ArticleOncotarget2013
Cell death sensitization of leukemia cells by opioid receptor activation.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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Who cites it
31 citing papers in PubMed, 73 citations in OpenAlex.
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- 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
- Methadone Requires the Co-Activation of μ-Opioid and Toll-Like-4 Receptors to Produce Extracellular DNA Traps in Bone-Marrow-Derived Mast Cells.International journal of molecular sciences · 2024Article
- Insufficient autophagy enables the nuclear factor erythroid 2-related factor 2 (NRF2) to promote ferroptosis in morphine-treated SH-SY5Y cells.Psychopharmacology · 2024Article
- PKA inhibition is a central step in D,L-methadone-induced ER CaFrontiers in cell and developmental biology · 2024Article
- Article
- Mapping the Evidence for Opioid-Mediated Changes in Malignancy and Chemotherapeutic Efficacy: Protocol for a Scoping Review.JMIR research protocols · 2023Article
- D,L-Methadone enhances the cytotoxic activity of standard chemotherapeutic agents on pediatric rhabdomyosarcoma.Journal of cancer research and clinical oncology · 2022Article
- Less Well-Known Consequences of the Long-Term Use of Opioid Analgesics: A Comprehensive Literature Review.Drug design, development and therapy · 2022Review
- Anaesthesia as an influence in tumour progression.Langenbeck's archives of surgery · 2021Review
- The role of methadone in cancer-induced bone pain: a retrospective cohort study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021Article
- Methadone-mediated sensitization of glioblastoma cells is drug and cell line dependent.Journal of cancer research and clinical oncology · 2021Article
- D,L-Methadone causes leukemic cell apoptosis via an OPRM1-triggered increase in IP3R-mediated ER CaScientific reports · 2021Article
- Cytotoxic and Senolytic Effects of Methadone in Combination with Temozolomide in Glioblastoma Cells.International journal of molecular sciences · 2020Article
- Impact of Opioid Use in Hematological Malignancies: Clinical, Immunological and Concomitant Aspects.Journal of hematology · 2020Review
- Methadone does not potentiate the effect of doxorubicin in canine tumour cell lines.Veterinary medicine and science · 2020Article
- Against Repurposing Methadone for Glioblastoma Therapy.Biomolecules · 2020Review
- Targeting cyclooxygenase by indomethacin decelerates progression of acute lymphoblastic leukemia in a xenograft model.Blood advances · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies.
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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.