ArticleCellular and molecular life sciences : CMLS2014
Temozolomide down-regulates P-glycoprotein in human blood-brain barrier cells by disrupting Wnt3 signaling.
Article in Cellular and molecular life sciences : CMLS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 59 citations in OpenAlex.
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- Association Between MGMT Promoter Methylation and Clinical and Lifestyle Factors in Glioblastoma: A Single-Center Study in Korea.Journal of clinical medicine · 2026Article
- Exploration of the Neuromodulatory Properties of Fyn and GSK-3β Kinases Exploiting 7-Azaindole-Based Inhibitors.Journal of medicinal chemistry · 2025Article
- Engineering Multifunctional Peptide-Decorated Nanofibers for Targeted Delivery of Temozolomide across the Blood-Brain Barrier.Molecular pharmaceutics · 2025Article
- Revisiting ABC Transporters and Their Clinical Significance in Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery.Circulation research · 2024Review
- Regulation of P-Glycoprotein in the Brain.International journal of molecular sciences · 2022Review
- Recent Development in NKT-Based Immunotherapy of Glioblastoma: From Bench to Bedside.International journal of molecular sciences · 2022Review
- Estrogen Receptors as Molecular Targets of Endocrine Therapy for Glioblastoma.International journal of molecular sciences · 2021Review
- Circulating microRNA: The Potential Novel Diagnostic Biomarkers to Predict Drug Resistance in Temporal Lobe Epilepsy, a Pilot Study.International journal of molecular sciences · 2021Article
- Mifepristone Repurposing in Treatment of High-Grade Gliomas.Frontiers in oncology · 2021Review
- RPN2 is targeted by miR-181c and mediates glioma progression and temozolomide sensitivity via the wnt/β-catenin signaling pathway.Cell death & disease · 2020Article
- Development of a human in vitro blood-brain tumor barrier model of diffuse intrinsic pontine glioma to better understand the chemoresistance.Fluids and barriers of the CNS · 2020Article
- Identification of GSK3β inhibitor kenpaullone as a temozolomide enhancer against glioblastoma.Scientific reports · 2019Article
- Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.Nature communications · 2019Article
- Flavonoids modulate multidrug resistance through wnt signaling in P-glycoprotein overexpressing cell lines.BMC cancer · 2018Article
- Down-regulation of MDR1 by Ad-DKK3 via Akt/NFκB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model.Journal of neuro-oncology · 2018Article
- New Tetrahydroisoquinoline Derivatives Overcome Pgp Activity in Brain-Blood Barrier and Glioblastoma Multiforme in Vitro.Molecules (Basel, Switzerland) · 2018Article
- MicroRNA-298 Reverses Multidrug Resistance to Antiepileptic Drugs by Suppressing MDR1/P-gp ExpressionFrontiers in neuroscience · 2018Article
- Discovery of Klotho peptide antagonists against Wnt3 and Wnt3a target proteins using combination of protein engineering, protein-protein docking, peptide docking and molecular dynamics simulations.Journal of enzyme inhibition and medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low delivery of many anticancer drugs across the blood-brain barrier (BBB) is a limitation to the success of chemotherapy in glioblastoma. This is because of the high levels of ATP-binding cassette transporters like P-glycoprotein (Pgp/ABCB1), which effluxes drugs back to the bloodstream. Temozolomide is one of the few agents able to cross the BBB; its effects on BBB cells permeability and Pgp activity are not known. We found that temozolomide, at therapeutic concentration, increased the transport of Pgp substrates across human brain microvascular endothelial cells and decreased the expression of Pgp. By methylating the promoter of Wnt3 gene, temozolomide lowers the endogenous synthesis of Wnt3 in BBB cells, disrupts the Wnt3/glycogen synthase kinase 3/β-catenin signaling, and reduces the binding of β-catenin on the promoter of mdr1 gene, which encodes for Pgp. In co-culture models of BBB cells and human glioblastoma cells, pre-treatment with temozolomide increases the delivery, cytotoxicity, and antiproliferative effects of doxorubicin, vinblastine, and topotecan, three substrates of Pgp that are usually poorly delivered across BBB. Our work suggests that temozolomide increases the BBB permeability of drugs that are normally effluxed by Pgp back to the bloodstream. These findings may pave the way to new combinatorial chemotherapy schemes in glioblastoma.
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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.