ArticleInternational journal of cancer2012
Gamma-tocotrienol induces apoptosis and autophagy in prostate cancer cells by increasing intracellular dihydrosphingosine and dihydroceramide.
Article in International journal of cancer, 2012. 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.
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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Pooled it
- Gamma-Tocopherol: A Comprehensive Review of Its Antioxidant, Anti-Inflammatory, and Anticancer Properties.Molecules (Basel, Switzerland) · 2025Review
- Plant-Derived Anti-Cancer Therapeutics and Biopharmaceuticals.Bioengineering (Basel, Switzerland) · 2024Review
- Sphingolipid metabolism and regulated cell death in malignant melanoma.Apoptosis : an international journal on programmed cell death · 2024Review
- The Role of Vitamin E Isoforms and Metabolites in Cancer Prevention: Mechanistic Insights into Sphingolipid Metabolism Modulation.Nutrients · 2024Review
- The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin.Scientific reports · 2023Article
- Review
- Review
- Sphingolipids in Atherosclerosis: Chimeras in Structure and Function.International journal of molecular sciences · 2022Review
- Revisiting the therapeutic potential of tocotrienol.BioFactors (Oxford, England) · 2022Review
- Nutraceuticals as Modulators of Autophagy: Relevance in Parkinson's Disease.International journal of molecular sciences · 2022Review
- Dissecting the Mechanism of Action of Spiperone-A Candidate for Drug Repurposing for Colorectal Cancer.Cancers · 2022Article
- Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase.The Journal of nutritional biochemistry · 2022Article
- The nutritional functions of dietary sphingomyelin and its applications in food.Frontiers in nutrition · 2022Review
- 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
- Molecular Insights into the Multifunctional Role of Natural Compounds: Autophagy Modulation and Cancer Prevention.Biomedicines · 2020Review
- Ligand-based discovery of small molecules suppressing cancer cell proliferation via autophagic flux inhibition.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Vitamin E and cancer: an update on the emerging role of γ and δ tocotrienols.European journal of nutrition · 2020Review
- Diversity of Chromanol and Chromenol Structures and Functions: An Emerging Class of Anti-Inflammatory and Anti-Carcinogenic Agents.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Although cell-based studies have shown that γ-tocotrienol (γTE) exhibits stronger anticancer activities than other forms of vitamin E including γ-tocopherol (γT), the molecular bases underlying γTE-exerted effects remains to be elucidated. Here we showed that γTE treatment promoted apoptosis, necrosis and autophagy in human prostate PC-3 and LNCaP cancer cells. In search of potential mechanisms of γTE-provoked effects, we found that γTE treatment led to marked increase of intracellular dihydroceramide and dihydrosphingosine, the sphingolipid intermediates in de novo sphingolipid synthesis pathway but had no effects on ceramide or sphingosine. The elevation of these sphingolipids by γTE preceded or coincided with biochemical and morphological signs of cell death and was much more pronounced than that induced by γT, which accompanied with much higher cellular uptake of γTE than γT. The importance of sphingolipid accumulation in γTE-caused fatality was underscored by the observation that dihydrosphingosine and dihydroceramide potently reduced the viability of both prostate cell lines and LNCaP cells, respectively. In addition, myriosin, a specific inhibitor of de novo sphingolipid synthesis, counteracted γTE-induced cell death. In agreement with these cell-based studies, γTE inhibited LNCaP xenograft growth by 53% (p < 0.05), compared to 33% (p = 0.07) by γT, in nude mice. These findings provide a molecular basis of γTE-stimulated cancer cell death and support the notion that elevation of intracellular dihydroceramide and dihydrosphingosine is likely a novel anticancer mechanism.
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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.