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Antioxidants in Dietary Oils: Their Potential Role in Breast Cancer Prevention

Sylvester, Paul W., and Shah, Sumit, (2002) Antioxidants in Dietary Oils: Their Potential Role in Breast Cancer Prevention. Malaysian Journal of Nutrition, 8 (1). pp. 1-11. ISSN 1394-035X

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University of Louisiana at Monroe, College of Pharmacy


Edible oils contain variable amounts of natural antioxidants such as vitamin E. Antioxidants act not only to prevent lipid peroxidation and free-radical production, but also display potent anticancer activity. The vitamin E family of compounds is divided into two subgroups called tocopherols and tocotrienols, but only tocotrienols display potent anticancer activity at treatment doses that have little or no effect on normal cell growth or viability. Palm oil contains the highest concentrations of natural tocotrienols. Tocotrienols induced apoptosis or programmed cell death in breast cancer cells. Morphological and biochemical characteristics of apoptosis, such as nuclear and cytoplasmic condensation and DNA fragmentation, are mediated by the activation of cysteine proteases called caspases. Apoptosis is triggered by the activation of initiator caspases (caspase-8 or 9) that subsequently activate effector caspases (caspase-3, 6, and 7). Studies were conducted using the highly malignant +SA mouse mammary epithelial cell line to determine if tocotrienol-induced programmed cell death is mediated through the caspase-8 or caspase-9 pathway. Treatment with cytotoxic doses of tocotrienol resulted in a large increase in caspase-8 and caspase-3, but not caspase-9 activity. Combined treatment of tocotrienol with selective caspase-8 or caspase-3 inhibitors completely blocked tocotrieno-linduced apoptosis and activation of caspase-8 and caspase-3, respectively. These findings demonstrate that tocotrienol-induced apoptosis in highly malignant mammary epithelial cells is mediated through caspase-8 activation, and may provide essential information necessary for understanding the potential health benefits of these compounds in preventing and/or reducing the risk of breast cancer in women.

Item Type:Journal
Keywords:Antioxidants, Dietary Oils, Breast Cancer
Subjects:R Medicine, Dentistry, Pharmacy, Nursing
ID Code:2687

1. Anderson LW, Danielson KG & Hosick HL (1981). Metastatic potential of hyperplastic alveolar nodule derived mouse mammary tumor cells following intravenous inoculation. Eur J Cancer Clin Oncol 17: 1001-1008.

2. Ashkenazi A & Dixit VM (1998). Death receptors: signaling and modulation. Science 281: 1305-1308.

3. Bratton SB, MacFarlane M, Cain K & Cohen GM (2000). Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis. Exp Cell Res 256: 27-33.

4. Chatelain E, Boscoboinik DO, Bartoli GM, Kagan VE, Gey FK, Packer L & Azzi A (1993). Inhibition of smooth muscle cell proliferation and protein kinase C activity by tocopherols and tocotrienols. Biochim Biophys Acta 1176: 83-89.

5. Cohen GM (1997). Caspases: the executioners of apoptosis. Biochem J 326: 1-16.

6. Danielson KG, Anderson LW & Hosick HL (1980). Selection and characterization in culture of mammary tumor cells with distinctive growth properties in vivo. Cancer Res 40: 1812-1819.

7. Desagher S, Osen-Sand A, Nichols A, Eskes R, Montessuit S, Lauper S, Maundrell K, Antonsson B & Martinou JC (1999). Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 144: 891-901.

8. Earnshaw WC, Martins LM & Kaufmann SH (1999). Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochern 68: 383-424.

9. Elson CE (1992). Tropical oils: nutritional and scientific issues. Crit Rev Food Sci Nutr 31: 79-102.

10. Fazzio A, Marilley D & Azzi A (1997). The effect of alpha-tocopherol and beta-tocopherol on proliferation, protein kinase C activity and gene expression in different cell lines. Biochem Mol Biol Int 41: 93-101.

11. Green DR & Reed JC (1998). Mitochondria and apoptosis. Science 281: 1309-1312.

12. Heermeier K, Benedict M, Li M, Furth P, Nunez G & Hennighausen L (1996). Bax and Bcl-xs are induced at the onset of apoptosis in involuting mammary epithelial cells. Mech Dev 56: 197-207.

13. Hockenbery D, Nunez G, Milliman C, Schreiber RD & Korsmeyer SJ (1990). Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348: 334-336.

