ArticleMolecular pharmacology2012
Xanthines down-regulate the drug transporter ABCG2 and reverse multidrug resistance.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Genetic susceptibility to caffeine intake and metabolism: a systematic review.Journal of translational medicine · 2024Pooled it
- Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf.Pharmaceuticals (Basel, Switzerland) · 2025Review
- ATP-Binding Cassette Subfamily G Member 2 in Acute Myeloid Leukemia: A New Molecular Target?Biomedicines · 2024Review
- Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin.International journal of oncology · 2023Article
- Heterogeneous network propagation with forward similarity integration to enhance drug-target association prediction.PeerJ. Computer science · 2022Article
- The Discovery of New Drug-Target Interactions for Breast Cancer Treatment.Molecules (Basel, Switzerland) · 2021Article
- Multidrug efflux transporter ABCG2: expression and regulation.Cellular and molecular life sciences : CMLS · 2021Review
- Potential Herb-Drug Interactions in the Management of Age-Related Cognitive Dysfunction.Pharmaceutics · 2021Review
- Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids.Frontiers in pharmacology · 2021Review
- Review
- SLAMF1 Promotes Methotrexate Resistance via Activating Autophagy in Choriocarcinoma Cells.Cancer management and research · 2020Article
- Quantitative Proteomic Profiling Identifies SOX8 as Novel Regulator of Drug Resistance in Gestational Trophoblastic Neoplasia.Frontiers in oncology · 2020Article
- Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.Frontiers in oncology · 2020Article
- Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10.Journal of Cancer · 2018Article
- A role for ABCG2 beyond drug transport: Regulation of autophagy.Autophagy · 2016Article
- New trends for overcoming ABCG2/BCRP-mediated resistance to cancer therapies.Journal of experimental & clinical cancer research : CR · 2015Review
- Effect ofMolecular and clinical oncology · 2015Article
- Article
- Human ABCG2: structure, function, and its role in multidrug resistance.International journal of biochemistry and molecular biology · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
ABCG2 is an ATP-binding-cassette (ABC) transporter that confers multidrug resistance (MDR) to tumor cells by extruding a broad variety of chemotherapeutic agents, ultimately leading to failure of cancer therapy. Thus, the down-regulation of ABCG2 expression and/or function has been proposed as part of a regimen to improve cancer therapeutic efficacy. In this study, we found that a group of xanthines including caffeine, theophylline, and dyphylline can dramatically decrease ABCG2 protein in cells that have either moderate (BeWo, a placental choriocarcinoma cell line) or high (MCF-7/MX100, a breast cancer drug-resistant cell subline) levels of ABCG2 expression. This down-regulation is time-dependent, dose-dependent, and reversible. Using lysosomal inhibitors, we found that xanthines decreased ABCG2 by inducing its rapid internalization and lysosome-mediated degradation. As a consequence, caffeine treatment significantly increased the retention of an established ABCG2 substrate in MCF-7/MX100 cells but not in parental MCF-7 cells and sensitized the MDR cells to the chemotherapeutic agent mitoxantrone (MX); combination treatment with MX and caffeine decreased the IC(50) of MX ~10-fold and induced a greater degree of apoptotic cell death than MX treatment alone. Taken together, our results describe a novel function for this large class of therapeutically relevant compounds and suggest that a subset of xanthines could be developed as combination therapy to improve the efficacy of anticancer drugs that are ABCG2 substrates.
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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.