Cancer-preventive activities of tocopherols and tocotrienols.

Publisher: Irl Press At Oxford University Press Country of Publication: England NLM ID: 8008055 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2180 (Electronic) Linking ISSN: 01433334 NLM ISO Abbreviation: Carcinogenesis Subsets: MEDLINE

Publication: Oxford : Irl Press At Oxford University Press
Original Publication: [New York, IRL Press]

Anticarcinogenic Agents/*pharmacology ; Tocopherols/*pharmacology ; Tocotrienols/*pharmacology; Animals ; Antioxidants/pharmacology ; Apoptosis/drug effects ; Case-Control Studies ; Cyclooxygenase 2 Inhibitors/pharmacology ; Female ; Humans ; Male ; Neoplasms/prevention & control ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; Receptors, Cytoplasmic and Nuclear/drug effects ; Tocopherols/metabolism

The cancer-preventive activity of vitamin E has been studied. Whereas some epidemiological studies have suggested a protective effect of vitamin E against cancer formation, many large-scale intervention studies with alpha-tocopherol (usually large doses) have not demonstrated a cancer-preventive effect. Studies on alpha-tocopherol in animal models also have not demonstrated robust cancer prevention effects. One possible explanation for the lack of demonstrable cancer-preventive effects is that high doses of alpha-tocopherol decrease the blood and tissue levels of delta-tocopherols. It has been suggested that gamma-tocopherol, due to its strong anti-inflammatory and other activities, may be the more effective form of vitamin E in cancer prevention. Our recent results have demonstrated that a gamma-tocopherol-rich mixture of tocopherols inhibits colon, prostate, mammary and lung tumorigenesis in animal models, suggesting that this mixture may have a high potential for applications in the prevention of human cancer. In this review, we discuss biochemical properties of tocopherols, results of possible cancer-preventive effects in humans and animal models and possible mechanisms involved in the inhibition of carcinogenesis. Based on this information, we propose that a gamma-tocopherol-rich mixture of tocopherols is a very promising cancer-preventive agent and warrants extensive future research.

