ArticleOncotarget2016
P-glycoprotein-mediated chemoresistance is reversed by carbonic anhydrase XII inhibitors.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Dual-target carbonic anhydrase inhibitors in cancer therapy: progress, challenges, and opportunities.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Hybridization Approach Applied to Umbelliferon and Vanilloids toward New Inhibitors of Carbonic Anhydrases IX and XII with In Vitro Antiproliferative and Anti-inflammatory Activities.Journal of medicinal chemistry · 2026Article
- Role of Hypoxia-Associated Long Noncoding RNAs in Cancer Chemo-Therapy Resistance.International journal of molecular sciences · 2025Review
- Novel 2-Aminobenzothiazole Derivatives: Docking, Synthesis, and Biological Evaluation as Anticancer Agents.ACS omega · 2024Article
- 4-(3-Phenyl-4-(3,4,5-trimethoxybenzoyl)-1Journal of medicinal chemistry · 2023Article
- Differential CMS-Related Expression of Cell Surface Carbonic Anhydrases IX and XII in Colorectal Cancer Models-Implications for Therapy.International journal of molecular sciences · 2023Article
- Indoline-5-Sulfonamides: A Role of the Core in Inhibition of Cancer-Related Carbonic Anhydrases, Antiproliferative Activity and Circumventing of Multidrug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Article
- New Dual P-Glycoprotein (P-gp) and Human Carbonic Anhydrase XII (hCA XII) Inhibitors as Multidrug Resistance (MDR) Reversers in Cancer Cells.Journal of medicinal chemistry · 2022Article
- The complex relationship between multiple drug resistance and the tumor pH gradient: a review.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Carbonic anhydrase 12 gene silencing reverses the sensitivity of paclitaxel in drug-resistant breast cancer cells.Bioengineered · 2021Article
- Bioactive Compounds with Antiglioma Activity from Marine Species.Biomedicines · 2021Review
- Chitosan, Polyethylene Glycol and Polyvinyl Alcohol Modified MgFeMolecules (Basel, Switzerland) · 2021Article
- The Glitazone Class of Drugs as Carbonic Anhydrase Inhibitors-A Spin-Off Discovery from Fragment Screening.Molecules (Basel, Switzerland) · 2021Article
- Hybrid Drugs-A Strategy for Overcoming Anticancer Drug Resistance?Molecules (Basel, Switzerland) · 2021Review
- Carbonic anhydrase XII inhibition overcomes P-glycoprotein-mediated drug resistance: a potential new combination therapy in cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Pivarubicin Is More Effective Than Doxorubicin Against Triple-Negative Breast Cancer In Vivo.Oncology research · 2020Article
- Inhibitory Monoclonal Antibodies and Their Recombinant Derivatives Targeting Surface-Exposed Carbonic Anhydrase XII on Cancer Cells.International journal of molecular sciences · 2020Article
- Review
- Article
- Hotspots of Aberrant Enhancer Activity in Fibrolamellar Carcinoma Reveal Candidate Oncogenic Pathways and Therapeutic Vulnerabilities.Cell reports · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Carbonic anhydrase XII (CAXII) is a membrane enzyme that maintains pH homeostasis and sustains optimum P-glycoprotein (Pgp) efflux activity in cancer cells. Here, we investigated a panel of eight CAXII inhibitors (compounds 1-8), for their potential to reverse Pgp mediated tumor cell chemoresistance. Inhibitors (5 nM) were screened in human and murine cancer cells (colon, lung, breast, bone) with different expression levels of CAXII and Pgp. We identified three CAXII inhibitors (compounds 1, 2 and 4) that significantly (≥ 2 fold) increased the intracellular retention of the Pgp-substrate and chemotherapeutic doxorubicin, and restored its cytotoxic activity. The inhibitors lowered intracellular pH to indirectly impair Pgp activity. Ca12-knockout assays confirmed that the chemosensitizing property of the compounds was dependent on active CAXII. Furthermore, in a preclinical model of drug-resistant breast tumors compound 1 (1900 ng/kg) restored the efficacy of doxorubicin to the same extent as the direct Pgp inhibitor tariquidar. The expression of carbonic anhydrase IX had no effect on the intracellular doxorubicin accumulation. Our work provides strong evidence that CAXII inhibitors are effective chemosensitizer agents in CAXII-positive and Pgp-positive cancer cells. The use of CAXII inhibitors may represent a turning point in combinatorial chemotherapeutic schemes to treat multidrug-resistant tumors.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.