Gamma Tocotrienol and Pancreatic Cancer

Byron's Comments:

This study adds to the significant body of data indicating tocotrienols are helpful in the war on cancer.

Study Title:

{gamma}-Tocotrienol Inhibits Pancreatic Tumors and Sensitizes Them to Gemcitabine Treatment by Modulating the Inflammatory Microenvironment.

Study Abstract:

Pancreatic cancers generally respond poorly to chemotherapy, prompting a need to identify agents that could sensitize tumors to treatment. In this study, we investigated the response of human pancreatic cells to γ-tocotrienol (γ-T3), a novel, unsaturated form of vitamin E found in palm oil and rice bran oil, to determine whether it could potentiate the effects of gemcitabine, a standard of care in clinical treatment of pancreatic cancer. γ-T3 inhibited the in vitro proliferation of pancreatic cancer cell lines with variable p53 status and potentiated gemcitabine-induced apoptosis. These effects correlated with an inhibition of NF-κB activation by γ-T3 and a suppression of key cellular regulators including cyclin D1, c-Myc, cyclooxygenase-2 (COX-2), Bcl-2, cellular inhibitor of apoptosis protein, survivin, vascular endothelial growth factor (VEGF), ICAM-1, and CXCR4. In an orthotopic nude mouse model of human pancreatic cancer, p.o. administration of γ-T3 inhibited tumor growth and enhanced the antitumor properties of gemcitabine. Immunohistochemical analysis indicated a correlation between tumor growth inhibition and reduced expression of Ki-67, COX-2, matrix metalloproteinase-9 (MMP-9), NF-κB p65, and VEGF in the tissue. Combination treatment also downregulated NF-κB activity along with the NF-κB-regulated gene products, such as cyclin D1, c-Myc, VEGF, MMP-9, and CXCR4. Consistent with an enhancement of tumor apoptosis, caspase activation was observed in tumor tissues. Overall, our findings suggest that γ-T3 can inhibit the growth of human pancreatic tumors and sensitize them to gemcitabine by suppressing NF-κB-mediated inflammatory pathways linked to tumorigenesis. Cancer Res; 70(21); 8695-705. ©2010 AACR.

Study Information:

Kunnumakkara AB, Sung B, Ravindran J, Diagaradjane P, Deorukhkar A, Dey S, Koca C, Yadav VR, Tong Z, Gelovani JG, Guha S, Krishnan S, Aggarwal BB. {gamma}-Tocotrienol Inhibits Pancreatic Tumors and Sensitizes Them to Gemcitabine Treatment by Modulating the Inflammatory Microenvironment. Cancer Res. 2010 October 
: Departments of Experimental Therapeutics, Radiation Oncology, Experimental Diagnostic Imaging, and Gastrointestinal Medicine and Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, Texas.




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