198

N Engl J Med. 1993 Jul 22;329(4):234-40. (PMID: 8292129)
Free Radic Biol Med. 2002 Dec 1;33(11):1534-42. (PMID: 12446211)
Am J Epidemiol. 1988 Jan;127(1):28-41. (PMID: 3276161)
Am J Epidemiol. 1996 Jul 15;144(2):165-74. (PMID: 8678048)
J Lipid Res. 2007 May;48(5):1090-8. (PMID: 17284776)
Biochem Biophys Res Commun. 2006 Apr 21;342(4):1329-33. (PMID: 16516856)
Free Radic Biol Med. 2008 Mar 15;44(6):1203-8. (PMID: 18191645)
FASEB J. 2002 Dec;16(14):1952-4. (PMID: 12368234)
Arch Biochem Biophys. 1999 Mar 15;363(2):333-40. (PMID: 10068456)
Nutrition. 2008 Jan;24(1):1-10. (PMID: 17884341)
J Natl Cancer Inst. 1999 Mar 17;91(6):547-56. (PMID: 10088626)
Cell Prolif. 2006 Dec;39(6):563-74. (PMID: 17109639)
Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17825-30. (PMID: 15596715)
Basic Clin Pharmacol Toxicol. 2008 Jul;103(1):55-60. (PMID: 18598299)
Am J Epidemiol. 1997 Aug 1;146(3):231-43. (PMID: 9247007)
Cancer Res. 2004 Aug 15;64(16):5891-6. (PMID: 15313934)
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1253-9. (PMID: 17548693)
Clin Cancer Res. 2009 Jun 15;15(12):4242-9. (PMID: 19509159)
Br J Cancer. 1999 Jan;79(1):23-9. (PMID: 10408688)
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3217-22. (PMID: 9096373)
N Engl J Med. 1995 May 4;332(18):1198-203. (PMID: 7700313)
Cancer Epidemiol Biomarkers Prev. 1999 Oct;8(10):893-9. (PMID: 10548318)
Nutr Cancer. 1998;30(3):201-6. (PMID: 9631491)
Cancer Lett. 2005 Nov 18;229(2):181-91. (PMID: 16098658)
Breast J. 2000 Jan;6(1):14-19. (PMID: 11348329)
Front Biosci. 2007 Jan 01;12:2013-9. (PMID: 17127439)
Chem Res Toxicol. 1997 Apr;10(4):401-7. (PMID: 9114976)
Lipids. 1995 Dec;30(12):1139-43. (PMID: 8614304)
Nutr Rev. 1997 Oct;55(10):376-8. (PMID: 9354084)
J Lipid Res. 2007 May;48(5):1221-30. (PMID: 17299205)
Cancer Epidemiol Biomarkers Prev. 2001 Jan;10(1):65-8. (PMID: 11205491)
J Natl Cancer Inst. 1998 Mar 18;90(6):440-6. (PMID: 9521168)
Mol Aspects Med. 2007 Oct-Dec;28(5-6):668-91. (PMID: 17316780)
Cancer Epidemiol Biomarkers Prev. 1997 Oct;6(10):769-74. (PMID: 9332757)
Ann N Y Acad Sci. 2004 Dec;1031:405-11. (PMID: 15753182)
J Natl Cancer Inst. 2006 Feb 15;98(4):245-54. (PMID: 16478743)
Int J Cancer. 2008 Aug 15;123(4):739-52. (PMID: 18512238)
J Nutr. 2003 Oct;133(10):3137-40. (PMID: 14519797)
Int J Cancer. 2001 Feb 15;91(4):563-7. (PMID: 11251982)
Biochem Pharmacol. 2008 Aug 1;76(3):330-9. (PMID: 18599020)
Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H361-7. (PMID: 15708953)
Cancer Causes Control. 2000 Mar;11(3):197-205. (PMID: 10782653)
Cancer Epidemiol Biomarkers Prev. 1999 Oct;8(10):887-92. (PMID: 10548317)
Cancer Res. 1980 Apr;40(4):1329-31. (PMID: 7357560)
Cancer Res. 1999 Mar 15;59(6):1225-30. (PMID: 10096552)
JAMA. 2009 Jan 7;301(1):52-62. (PMID: 19066368)
Cancer Causes Control. 2002 Aug;13(6):573-82. (PMID: 12195647)
Am J Clin Nutr. 2006 Aug;84(2):375-83. (PMID: 16895886)
Cancer Epidemiol Biomarkers Prev. 2002 May;11(5):451-7. (PMID: 12010859)
Eur J Cancer. 1997 Jan;33(1):101-7. (PMID: 9071908)
