Abstract
The tumor-suppressive activity of tocotrienols, vitamin E molecules with an unsaturated isoprenoid side chain, has been extensively reviewed in the previous edition of this book (Mo and Elson 2008). Tocotrienols at physiologically attainable concentrations suppress the proliferation of tumor cells derived from breast, liver, prostate, skin, colon, blood, lung, lymph gland, cervix, and nerve. Tocotrienol-mediated growth suppression is attributed to cell cycle arrest, mostly at the G1 phase of cell cycle, and apoptosis. Signaling pathways associated with promoting cell cycle progression, growth, and survival, including mitogen-activated protein kinases (MAPK), Ras, RhoA, Raf/MAPK kinase (MEK)/extracellular signal-regulated kinases (ERK), c-Jun, c-myc, cyclin D/cdk4, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), Akt, IκB kinase (IKK), IκB, nuclear factor κB (NFκB), c-Jun N-terminal kinase (JNK), Bcl-2, Bcl-xL, COX-2, matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), FLIP, and telomerase, are suppressed by tocotrienols. On the other hand, signaling activities supporting growth arrest and apoptosis, including p21cip1WAF1, transforming growth factor-β (TGF-β), p53, Fas, Bax, Apaf-1, caspases, and Bid fragmentation, are activated by tocotrienols. Animal models with chemically initiated carcinogenesis and implanted tumors confirmed the in vitro tumor-suppressive activity of tocotrienols. Differing from statins, the nondiscriminant competitive inhibitors of 3-hydroxy-3-methyglutaryl coenzyme A (HMG CoA) reductase, tocotrienols are downregulators of the activity of HMG CoA reductase. Dysregulation of HMG CoA reductase in tumors offers a unique target for tumor-specific intervention. Recent literature continues to support the potential of tocotrienols as tumor-targeted agents in cancer chemoprevention and/or therapy.
Original language | English (US) |
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Title of host publication | Tocotrienols |
Subtitle of host publication | Vitamin E beyond Tocopherols, Second Edition |
Publisher | CRC Press |
Pages | 135-150 |
Number of pages | 16 |
ISBN (Electronic) | 9781439884430 |
ISBN (Print) | 9781439884416 |
DOIs | |
State | Published - Jan 1 2012 |
ASJC Scopus subject areas
- General Medicine
- General Biochemistry, Genetics and Molecular Biology
- General Engineering
- General Agricultural and Biological Sciences