ArticleCell & bioscience2014
Induction of ER stress-mediated apoptosis by ceramide via disruption of ER Ca(2+) homeostasis in human adenoid cystic carcinoma cells.
Article in Cell & bioscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Pooled it
- Ceramide: a pivotal lipid mediator shaping female reproductive homeostasis and pathophysiology.Journal of ovarian research · 2026Review
- Synergistic Molecular Strategies for Targeting the Unfolded Protein Response in Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Curcumin as a ceramide metabolism-targeting agent: Molecular mechanisms and therapeutic implications in cancer.Molecular biology reports · 2026Review
- Acid Ceramidase Inhibition Disrupts Ceramide Homeostasis and Induces Mitochondrial Apoptosis in IDH1-Mutant Oligodendroglioma.Research square · 2026Article
- GATA2 deficiency exacerbates chronic liver injuryWorld journal of stem cells · 2026Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Ceramide mediates cell-to-cell ER stress transmission by modulating membrane fluidity.The Journal of cell biology · 2025Article
- Metabolomics insights into the protective molecular mechanism of Vaccinium myrtillus against oxidative stress in intestinal cells.Scientific reports · 2025Article
- Acid Sphingomyelinase Regulates AdipoRon-Induced Differentiation of Arterial Smooth Muscle Cells via TFEB Activation.International journal of molecular sciences · 2025Article
- The Protective Effect of Nimodipine in Schwann Cells Is Related to the Upregulation of LMO4 and SERCA3 Accompanied by the Fine-Tuning of Intracellular Calcium Levels.International journal of molecular sciences · 2025Article
- Two-Step Cell Death Induction by the New 2-Arachidonoyl Glycerol Analog and Its Modulation by Lysophosphatidylinositol in Human Breast Cancer Cells.International journal of molecular sciences · 2025Article
- The Interplay between Oxidative Stress and Sphingolipid Metabolism in Endometrial Cancer.International journal of molecular sciences · 2024Article
- Article
- Tauroursodeoxycholic Acid (TUDCA) Relieves Streptozotocin (STZ)-Induced Diabetic Rat Model via Modulation of Lipotoxicity, Oxidative Stress, Inflammation, and Apoptosis.International journal of molecular sciences · 2024Article
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- Blocking lipid synthesis induces DNA damage in prostate cancer and increases cell death caused by PARP inhibition.Science signaling · 2024Article
- Untargeted and temporal analysis of retinal lipidome in bacterial endophthalmitis.Prostaglandins & other lipid mediators · 2024Review
- Fine-tuned protein-lipid interactions in biological membranes: exploration and implications of the ORMDL-ceramide negative feedback loop in the endoplasmic reticulum.Frontiers in cell and developmental biology · 2024Article
- Transcriptional suppression of sphingolipid catabolism controls pathogen resistance in C. elegans.PLoS pathogens · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCeramides are a class of sphingolipids that form the structural component of the cell membrane and also act as second messengers in cell signaling pathways. Emerging results suggest that ceramide induces growth arrest and apoptosis in various human cancer cells. However, the mechanisms underlying its antitumor activity are yet to be identified. Endoplasmic reticulum stress (ER stress), a cellular adaptive response, is believed to initially compensate for damage but can eventually trigger cell death if the stimulus is severe or prolonged. In this study, we investigated whether ceramide induces cell death in human salivary adenoid cystic carcinoma (ACCs) through activation of the apoptotic ER stress.
resultsRT-PCR, real-time PCR and western blot demonstrated that exogenous ceramide treatment up-regulated GRP78 and p-eIF2α expression and XBP1 splicing. Moreover, the ceramide synthase inhibitor FB1 abolished ceramide-induced ER stress. Up-regulation of the ER stress-associated apoptosis promoting transcription factor CHOP and p-JNK suggested that the antitumor activity of ceramide is owing to activation of apoptotic ER stress. Mechanistically, [Ca(2+)]ER depletion and SERCA inhibition by ceramide treatment suggested that it induces ER stress by disrupting [Ca(2+)]ER homeostasis. The chemical chaperone TUDCA inhibited ceramide-induced ER stress and cell death. In addition, the downstream metabolite of ceramide, S1P, cannot activate ER stress.
conclusionsThese results demonstrated that exogenous ceramide induces cancer cell death through a mechanism involving severe ER stress triggered by the disruption of ER Ca(2+) homeostasis.
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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.