J Lipid Res. 1999 Apr;40(4):665-71. (PMID: 10191290)
Arch Biochem Biophys. 2006 Mar 15;447(2):97-106. (PMID: 16530159)
Br J Cancer. 1997;75(1):149-55. (PMID: 9000614)
Ann Nutr Metab. 2004;48(3):169-88. (PMID: 15256801)
Int J Cancer. 2005 Jul 10;115(5):839-46. (PMID: 15723336)
Br J Cancer. 1992 Oct;66(4):673-9. (PMID: 1419605)
Cancer Epidemiol Biomarkers Prev. 1997 Nov;6(11):907-16. (PMID: 9367064)
J Biol Chem. 2007 Jan 5;282(1):809-20. (PMID: 17114179)
Biochem Pharmacol. 2003 Jan 15;65(2):269-73. (PMID: 12504802)
J Nutr. 1997 May;127(5):668-74. (PMID: 9164984)
J Nutr. 2008 Nov;138(11):2136-42. (PMID: 18936210)
Eur J Clin Nutr. 2002 Jul;56(7):615-21. (PMID: 12080400)
J Nutr Biochem. 2009 Aug;20(8):607-13. (PMID: 18824342)
Eur Urol. 1999;35(5-6):464-7. (PMID: 10325506)
BMC Cancer. 2006 Jan 17;6:13. (PMID: 16417629)
Am J Clin Nutr. 2001 Dec;74(6):714-22. (PMID: 11722951)
Eur J Biochem. 1997 Jun 15;246(3):745-9. (PMID: 9219534)
Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1298-304. (PMID: 12433706)
Am J Clin Nutr. 1991 Jan;53(1 Suppl):283S-286S. (PMID: 1985399)
J Natl Cancer Inst. 2000 Dec 20;92(24):2018-23. (PMID: 11121464)
J Natl Cancer Inst. 1996 Mar 20;88(6):340-8. (PMID: 8609642)
Breast. 2005 Jun;14(3):209-23. (PMID: 15927830)
J Natl Cancer Inst. 1986 Jun;76(6):1157-62. (PMID: 3458951)
Annu Rev Nutr. 2007;27:347-62. (PMID: 17439363)
Br J Nutr. 2008 Jun;99(6):1247-54. (PMID: 18081943)
J Natl Cancer Inst. 1996 Nov 6;88(21):1560-70. (PMID: 8901854)
Chem Biol Interact. 1993 Mar;86(3):199-211. (PMID: 8485784)
J Urol. 1999 May;161(5):1651-4. (PMID: 10210433)
Nutr Cancer. 1997;28(3):258-63. (PMID: 9343834)
Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20464-9. (PMID: 19074288)
Eur J Cancer Prev. 2004 Dec;13(6):515-20. (PMID: 15548946)
J Nutr. 1997 Mar;127(3):544S-548S. (PMID: 9082043)
J Natl Cancer Inst. 1998 Mar 4;90(5):389-94. (PMID: 9498489)
Am J Clin Nutr. 1991 Apr;53(4 Suppl):1076S-1081S. (PMID: 1672785)
Gastroenterology. 2007 Jun;132(7):2518-32. (PMID: 17570223)
Int J Cancer. 1999 Mar 1;80(5):704-8. (PMID: 10048971)
Cancer Causes Control. 2006 Nov;17(9):1193-207. (PMID: 17006725)
J Natl Cancer Inst. 1986 May;76(5):939-42. (PMID: 3457978)
Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3604-9. (PMID: 16505371)
Circulation. 2000 Jul 4;102(1):82-7. (PMID: 10880419)
Food Chem Toxicol. 1999 Sep-Oct;37(9-10):985-92. (PMID: 10541455)
Cancer Epidemiol Biomarkers Prev. 1997 Jul;6(7):487-91. (PMID: 9232334)
N Engl J Med. 1986 Nov 13;315(20):1250-4. (PMID: 3773937)
Clin Exp Pharmacol Physiol. 2005 Sep;32(9):761-70. (PMID: 16173934)
Mutat Res. 2004 Jul 13;551(1-2):245-54. (PMID: 15225597)
BMC Cancer. 2003 Oct 01;3:25. (PMID: 14521714)
Int J Cancer. 2008 Sep 1;123(5):1173-80. (PMID: 18546288)
Nutr Cancer. 1999;33(1):26-32. (PMID: 10227040)
Free Radic Res. 2001 Sep;35(3):329-39. (PMID: 11697131)
Br J Cancer. 1999 May;80(3-4):591-7. (PMID: 10408871)
Cell Prolif. 2001 Dec;34(6):347-57. (PMID: 11736999)
