ArticleJournal of cancer research and clinical oncology2011
Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation.
Article in Journal of cancer research and clinical oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism-An Unconventional Ally in Cancer Treatment.International journal of molecular sciences · 2024Review
- Targeting glucosylceramide synthase induces antiproliferative and proapoptotic effects in osimertinib-resistant NSCLC cell models.Scientific reports · 2024Article
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Development of a Novel Sphingolipid Signaling Pathway-Related Risk Assessment Model to Predict Prognosis in Kidney Renal Clear Cell Carcinoma.Frontiers in cell and developmental biology · 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
- Restoration of ceramide de novo synthesis by the synthetic retinoid ST1926 as it induces adult T-cell leukemia cell death.Bioscience reports · 2020Article
- Vaticanol C, a phytoalexin, induces apoptosis of leukemia and cancer cells by modulating expression of multiple sphingolipid metabolic enzymes.Nagoya journal of medical science · 2020Article
- Ceramide-Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations.Molecular cancer therapeutics · 2020Article
- Gaucher disease and chronic myeloid leukemia: first reported patient receiving enzyme replacement and tyrosine kinase inhibitor therapies simultaneously.Clinical case reports · 2018Article
- Targeting sphingolipid metabolism as an approach for combination therapies in haematological malignancies.Cell death discovery · 2018Article
- Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era.Advances in cancer research · 2018Review
- Translational Aspects of Sphingolipid Metabolism in Renal Disorders.International journal of molecular sciences · 2017Review
- Aneuploid Cell Survival Relies upon Sphingolipid Homeostasis.Cancer research · 2017Article
- Major apoptotic mechanisms and genes involved in apoptosis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- A molecular and biophysical comparison of macromolecular changes in imatinib-sensitive and imatinib-resistant K562 cells exposed to ponatinib.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Dynamics of ceramide generation and metabolism in response to fenretinide--Diversity within and among leukemia.Leukemia research · 2015Article
- Tamoxifen regulation of sphingolipid metabolism--Therapeutic implications.Biochimica et biophysica acta · 2015Review
- A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2015Article
- Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies.Molecules and cells · 2015Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeDrug resistance presents a major obstacle for the treatment of some patients with chronic myeloid leukemia (CML). Pro-apoptotic ceramide mediates imatinib-induced apoptosis, and metabolism of ceramide by glucosylceramide synthase (GCS) activity, converting ceramide to glucosyl ceramide, might contribute to imatinib resistance. In this study, we investigated the role of ceramide metabolism by GCS in the regulation of imatinib-induced apoptosis in drug-sensitive and drug-resistant K562 and K562/IMA-0.2 and K562/IMA-1 human CML cells, which exhibit about 2.3- and 19-fold imatinib resistance, respectively.
methodsCytotoxic effects of PDMP and imatinib were determined by XTT cell proliferation assay. Expression levels of GCS were determined by RT-PCR and western blot. Intracellular ceramide levels were determined by LC-MS. Cell viability analyses was conducted by Trypan blue dye exclusion assay. Cell cycle and apoptosis analyses were examined by flow cytometry.
resultsWe first showed that mRNA and protein levels of GCS are increased in drug-resistant K562/IMA as compared to sensitive K562 cells. Next, forced expression of GCS in sensitive K562 cells conferred resistance to imatinib-induced apoptosis. In reciprocal experiments, targeting GCS using its known inhibitor, PDMP, enhanced ceramide accumulation and increased cell death in response to imatinib in K562/IMA cells.
conclusionOur data suggest the involvement of GCS in resistance to imatinib-induced apoptosis, and that targeting GCS by PDMP increased imatinib-induced cell death in drug-sensitive and drug-resistant K562 cells via enhancing ceramide accumulation.
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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.