| First Author | Husain K | Year | 2013 |
| Journal | Carcinogenesis | Volume | 34 |
| Issue | 4 | Pages | 858-63 |
| PubMed ID | 23302291 | Mgi Jnum | J:196905 |
| Mgi Id | MGI:5490182 | Doi | 10.1093/carcin/bgt002 |
| Citation | Husain K, et al. (2013) Prolonged survival and delayed progression of pancreatic intraepithelial neoplasia in LSL-KrasG12D/+;Pdx-1-Cre mice by vitamin E delta-tocotrienol. Carcinogenesis 34(4):858-63 |
| abstractText | 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 delta-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) delta-tocotrienol (200mg/kg x 2/day, PO). Treatment was continued for 12 months. Mice treated with delta-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 delta-tocotrienol harbored invasive cancer compared with 10% and 8% in vehicle-treated and non-treated mice, respectively. Furthermore, delta-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). delta-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. delta-Tocotrienol also induced biomarkers of apoptosis such as Bax and activated caspase 3 along with an increase in plasma levels of CK18. In summary, delta-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 delta-tocotrienol and warrants further investigation of this micronutrient in individuals at high risk for pancreatic cancer. |
