Inhibitory effect of tocotrienol on eukaryotic DNA polymerase {lambda} and angiogenesis
- Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan) and High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan)
- Food and Biodynamic Chemistry Laboratory, Graduate School of Life Science and Agriculture, Tohoku University, Sendai 981-8555 (Japan)
- Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan)
- Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510 (Japan)
Tocotrienols, vitamin E compounds that have an unsaturated side chain with three double bonds, selectively inhibited the activity of mammalian DNA polymerase {lambda} (pol {lambda}) in vitro. These compounds did not influence the activities of replicative pols such as {alpha}, {delta}, and {epsilon}, or even the activity of pol {beta} which is thought to have a very similar three-dimensional structure to the pol {beta}-like region of pol {lambda}. Since {delta}-tocotrienol had the strongest inhibitory effect among the four ({alpha}- to {delta}-) tocotrienols, the isomer's structure might be an important factor in the inhibition of pol {lambda}. The inhibitory effect of {delta}-tocotrienol on both intact pol {lambda} (residues 1-575) and a truncated pol {lambda} lacking the N-terminal BRCA1 C-terminus (BRCT) domain (residues 133-575, del-1 pol {lambda}) was dose-dependent, with 50% inhibition observed at a concentration of 18.4 and 90.1 {mu}M, respectively. However, del-2 pol {lambda} (residues 245-575) containing the C-terminal pol {beta}-like region was unaffected. Tocotrienols also inhibited the proliferation of and formation of tubes by bovine aortic endothelial cells, with {delta}-tocotrienol having the greatest effect. These results indicated that tocotrienols targeted both pol {lambda} and angiogenesis as anti-cancer agents. The relationship between the inhibition of pol {lambda} and anti-angiogenesis by {delta}-tocotrienol was discussed.
- OSTI ID:
- 20798757
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 339, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2005.11.085; PII: S0006-291X(05)02636-7; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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