ArticleJournal of lipid research2016
Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia.
Article in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- C6 Ceramide Inhibits Canine Mammary Cancer Growth and Metastasis by Targeting EGR3 through JAK1/STAT3 Signaling.Animals : an open access journal from MDPI · 2024Article
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- Article
- Intrinsic adaptations in OXPHOS power output and reduced tumorigenicity characterize doxorubicin resistant ovarian cancer cells.Biochimica et biophysica acta. Bioenergetics · 2022Article
- Article
- Harnessing the power of sphingolipids: Prospects for acute myeloid leukemia.Blood reviews · 2022Review
- Ceramide-induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia.Blood · 2022Article
- Ceramide: improving Bcl-2 inhibitor therapy.Blood · 2022Article
- Alterations in sphingolipid composition and mitochondrial bioenergetics represent synergistic therapeutic vulnerabilities linked to multidrug resistance in leukemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- C6-ceramide treatment inhibits the proangiogenic activity of multiple myeloma exosomes via the miR-29b/Akt pathway.Journal of translational medicine · 2020Article
- Review
- Utilizing Synergistic Potential of Mitochondria-Targeting Drugs for Leukemia Therapy.Frontiers in oncology · 2020Article
- Chemotherapy selection pressure alters sphingolipid composition and mitochondrial bioenergetics in resistant HL-60 cells.Journal of lipid research · 2019Article
- Pivotal role of mitophagy in response of acute myelogenous leukemia to a ceramide-tamoxifen-containing drug regimen.Experimental cell research · 2019Article
- Clinical application of ceramide in cancer treatment.Breast cancer (Tokyo, Japan) · 2019Review
- Targeting sphingolipid metabolism as an approach for combination therapies in haematological malignancies.Cell death discovery · 2018Article
- Incorporation of Fluorescence Ceramide-Based HPLC Assay for Rapidly and Efficiently Assessing Glucosylceramide Synthase In Vivo.Scientific reports · 2017Article
- The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia.Expert opinion on therapeutic targets · 2017Review
- Role of P-glycoprotein inhibitors in ceramide-based therapeutics for treatment of cancer.Biochemical pharmacology · 2017Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
The objective of our study was to determine the mechanism of action of the short-chain ceramide analog, C6-ceramide, and the breast cancer drug, tamoxifen, which we show coactively depress viability and induce apoptosis in human acute myelogenous leukemia cells. Exposure to the C6-ceramide-tamoxifen combination elicited decreases in mitochondrial membrane potential and complex I respiration, increases in reactive oxygen species (ROS), and release of mitochondrial proapoptotic proteins. Decreases in ATP levels, reduced glycolytic capacity, and reduced expression of inhibitors of apoptosis proteins also resulted. Cytotoxicity of the drug combination was mitigated by exposure to antioxidant. Cells metabolized C6-ceramide by glycosylation and hydrolysis, the latter leading to increases in long-chain ceramides. Tamoxifen potently blocked glycosylation of C6-ceramide and long-chain ceramides. N-desmethyltamoxifen, a poor antiestrogen and the major tamoxifen metabolite in humans, was also effective with C6-ceramide, indicating that traditional antiestrogen pathways are not involved in cellular responses. We conclude that cell death is driven by mitochondrial targeting and ROS generation and that tamoxifen enhances the ceramide effect by blocking its metabolism. As depletion of ATP and targeting the "Warburg effect" represent dynamic metabolic insult, this ceramide-containing combination may be of utility in the treatment of leukemia and other cancers.
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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.