Nutr Cancer. 2004;49(1):72-80. (PMID: 15456638)
Free Radic Biol Med. 1995 Sep;19(3):259-69. (PMID: 7557540)
JAMA. 2009 Jan 7;301(1):39-51. (PMID: 19066370)
Eur J Nutr. 2007 Feb;46(1):34-43. (PMID: 17180484)
Cancer Res. 1993 Sep 15;53(18):4230-7. (PMID: 8364919)
JAMA. 2005 Jul 6;294(1):56-65. (PMID: 15998891)
Cell Cycle. 2004 Feb;3(2):205-11. (PMID: 14712090)
Int J Cancer. 2009 Apr 1;124(7):1693-9. (PMID: 19115203)
Ann N Y Acad Sci. 2004 Dec;1031:399-400. (PMID: 15753180)
Biochem Cell Biol. 2005 Feb;83(1):86-95. (PMID: 15746970)
J Nutr. 2006 May;136(5):1287-93. (PMID: 16614418)
Cancer Res. 1990 Nov 1;50(21):6836-40. (PMID: 2208150)
Free Radic Res. 2008 Jul;42(7):674-87. (PMID: 18654882)
J Clin Epidemiol. 1993 Sep;46(9):1009-17. (PMID: 8263573)
Mol Aspects Med. 2007 Oct-Dec;28(5-6):692-728. (PMID: 17507086)
Int J Cancer. 1996 Apr 10;66(2):145-50. (PMID: 8603802)
Eur J Cancer. 2001 May;37(8):948-65. (PMID: 11334719)
Biochem Biophys Res Commun. 2006 Jul 28;346(2):447-53. (PMID: 16762318)
J Natl Cancer Inst. 2003 Sep 17;95(18):1414-6. (PMID: 13130117)
Clin Biochem. 2001 Feb;34(1):71-6. (PMID: 11239519)
Nutr Cancer. 2002;43(1):111-8. (PMID: 12467142)
Exp Biol Med (Maywood). 2004 Sep;229(8):745-55. (PMID: 15337828)
Semin Urol Oncol. 1999 May;17(2):85-90. (PMID: 10332921)
Cancer Causes Control. 1995 Sep;6(5):407-15. (PMID: 8547538)
Life Sci. 2009 May 8;84(19-20):650-6. (PMID: 19232361)
FASEB J. 2003 May;17(8):816-22. (PMID: 12724340)
Exp Biol Med (Maywood). 2005 Apr;230(4):235-41. (PMID: 15792944)
Am J Epidemiol. 1992 Dec 1;136(11):1327-37. (PMID: 1336931)
Am J Epidemiol. 2003 Feb 15;157(4):335-44. (PMID: 12578804)
Cancer. 1988 Nov 1;62(9):2021-6. (PMID: 3167814)
Cancer Epidemiol Biomarkers Prev. 2003 Jun;12(6):518-26. (PMID: 12814997)
Free Radic Biol Med. 2005 Oct 1;39(7):970-6. (PMID: 16140216)
J Lipid Res. 1984 Jan;25(1):40-8. (PMID: 6707520)
Cancer. 1997 Sep 1;80(5):858-64. (PMID: 9307184)
J Nutr. 2003 Feb;133(2):528-32. (PMID: 12566495)
Nutr Cancer. 1996;26(1):99-109. (PMID: 8844726)
Mol Nutr Food Res. 2009 Aug;53(8):1030-5. (PMID: 19557822)
Am J Epidemiol. 2005 Jan 15;161(2):153-60. (PMID: 15632265)
JAMA. 2003 Jul 23;290(4):476-85. (PMID: 12876090)
J Nutr Biochem. 2006 Oct;17(10):672-6. (PMID: 16517139)
Cancer Causes Control. 1999 Jun;10(3):219-26. (PMID: 10454067)
Nutr Cancer. 1999;35(2):111-9. (PMID: 10693163)
J Nutr Biochem. 2009 Apr;20(4):276-84. (PMID: 18602811)
Cancer Causes Control. 1993 Jan;4(1):29-37. (PMID: 8381678)
Cancer Prev Res (Phila). 2009 Feb;2(2):143-52. (PMID: 19155443)
Nutr Cancer. 2004;48(1):95-105. (PMID: 15203383)
J Natl Cancer Inst. 1992 Mar 18;84(6):430-5. (PMID: 1531683)
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1128-35. (PMID: 17548674)
J Biol Chem. 2008 Jun 27;283(26):17797-804. (PMID: 18458085)
J Appl Physiol (1985). 1994 Dec;77(6):2912-7. (PMID: 7896640)
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1771-5. (PMID: 8446589)
Biochem Biophys Res Commun. 2000 Mar 16;269(2):580-3. (PMID: 10708597)