14. Khor HT & Raajeswari R (2001). Red palm oil, vitamin A, and the antioxidant enzymes. In: Micronutrients and Health: Molecular Biological Mechanisms. Nesaretnam K & Packer L (eds.) pp. 299-312. Champaign, IL: AOCS Press.

15. Kimmick GG, Bell PA & Bostick RM (1997). Vitamin E and breast cancer: a review. Nutr Cancer 27: 109-117.

16. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES & Wang X (1997). Cytochrome c and dATP dependent formation of Apaf-1/ caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479-489.

17. Li H, Zhu H, Xu CJ, Yuan J (1998). Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94: 491-501.

18. McIntyre BS, Briski, KP, Tirmenstein MA, Fariss MW, Gapor A & Sylvester PW (2000a). Antiproliferative and apoptotic effects of tocopherols and tocotrienols on normal mouse mammary epithelial cells. Lipids 35: 171-180.

19. McIntyre BS, Briski KP, Gapor A, Sylvester PW (2000b). Antiproliferative and apoptotic effects of tocopherols and tocotrienols on preneoplastic and neoplastic mouse mammary epithelial cells. PSERM 224: 292-301.

20. Muzio M, Stockwell BR, Stennicke HR, Salvesen GS & Dixit VM (1998). An induced proximity model for caspase-8 activation. J Biol Chem 273: 2926-2930.

21. Nass SJ, Li M, Amundadottir LT, Furth PA & Dickson RB (1996). Role for Bcl-xL in the regulation of apoptosis by EGF and TGF beta 1 in c-myc overexpressing mammary epithelial cells. Biochem Biophys Res Commun 227: 248-256.

22. Nicholson DW (1999). Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 6: 1028-1042.

23. Oltvai ZN & Korsmeyer SJ (1994). Checkpoints of dueling dimers foil death wishes [comment]. Cell 79: 189-192.

24. Packer L (1991). Protective role of vitamin E in biological systems. Am J Clin Nutr 53: 1050S-1055S.

25. Sigounas G, Anagnostou A & Steiner M (1997). dl-alpha-tocopherol induces apoptosis in erythroleukemia, prostate, and breast cancer cells. Nutr Cancer 28: 30-35.

26. Slee EA, Adrain C & Martin SJ (1999). Serial killers: ordering caspase activation events in apoptosis. Cell Death Differ 6: 1067-1074.

27. Srinivasula SM, Ahmad M, Fernandes-Alnemri T & Alnemri ES (1998). Autoactivation of procaspase-9 by Apaf1-mediated oligomerization. Mol Cell 1:949-957.

28. Stauble B, Boscoboinik D, Tasinato A & Azzi A (1994). Modulation of activator protein-i (AP-1) transcription factor and protein kinase C by hydrogen peroxide and D-alpha-tocopherol in vascular smooth muscle cells. Eur J Biochem 226: 393-402.

29. Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR & Cohen GM (1999). Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem 274: 5053-5060.

30. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM & Kroemer G (1999). Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441-446.

31. Sylvester PW, Birkenfeld HP, Hosick HL & Briski KP (1994). Fatty acid modulation of epidermal growth factor-induced mouse mammary epithelial cell proliferation in vitro. Exp Cell Res 214: 145-153.

32. Sylvester PW, McIntyre BS, Gapor A & Briski KP (2001). Vitamin E inhibition of normal mammary epithelial cell growth is associated with a reduction in protein kinase Ca activation. Cell Prolif 34: 347-357.

33. Turley JM, Ruscetti FW, Kim SJ, Fu T, Gou FV & Birchenall-Roberts MC (1997). Vitamin E succinate inhibits proliferation of BT-20 human breast cancer cells: increased binding of cyclin A negatively regulates E2F transactivation activity. Cancer Res 57: 2668-2675.

34. Turley JM, Sanders BG & Kline K (1995). Vitamin E succinate induction of HL-60 cell adhesion: a role for fibronectin and a 72-kDa fibronectin-binding molecule. Nutr Cancer 23: 43-54.

35. Yu W, Sanders BG & Kline K (1997). RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest. Nutr Cancer 27: 92-101.

36. Zhao B, Yu W, Qian M, Simmons Menchaca M, Brown P, Birrer MJ, Sanders BG & Kline K (1997). Involvement of activator protein-1 (AP-1) in induction of apoptosis by vitamin E succinate in human breast cancer cells. Mol Carcinog 19: 180-190.

37. Zou H, Henzel WJ, Liu X, Lutschg A & Wang X (1997). Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90: 405-413.

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