ArticlePloS one2009
A new mixed-backbone oligonucleotide against glucosylceramide synthase sensitizes multidrug-resistant tumors to apoptosis.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers.Biomolecules · 2025Review
- The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism-An Unconventional Ally in Cancer Treatment.International journal of molecular sciences · 2024Review
- Blockade of Glycosphingolipid Synthesis Inhibits Cell Cycle and Spheroid Growth of Colon Cancer Cells In Vitro and Experimental Colon Cancer Incidence In Vivo.International journal of molecular sciences · 2021Article
- Cancer stem cells and ceramide signaling: the cutting edges of immunotherapy.Molecular biology reports · 2020Review
- Review
- Ceramide-Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations.Molecular cancer therapeutics · 2020Article
- Role of Glucosylceramide in Lung Endothelial Cell Fate and Emphysema.American journal of respiratory and critical care medicine · 2019Article
- Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era.Advances in cancer research · 2018Review
- Inhibition of hepatocellular carcinoma growth by blockade of glycosphingolipid synthesis.Oncotarget · 2017Article
- A peptidomimetic with a chiral switch is an inhibitor of epidermal growth factor receptor heterodimerization.Oncotarget · 2017Article
- Incorporation of Fluorescence Ceramide-Based HPLC Assay for Rapidly and Efficiently Assessing Glucosylceramide Synthase In Vivo.Scientific reports · 2017Article
- Microbubble-based enhancement of radiation effect: Role of cell membrane ceramide metabolism.PloS one · 2017Article
- Article
- An increase in glucosylceramide synthase induces Bcl-xL-mediated cell survival in vinorelbine-resistant lung adenocarcinoma cells.Oncotarget · 2015Article
- Novel Peptidomimetics for Inhibition of HER2:HER3 Heterodimerization in HER2-Positive Breast Cancer.Chemical biology & drug design · 2015Article
- Glucosylceramide synthase promotes Bcl-2 expression via the ERK signaling pathway in the K562/A02 leukemia drug-resistant cell line.International journal of hematology · 2014Article
- Ceramide modulates pre-mRNA splicing to restore the expression of wild-type tumor suppressor p53 in deletion-mutant cancer cells.Biochimica et biophysica acta · 2014Article
- Re-configuration of sphingolipid metabolism by oncogenic transformation.Biomolecules · 2014Review
- 3-Ketone-4,6-diene ceramide analogs exclusively induce apoptosis in chemo-resistant cancer cells.Bioorganic & medicinal chemistry · 2014Article
- New Insights on Glucosylceramide Synthase in Cancer Drug Resistance and Myelosuppression.Biochemistry & pharmacology : open access · 2013Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) limits therapeutic efficiencies of antineoplastic agents including doxorubicin in drug-resistant cancer cells. Aimed to determine the role of GCS in tumor response to chemotherapy, a new mixed-backbone oligonucleotide (MBO-asGCS) with higher stability and efficiency has been generated to silence human GCS gene. MBO-asGCS was taken up efficiently in both drug-sensitive and drug-resistant cells, but it selectively suppressed GCS overexpression, and sensitized drug-resistant cells. MBO-asGCS increased doxorubicin sensitivity by 83-fold in human NCI/ADR-RES, and 43-fold in murine EMT6/AR1 breast cancer cells, respectively. In tumor-bearing mice, MBO-asGCS treatment dramatically inhibited the growth of multidrug-resistant NCI/ADR-RE tumors, decreasing tumor volume to 37%, as compared with scrambled control. Furthermore, MBO-asGCS sensitized multidrug-resistant tumors to chemotherapy, increasing doxorubicin efficiency greater than 2-fold. The sensitization effects of MBO-asGCS relied on the decreases of gene expression and enzyme activity of GCS, and on the increases of C(18)-ceramide and of caspase-executed apoptosis. MBO-asGCS was accumulation in tumor xenografts was greater in other tissues, excepting liver and kidneys; but MBO-asGCS did not exert significant toxic effects on liver and kidneys. This study, for the first time in vivo, has demonstrated that GCS is a promising therapeutic target for cancer drug resistance, and MBO-asGCS has the potential to be developed as an antineoplastic agent.
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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.