ArticleProceedings of the National Academy of Sciences of the United States of America2004
gamma-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 200 citations in OpenAlex.
- Pooled it
- Dietary antioxidants and prostate cancer: a review.Nutrition and cancer · 2013Pooled it
- Genetic Factors Contributing to Interindividual Variability of α-Tocopherol Levels in Subcutaneous Adipose Tissue among Healthy Adult Males.Nutrients · 2024Trial
- Natural Compounds Derived from Chilean Species and Their Cytotoxic Potential Against Cancer.Cancers · 2026Review
- Unlocking the Potential ofPlants (Basel, Switzerland) · 2025Article
- Bioactive Compounds Targeting Dihydroceramide and Their Therapeutic Potential in Cancer Treatment.Cancers · 2025Review
- Gamma-Tocopherol: A Comprehensive Review of Its Antioxidant, Anti-Inflammatory, and Anticancer Properties.Molecules (Basel, Switzerland) · 2025Review
- The Role of Vitamin E Isoforms and Metabolites in Cancer Prevention: Mechanistic Insights into Sphingolipid Metabolism Modulation.Nutrients · 2024Review
- Associations between Plasma Tocopherols and Lung Cancer Risk: Results from the Southern Community Cohort Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- A transcriptional network governing ceramide homeostasis establishes a cytokine-dependent developmental process.Nature communications · 2023Article
- Raman Spectroscopy and Imaging Studies of Human Digestive Tract Cells and Tissues-Impact of Vitamin C and E Supplementation.Molecules (Basel, Switzerland) · 2022Article
- Synergistic Interactions between Tocol and Phenolic Extracts from Different Tree Nut Species against Human Cancer Cell Lines.Molecules (Basel, Switzerland) · 2022Article
- Review
- Gamma-tocopherol, a major form of vitamin E in diets: Insights into antioxidant and anti-inflammatory effects, mechanisms, and roles in disease management.Free radical biology & medicine · 2022Article
- Utilization of redox modulating small molecules that selectively act as pro-oxidants in cancer cells to open a therapeutic window for improving cancer therapy.Redox biology · 2021Review
- Pretreatment Dietary Patterns, Serum Carotenoids and Tocopherols Influence Tumor Immune Response in Head and Neck Squamous Cell Carcinoma.Nutrition and cancer · 2021Article
- Amphiphilic Block Copolymers Bearing Hydrophobic γ-Tocopherol Groups with Labile Acetal Bond.Polymers · 2019Article
- Article
- Vitamin E δ-tocotrienol inhibits TNF-α-stimulated NF-κB activation by up-regulation of anti-inflammatory A20 via modulation of sphingolipid including elevation of intracellular dihydroceramides.The Journal of nutritional biochemistry · 2019Article
- Inhibition of mPGES-1 or COX-2 Results in Different Proteomic and Lipidomic Profiles in A549 Lung Cancer Cells.Frontiers in pharmacology · 2019Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
gamma-Tocopherol (gammaT), the predominant form of vitamin E in diets, but not alpha-tocopherol, the major vitamin E form in tissues and supplements, inhibits proliferation of prostate cancer cells (LNCaP and PC-3) and lung cancer cells (A549). In contrast, at similar concentrations, gammaT has no effect on normal prostate epithelial cells. Combinations of some vitamin E forms, such as gammaT and delta-tocopherol, exhibit additive or synergistic inhibitory effects. In this study, gammaT or its combination with delta-tocopherol induced apoptosis in androgen-sensitive prostate LNCaP, but not in androgen-resistant PC-3 cells, by the induction of cytochrome c release, activation of caspase 9 and caspase 3, cleavage of poly-ADP-ribose polymerase (PARP), and involvement of caspase-independent pathways. Myriocin and fumonisin B1, specific inhibitors of key enzymes (serine palmitoyltransferase and dihydroceramide synthase, respectively) in de novo synthesis of sphingolipids, significantly protected cells from gammaT-induced DNA fragmentation, cytochrome c release, PARP cleavage, and the formation of active caspase 3. Compared with vehicle-treated controls, gammaT treatment led to pronounced dihydroceramide and dihydrosphingosine accumulation, which preceded morphological and biochemical manifestations of apoptosis. In contrast, ceramide and shpingosine levels did not increase until day 3, when substantial cell death took place. Our study demonstrates that gammaT and mixed vitamin E forms induce cell death by interrupting the de novo sphingolipid pathway in a prostate cancer cell line. Thus, certain vitamin E forms may be valuable as anticancer agents.
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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.