ArticlePloS one2015
δ-tocotrienol induces human bladder cancer cell growth arrest, apoptosis and chemosensitization through inhibition of STAT3 pathway.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of Vitamin and Antioxidant Supplements in Prevention of Bladder Cancer: a Meta-Analysis of Randomized Controlled Trials.Journal of Korean medical science · 2017Pooled it
- The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.Antioxidants (Basel, Switzerland) · 2026Review
- Evidence for a Tumor-Suppressive Role of SHP-1 in EMT Regulation in Bladder Cancer Cells.Cancers · 2026Article
- Antioxidant Food Supplementation in Cancer: Lessons from Clinical Trials and Insights from Preclinical Studies.Antioxidants (Basel, Switzerland) · 2025Review
- Programmed Cell Death in Cancer.MedComm · 2025Review
- Phytochemicals as Chemo-Preventive and Therapeutic Agents Against Bladder Cancer: A Comprehensive Review.Diseases (Basel, Switzerland) · 2025Review
- Revisiting the therapeutic potential of tocotrienol.BioFactors (Oxford, England) · 2022Review
- Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols.Molecular carcinogenesis · 2020Review
- Vitamin E and cancer: an update on the emerging role of γ and δ tocotrienols.European journal of nutrition · 2020Review
- Molecular Mechanisms of Action of Tocotrienols in Cancer: Recent Trends and Advancements.International journal of molecular sciences · 2019Review
- Tocotrienols Modulate a Life or Death Decision in Cancers.International journal of molecular sciences · 2019Review
- Combination of gemcitabine and erlotinib inhibits recurrent pancreatic cancer growth in mice via the JAK-STAT pathway.Oncology reports · 2018Article
- Challenges and Opportunities of Nanotechnology as Delivery Platform for Tocotrienols in Cancer Therapy.Frontiers in pharmacology · 2018Review
- δ-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem-like cells and prevents pancreatic cancer metastasis.Oncotarget · 2017Article
- Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas.International journal of molecular sciences · 2016Article
- miR-429 mediates δ-tocotrienol-induced apoptosis in triple-negative breast cancer cells by targeting XIAP.International journal of clinical and experimental medicine · 2015Article
- Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin.PloS one · 2015Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vitamin E intake has been implicated in reduction of bladder cancer risk. However, the mechanisms remain elusive. Here we reported that δ-tocotrienol (δ-T3), one of vitamin E isomers, possessed the most potent cytotoxic capacity against human bladder cancer cells, compared with other Vitamin E isomers. δ-T3 inhibited cancer cell proliferation and colonogenicity through induction of G1 phase arrest and apoptosis. Western blotting assay revealed that δ-T3 increased the expression levels of cell cycle inhibitors (p21, p27), pro-apoptotic protein (Bax) and suppressed expression levels of cell cycle protein (Cyclin D1), anti-apoptotic proteins (Bcl-2, Bcl-xL and Mcl-1), resulting in the Caspase-3 activation and cleavage of PARP. Moreover, the δ-T3 treatment inhibited ETK phosphorylation level and induced SHP-1 expression, which was correlated with downregulation of STAT3 activation. In line with this, δ-T3 reduced the STAT3 protein level in nuclear fraction, as well as its transcription activity. Knockdown of SHP-1 partially reversed δ-T3-induced cell growth arrest. Importantly, low dose of δ-T3 sensitized Gemcitabine-induced cytotoxic effects on human bladder cancer cells. Overall, our findings demonstrated, for the first time, the cytotoxic effects of δ-T3 on bladder cancer cells and suggest that δ-T3 might be a promising chemosensitization reagent for Gemcitabine in bladder cancer treatment.
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