ArticleCarcinogenesis2013
Prolonged survival and delayed progression of pancreatic intraepithelial neoplasia in LSL-KrasG12D/+;Pdx-1-Cre mice by vitamin E δ-tocotrienol.
Article in Carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Unlocking the Potential of Bioactive Compounds in Pancreatic Cancer Therapy: A Promising Frontier.Biomolecules · 2025Review
- Vitamin E in the management of pancreatic cancer: A scoping review.World journal of gastrointestinal oncology · 2023Article
- Clinical and Molecular Attributes and Evaluation of Pancreatic Cystic Neoplasm.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species.Oncogenesis · 2022Article
- Farnesyl dimethyl chromanol targets colon cancer stem cells and prevents colorectal cancer metastasis.Scientific reports · 2021Article
- Tocotrienols Modulate a Life or Death Decision in Cancers.International journal of molecular sciences · 2019Review
- Vitamin E δ-tocotrienol sensitizes human pancreatic cancer cells to TRAIL-induced apoptosis through proteasome-mediated down-regulation of c-FLIPCancer cell international · 2019Article
- Natural Forms of Vitamin E as Effective Agents for Cancer Prevention and Therapy.Advances in nutrition (Bethesda, Md.) · 2017Review
- δ-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem-like cells and prevents pancreatic cancer metastasis.Oncotarget · 2017Article
- Oxidative Stress: A New Target for Pancreatic Cancer Prognosis and Treatment.Journal of clinical medicine · 2017Review
- Berries and other natural products in the pancreatic cancer chemoprevention in human clinical trials.Journal of berry research · 2017Article
- Targeting reactive oxygen species in development and progression of pancreatic cancer.Expert review of anticancer therapy · 2017Review
- The triterpenoid CDDO-imidazolide reduces immune cell infiltration and cytokine secretion in the KrasG12D;Pdx1-Cre (KC) mouse model of pancreatic cancer.Carcinogenesis · 2016Article
- Pharmacokinetics and safety of vitamin E δ-tocotrienol after single and multiple doses in healthy subjects with measurement of vitamin E metabolites.Cancer chemotherapy and pharmacology · 2016Article
- A Phase I Safety, Pharmacokinetic, and Pharmacodynamic Presurgical Trial of Vitamin E δ-tocotrienol in Patients with Pancreatic Ductal Neoplasia.EBioMedicine · 2015Article
- Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications.Advances in nutrition (Bethesda, Md.) · 2015Review
- GEMMs as preclinical models for testing pancreatic cancer therapies.Disease models & mechanisms · 2015Review
- Molecular Targeted Intervention for Pancreatic Cancer.Cancers · 2015Review
- EGR-1/Bax pathway plays a role in vitamin E δ-tocotrienol-induced apoptosis in pancreatic cancer cells.The Journal of nutritional biochemistry · 2015Article
- miR-429 mediates δ-tocotrienol-induced apoptosis in triple-negative breast cancer cells by targeting XIAP.International journal of clinical and experimental medicine · 2015Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The highly lethal nature of pancreatic cancer and the increasing recognition of high-risk individuals have made research into chemoprevention a high priority. Here, we tested the chemopreventive activity of δ-tocotrienol, a bioactive vitamin E derivative extracted from palm fruit, in the LSL-Kras(G12D/+);Pdx-1-Cre pancreatic cancer mouse model. At 10 weeks of age, mice (n = 92) were randomly allocated to three groups: (i) no treatment; (ii) vehicle and (iii) δ-tocotrienol (200mg/kg × 2/day, PO). Treatment was continued for 12 months. Mice treated with δ-tocotrienol showed increased median survival from the onset of treatment (11.1 months) compared with vehicle-treated mice (9.7 months) and non-treated mice (8.5 months; P < 0.025). Importantly, none of the mice treated with δ-tocotrienol harbored invasive cancer compared with 10% and 8% in vehicle-treated and non-treated mice, respectively. Furthermore, δ-tocotrienol treatment also resulted in significant suppression of mouse pancreatic intraepithelial neoplasm (mPanIN) progression compared with vehicle-treated and non-treated mice: mPanIN-1: 47-50% (P < 0.09), mPanIN-2: 6-11% (P < 0.001), mPanIN-3: 3-15% (P < 0.001) and invasive cancer: 0-10% (P < 0.001). δ-Tocotrienol treatment inhibited mutant Kras-driven pathways such as MEK/ERK, PI3K/AKT and NF-kB/p65, as well as Bcl-xL and induced p27. δ-Tocotrienol also induced biomarkers of apoptosis such as Bax and activated caspase 3 along with an increase in plasma levels of CK18. In summary, δ-tocotrienol's ability to interfere with oncogenic Kras pathways coupled with the observed increase in median survival and significant delay in PanIN progression highlights the chemopreventative potential of δ-tocotrienol and warrants further investigation of this micronutrient in individuals at high risk for pancreatic cancer.
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Registered trials
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