ArticleOncotarget2014
Y-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 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
85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- Effects of Tocotrienol-Rich Fraction Supplementation in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Advances in nutrition (Bethesda, Md.) · 2023Pooled it
- Systematic review and meta-analysis of the prognostic significance of microRNAs related to metastatic and EMT process among prostate cancer patients.Journal of translational medicine · 2021Pooled it
- γ-Tocotrienol inhibits HeLa cell proliferation likely via modulation of the PI3K/AKT/mTOR signaling pathway.Frontiers in nutrition · 2026Article
- Antioxidant Food Supplementation in Cancer: Lessons from Clinical Trials and Insights from Preclinical Studies.Antioxidants (Basel, Switzerland) · 2025Review
- Effectiveness of Tocotrienol-Rich Fraction in Older Adults: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial.JMIR research protocols · 2025Article
- Kinase signaling cascades: an updated mechanistic landscape.Chemical science · 2025Review
- Gamma-tocotrienol Inhibits Proliferation and Growth of HSD17B4 Overexpressing HepG2 Liver Cancer Cells.Current cancer drug targets · 2025Article
- Anticancer Activity of Delta-Tocotrienol in Human Hepatocarcinoma: Involvement of Autophagy Induction.Cancers · 2024Article
- Hypoxia signaling in hepatocellular carcinoma: Challenges and therapeutic opportunities.Cancer metastasis reviews · 2023Review
- PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.Molecular cancer · 2023Review
- Tocotrienol-rich fraction reduces retinal inflammation and angiogenesis in rats with streptozotocin-induced diabetes.BMC complementary medicine and therapies · 2023Article
- E7050 Suppresses the Growth of Multidrug-Resistant Human Uterine Sarcoma by Inhibiting Angiogenesis via Targeting of VEGFR2-Mediated Signaling Pathways.International journal of molecular sciences · 2023Article
- Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal PlantPharmaceuticals (Basel, Switzerland) · 2023Review
- Cucurbitacins as Potent Chemo-Preventive Agents: Mechanistic Insight and Recent Trends.Biomolecules · 2022Review
- Cyclophilin A binds to AKT1 and facilitates the tumorigenicity of Epstein-Barr virus by mediating the activation of AKT/mTOR/NF-κB positive feedback loop.Virologica Sinica · 2022Article
- Potential Application of Leelamine as a Novel Regulator of Chemokine-Induced Epithelial-to-Mesenchymal Transition in Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Emerging role of exosomes in cancer progression and tumor microenvironment remodeling.Journal of hematology & oncology · 2022Review
- δ-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Ptenp-/- Mice.Cancer prevention research (Philadelphia, Pa.) · 2022Article
- Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.Journal of experimental & clinical cancer research : CR · 2022Review
- Ampelopsin targets in cellular processes of cancer: Recent trends and advances.Toxicology reports · 2022Review
25 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
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis is one of the key hallmarks of cancer. In this study, we investigated whether γ-tocotrienol can abrogate angiogenesis-mediated tumor growth in hepatocellular carcinoma (HCC) and if so, through what molecular mechanisms. We observed that γ-tocotrienol inhibited vascular endothelial growth factor (VEGF)-induced migration, invasion, tube formation and viability of HUVECs in vitro. Moreover, γ-tocotrienol reduced the number of capillary sprouts from matrigel embedded rat thoracic aortic ring in a dose-dependent manner. Also, in chick chorioallantoic membrane assay, γ-tocotrienol significantly reduced the blood vessels formation. We further noticed that γ-tocotrienol blocked angiogenesis in an in vivo matrigel plug assay. Furthermore, γ-tocotrienol inhibited VEGF-induced autophosphorylation of VEGFR2 in HUVECs and also suppressed the constitutive activation of AKT/mammalian target of rapamycin (mTOR) signal transduction cascades in HUVECs as well as in HCC cells. Interestingly, γ-tocotrienol was also found to significantly reduce the tumor growth in an orthotopic HCC mouse model and inhibit tumor-induced angiogenesis in HCC patient xenografts through the suppression of various biomarkers of proliferation and angiogenesis. Taken together, our findings strongly suggest that γ-tocotrienol might be a promising anti-angiogenic drug with significant antitumor activity in HCC.
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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.