ArticleThe Journal of biological chemistry2012
Limonoid compounds inhibit sphingomyelin biosynthesis by preventing CERT protein-dependent extraction of ceramides from the endoplasmic reticulum.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- GPBP or CERT: The Roles in Autoimmunity, Cancer or Neurodegenerative Disease-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Targeting cell membrane sphingolipids: a novel ceramide analog CeY-B1 inhibits migration and invasion in cervical cancer cells.Journal of translational medicine · 2026Article
- Targeting membrane contact sites to mediate lipid dynamics: innovative cancer therapies.Cell communication and signaling : CCS · 2025Review
- Targeting ceramide transfer protein sensitizes AML to FLT3 inhibitors via a GRP78-ATF6-CHOP axis.Nature communications · 2025Article
- Non-viral Gene Therapy for Melanoma Using Lysenin from Eisenia Foetida.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.Metabolites · 2023Review
- A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients.Cancer medicine · 2023Article
- Natural Ligand-Mimetic and Nonmimetic Inhibitors of the Ceramide Transport Protein CERT.International journal of molecular sciences · 2022Review
- Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer.International journal of molecular sciences · 2021Review
- Lipid-based therapies against SARS-CoV-2 infection.Reviews in medical virology · 2021Review
- A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis.International journal of molecular sciences · 2021Review
- Biological Activities of Gedunin-A Limonoid from the Meliaceae Family.Molecules (Basel, Switzerland) · 2020Review
- Identification of the Interactions Interference Between the PH and START Domain of CERT by Limonoid and HPA Inhibitors.Frontiers in molecular biosciences · 2020Article
- Sphingolipid metabolism in cancer signalling and therapy.Nature reviews. Cancer · 2018Review
- 25-Hydroxycholesterol activates the integrated stress response to reprogram transcription and translation in macrophages.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To identify novel inhibitors of sphingomyelin (SM) metabolism, a new and selective high throughput microscopy-based screening based on the toxicity of the SM-specific toxin, lysenin, was developed. Out of a library of 2011 natural compounds, the limonoid, 3-chloro-8β-hydroxycarapin-3,8-hemiacetal (CHC), rendered cells resistant to lysenin by decreasing cell surface SM. CHC treatment selectively inhibited the de novo biosynthesis of SM without affecting glycolipid and glycerophospholipid biosynthesis. Pretreatment with brefeldin A abolished the limonoid-induced inhibition of SM synthesis suggesting that the transport of ceramide (Cer) from the endoplasmic reticulum to the Golgi apparatus is affected. Unlike the Cer transporter (CERT) inhibitor HPA-12, CHC did not change the transport of a fluorescent short chain Cer analog to the Golgi apparatus or the formation of fluorescent and short chain SM from the corresponding Cer. Nevertheless, CHC inhibited the conversion of de novo synthesized Cer to SM. We show that CHC specifically inhibited the CERT-mediated extraction of Cer from the endoplasmic reticulum membranes in vitro. Subsequent biochemical screening of 21 limonoids revealed that some of them, such as 8β-hydroxycarapin-3,8-hemiacetal and gedunin, which exhibits anti-cancer activity, inhibited SM biosynthesis and CERT-mediated extraction of Cer from membranes. Model membrane studies suggest that 8β-hydroxycarapin-3,8-hemiacetal reduced the miscibility of Cer with membrane lipids and thus induced the formation of Cer-rich membrane domains. Our study shows that certain limonoids are novel inhibitors of SM biosynthesis and suggests that some biological activities of these limonoids are related to their effect on the ceramide metabolism.
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Registered trials
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