ArticleProceedings of the National Academy of Sciences of the United States of America2011
Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.
- Decreased sphingomyelin (t34:1) is a candidate predictor for lung squamous cell carcinoma recurrence after radical surgery: a case-control study.BMC cancer · 2021Pooled it
- A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma.British journal of cancer · 2023Trial
- Statins in Membrane Lipid Therapy: Mechanistic Promise Versus Clinical Reality.International journal of molecular sciences · 2026Article
- Differentiation of sphingomyelin and cholesterol by hyperspectral mid-infrared detection of single-bond vibrational modes in the fingerprint region.Nature methods · 2026Article
- Restoring B cell intrinsic tolerance to lupus autoimmunity: a rational strategy for lupus treatment.Frontiers in immunology · 2026Review
- The causal effects of 1400 genetically determined human blood metabolites and metabolite ratios on the risk of gastrointestinal tumors: a Mendelian randomization study.Archives of medical science : AMS · 2026Article
- Review
- An Insight into Cancer Cells and Disease Progression Through the Lens of Mathematical Modeling.Current issues in molecular biology · 2025Review
- Targeting gut microbiota: a potential therapeutic approach for tumor microenvironment in glioma.Frontiers in neurology · 2025Review
- Precise Identification of Glioblastoma Micro-Infiltration at Cellular Resolution by Raman Spectroscopy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Investigating the impact of 2-OHOA-embedded liposomes on biophysical properties of cancer cell membranes via Laurdan two-photon microscopy imaging.Scientific reports · 2024Article
- PKCδ Protects against Lupus Autoimmunity.Biomedicines · 2024Review
- Tumor-Homing Peptides as Crucial Component of Magnetic-Based Delivery Systems: Recent Developments and Pharmacoeconomical Perspective.International journal of molecular sciences · 2024Review
- Review
- 2-Hydroxyoleic Acid as a Self-Assembly Inducer for Anti-Cancer Drug-Centered Nanoparticles.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Evolving Diagnostic and Treatment Strategies for Pediatric CNS Tumors: The Impact of Lipid Metabolism.Biomedicines · 2023Review
- Molecular profiling of the stroke-induced alterations in the cerebral microvasculature reveals promising therapeutic candidates.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Antitumor Effect of Iscador on Breast Cancer Cell Lines with Different Metastatic Potential.International journal of molecular sciences · 2023Article
- Mechanisms of Arachidonic Acid In Vitro Tumoricidal Impact.Molecules (Basel, Switzerland) · 2023Article
- Comprehensive serum lipidomic analyses reveal potential biomarkers for malignant breast cancer: A case-control study.Cancer biomarkers : section A of Disease markers · 2023Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor compound, has not yet been fully elucidated. Here, we show that human cancer cells have markedly lower levels of sphingomyelin (SM) than nontumor (MRC-5) cells. In this context, 2OHOA treatment strongly augments SM mass (4.6-fold), restoring the levels found in MRC-5 cells, while a loss of phosphatidylethanolamine and phosphatidylcholine is observed (57 and 30%, respectively). The increased SM mass was due to a rapid and highly specific activation of SM synthases (SMS). This effect appeared to be specific against cancer cells as it did not affect nontumor MRC-5 cells. Therefore, low SM levels are associated with the tumorigenic transformation that produces cancer cells. SM accumulation occurred at the plasma membrane and caused an increase in membrane global order and lipid raft packing in model membranes. These modifications would account for the observed alteration by 2OHOA in the localization of proteins involved in cell apoptosis (Fas receptor) or differentiation (Ras). Importantly, SMS inhibition by D609 diminished 2OHOA effect on cell cycle. Therefore, we propose that the regulation of SMS activity in tumor cells is a critical upstream event in 2OHOA antitumor mechanism, which also explains its specificity for cancer cells, its potency, and the lack of undesired side effects. Finally, the specific activation of SMS explains the ability of this compound to trigger cell cycle arrest, cell differentiation, and autophagy or apoptosis in cancer cells.
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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.