancer · 2016Article
- Identification of V-ATPase as a molecular sensor of SOX11-levels and potential therapeutic target for mantle cell lymphoma.BMC cancer · 2016Article
- The Function of V-ATPases in Cancer.Physiological reviews · 2016Review
- Enhancement of Small Molecule Delivery by Pulsed High-Intensity Focused Ultrasound: A Parameter Exploration.Ultrasound in medicine & biology · 2016Article
- Molecular Determinants of GS-9620-Dependent TLR7 Activation.PloS one · 2016Article
- Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1.Cancers · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been suggested that the inappropriate sequestration of weak-base chemotherapeutic drugs in acidic vesicles by multidrug-resistance (MDR) cells contributes to the mechanisms of drug resistance. The function of the acidic lysosomes can be altered in MDR cells, and so we investigated the effects of lysosomotropic agents on the secretion of lysosomal enzymes and on the intracellular distribution of the weak-base anthracycline daunomycin in drug-resistant renal proximal tubule PKSV-PR(col50) cells and their drug-sensitive PKSV-PR cell counterparts. Imaging studies using pH-dependent lysosomotropic dyes revealed that drug-sensitive and drug-resistant cells exhibited a similar acidic lysosomal pH (around 5.6-5.7), but that PKSV-PR(col50) cells contained more acidic lysosomes and secreted more of the lysosomal enzymes N -acetyl-beta-hexosaminidase and beta-glucuronidase than their parent PKSV-PR cells. Concanamycin A (CCM A), a potent inhibitor of the vacuolar H(+)-ATPase, but not the P-glycoprotein modulator verapamil, stimulated the secretion of N -acetyl-beta-hexosaminidase in both drug-sensitive and drug-resistant cells. Fluorescent studies and Percoll density gradient fractionation studies revealed that daunomycin accumulated predominantly in the lysosomes of PKSV-PR(col50) cells, whereas in PKSV-PR cells the drug was distributed evenly throughout the nucleo-cytoplasmic compartments. CCM A did not impair the cellular efflux of daunomycin, but induced the rapid nucleo-cytoplasmic redistribution of the drug in PKSV-PR(col50) cells. In addition, CCM A and bafilomycin A1 almost completely restored the sensitivity of these drug-resistant cells to daunomycin, doxorubicin and epirubicin. These findings indicate that lysosomotropic agents that impair the acidic-pH-dependent accumulation of weak-base chemotherapeutic drugs may reverse anthracycline resistance in MDR cells with an expanded acidic lysosomal compartment.
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