Cancer Causes Control. 1992 Nov;3(6):503-12. (PMID: 1420852)
Am J Clin Nutr. 1991 Apr;53(4 Suppl):1068S-1070S. (PMID: 1845366)
J Lipid Res. 2002 Nov;43(11):1978-85. (PMID: 12401897)
Biol Pharm Bull. 2007 Jan;30(1):200-4. (PMID: 17202688)
Int J Food Sci Nutr. 2000;51 Suppl:S95-103. (PMID: 11271861)
Breast J. 2000 Nov;6(6):388-395. (PMID: 11348397)
Free Radic Biol Med. 2004 Jan 1;36(1):1-15. (PMID: 14732286)
J Clin Epidemiol. 1999 May;52(5):429-39. (PMID: 10360338)
Cancer Lett. 1991 Jul 4;58(3):241-6. (PMID: 1855198)
Prostate. 1999 Feb 15;38(3):189-98. (PMID: 10068343)
Jpn J Cancer Res. 1999 Apr;90(4):399-405. (PMID: 10363577)
Cancer Causes Control. 1995 Mar;6(2):145-54. (PMID: 7749054)
J Nutr. 2002 Oct;132(10):3113-8. (PMID: 12368403)
Clin Cancer Res. 2002 Jun;8(6):1772-8. (PMID: 12060616)
Biochem Pharmacol. 1994 Mar 29;47(7):1173-7. (PMID: 8161346)
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11494-9. (PMID: 11005841)
Nutr Cancer. 2007;59(1):76-81. (PMID: 17927505)
Biochem Biophys Res Commun. 2008 Jan 25;365(4):875-81. (PMID: 18042466)
Nutr Cancer. 2006;56(1):82-5. (PMID: 17176221)
Int J Cancer. 1994 May 15;57(4):529-31. (PMID: 8181855)
J Neurol Sci. 2006 Apr 15;243(1-2):5-12. (PMID: 16442562)
Cancer Lett. 1987 Apr;35(1):71-7. (PMID: 3567889)
J Nutr Biochem. 2010 Mar;21(3):206-13. (PMID: 19195866)
Biochem J. 1998 Aug 15;334 ( Pt 1):243-9. (PMID: 9693126)
Br J Cancer. 2008 Dec 2;99(11):1832-41. (PMID: 19002171)
J Clin Invest. 1992 Dec;90(6):2502-7. (PMID: 1469101)
Cancer Res. 1998 Feb 15;58(4):661-6. (PMID: 9485018)
J Natl Cancer Inst. 1983 Jun;70(6):1107-11. (PMID: 6574281)
Cancer Epidemiol Biomarkers Prev. 2004 Mar;13(3):378-82. (PMID: 15006912)
Biochem Biophys Res Commun. 2006 Sep 15;348(1):170-5. (PMID: 16875674)
Crit Rev Oncol Hematol. 2003 Sep;47(3):249-59. (PMID: 12962899)
Nutr Cancer. 1998;31(3):168-77. (PMID: 9795968)
J Biol Chem. 2002 Jul 12;277(28):25290-6. (PMID: 11997390)
Int J Cancer. 1996 Dec 11;68(6):716-22. (PMID: 8980172)
J Nutr. 2005 Feb;135(2):227-32. (PMID: 15671218)
Cancer Lett. 1997 Mar 19;114(1-2):251-3. (PMID: 9103304)
Cancer Causes Control. 2000 Feb;11(2):129-35. (PMID: 10710196)
Environ Mol Mutagen. 2002;39(2-3):271-8. (PMID: 11921198)
Biochim Biophys Acta. 2008 Sep;1782(9):498-503. (PMID: 18555028)
Cancer Causes Control. 1998 Jan;9(1):89-97. (PMID: 9486468)
J Lipid Res. 2005 Oct;46(10):2072-82. (PMID: 16024914)

CA120915 United States CA NCI NIH HHS; P30 ES005022 United States ES NIEHS NIH HHS; CA133021 United States CA NCI NIH HHS; R01 CA122474 United States CA NCI NIH HHS; CA122474 United States CA NCI NIH HHS; R01 CA122474-04 United States CA NCI NIH HHS; CA108455-05 United States CA NCI NIH HHS

0 (Anticarcinogenic Agents)
0 (Antioxidants)
0 (Cyclooxygenase 2 Inhibitors)
0 (Reactive Nitrogen Species)
0 (Reactive Oxygen Species)
0 (Receptors, Cytoplasmic and Nuclear)
0 (Tocotrienols)
R0ZB2556P8 (Tocopherols)

Date Created: 20090915 Date Completed: 20100416 Latest Revision: 20240516

20250114

PMC2860705

10.1093/carcin/bgp205

19748925