ArticleCell cycle (Georgetown, Tex.)2014
Opioid receptor activation triggering downregulation of cAMP improves effectiveness of anti-cancer drugs in treatment of glioblastoma.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- Oncohistone inhibition reshapes tumor-microenvironment communication in Diffuse Midline Glioma (DMG).bioRxiv : the preprint server for biology · 2026Article
- Investigation of the impact of D, L-methadone on ALA-PDT in multiple glioblastoma cell lines.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Article
- Cell-Specific Vulnerability of Human Glioblastoma and Astrocytoma Cells to Mephedrone-An In Vitro Study.Molecules (Basel, Switzerland) · 2025Article
- L-asparaginase induces IP3R-mediated ER CaCell death discovery · 2024Article
- PKA inhibition kills L-asparaginase-resistant leukemic cells from relapsed acute lymphoblastic leukemia patients.Cell death discovery · 2024Article
- Anesthesia and cancer recurrence: a narrative review.Anesthesia and pain medicine · 2024Review
- Antineoplastic Activity of 9″-Lithospermic Acid Methyl Ester in Glioblastoma Cells.International journal of molecular sciences · 2024Article
- Article
- Mapping the Evidence for Opioid-Mediated Changes in Malignancy and Chemotherapeutic Efficacy: Protocol for a Scoping Review.JMIR research protocols · 2023Article
- Does the Choice of Anaesthesia Affect Cancer? A Molecular Crosstalk between Theory and Practice.Cancers · 2022Review
- Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments.Pharmaceutics · 2022Article
- Osteoarthritis-Induced Metabolic Alterations of Human Hip Chondrocytes.Biomedicines · 2022Article
- D,L-Methadone enhances the cytotoxic activity of standard chemotherapeutic agents on pediatric rhabdomyosarcoma.Journal of cancer research and clinical oncology · 2022Article
- Spoken and Unspoken Matters Regarding the Use of Opioids in Cancer.Journal of pain research · 2022Review
- Less Well-Known Consequences of the Long-Term Use of Opioid Analgesics: A Comprehensive Literature Review.Drug design, development and therapy · 2022Review
- MethylSPWNet and MethylCapsNet: Biologically Motivated Organization of DNAm Neural Networks, Inspired by Capsule Networks.NPJ systems biology and applications · 2021Article
- Targeting the mu-Opioid Receptor for Cancer Treatment.Current oncology reports · 2021Review
- Anaesthesia as an influence in tumour progression.Langenbeck's archives of surgery · 2021Review
- Methadone-mediated sensitization of glioblastoma cells is drug and cell line dependent.Journal of cancer research and clinical oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma are the most frequent and malignant human brain tumors, having a very poor prognosis. The enhanced radio- and chemoresistance of glioblastoma and the glioblastoma stem cells might be the main reason why conventional therapies fail. The second messenger cyclic AMP (cAMP) controls cell proliferation, differentiation, and apoptosis. Downregulation of cAMP sensitizes tumor cells for anti-cancer treatment. Opioid receptor agonists triggering opioid receptors can activate inhibitory Gi proteins, which, in turn, block adenylyl cyclase activity reducing cAMP. In this study, we show that downregulation of cAMP by opioid receptor activation improves the effectiveness of anti-cancer drugs in treatment of glioblastoma. The µ-opioid receptor agonist D,L-methadone sensitizes glioblastoma as well as the untreatable glioblastoma stem cells for doxorubicin-induced apoptosis and activation of apoptosis pathways by reversing deficient caspase activation and deficient downregulation of XIAP and Bcl-xL, playing critical roles in glioblastomas' resistance. Blocking opioid receptors using the opioid receptor antagonist naloxone or increasing intracellular cAMP by 3-isobutyl-1-methylxanthine (IBMX) strongly reduced opioid receptor agonist-induced sensitization for doxorubicin. In addition, the opioid receptor agonist D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux, whereas doxorubicin increased opioid receptor expression in glioblastomas. Furthermore, opioid receptor activation using D,L-methadone inhibited tumor growth significantly in vivo. Our findings suggest that opioid receptor activation triggering downregulation of cAMP is a promising strategy to inhibit tumor growth and to improve the effectiveness of anti-cancer drugs in treatment of glioblastoma and in killing glioblastoma stem cells.
Indexed as
Identifiers
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.