Tamoxifen pp 321-341 | Cite as

Membrane Antioxidant-Mediated Cardioprotective Anticarcinogenic Actions of Tamoxifen

  • Helen Wiseman

Abstract

In order to understand the possible importance of the reported membrane antioxidant action of Tamoxifen to its cardioprotective and anticarcinogenic effects, the basics of membrane and lipoprotein composition and structure and how these are influences by free radicalmediated oxidative stress need to be appreciated and these will now be briefly explored (see Figure 1 for an overview).

Keywords

Estrogen Foam Osteoporosis Glutathione Ozone 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ames BN (1989): Endogenous oxidative DNA damage, aging and cancer. Free Rad Res Communs 7:121–128CrossRefGoogle Scholar
  2. Anker G, Lonning PE, Ueland PM, Refsum H and Lein EA (1995): Plasma levels of the atherogenic amino acid homocysteine in post-menopausal women with breast cancer treated with tamoxifen. Int J Cancer 60:365–368PubMedCrossRefGoogle Scholar
  3. Bruning PE (1992): Droloxifene, a new anti-oestrogen in postmenopausal advanced breast cancer: preliminary results of a double-blind dose-finding study phase II trial. Eur J Cancer 28A: 1404–1407PubMedCrossRefGoogle Scholar
  4. Boyd NF and McGuire V (1991): The possible role of lipid peroxidation in breast cancer risk. Free Rad Biol Med 10:185–190PubMedCrossRefGoogle Scholar
  5. Cerutti P (1994): Oxy-radicals and cancer. Lancet 344:862–863PubMedCrossRefGoogle Scholar
  6. Chatterjee SN and Agarwal S (1988): Liposomes as a membrane model for study of lipid peroxidation. Free Rad Biol Med 4:51–72PubMedCrossRefGoogle Scholar
  7. Darley-Usmar V, Wiseman H and Halliwell (1995): Nitric oxide and oxygen radicals: A question of balance. FEBS Lett (in press)Google Scholar
  8. Dean RT, Gieseg S and Davies MJ (1993): Reactive species and their accumulation on radical-damaged proteins. Trends Biochem Sci 18:437–441PubMedCrossRefGoogle Scholar
  9. De Friend DJ, Howell A, Nicholson RI, Anderson E, Dowsett M, Mansel RE, Blarney RW, Bundred NJ, Robertson JF, Saunders C, Baum M, Walton P, Sutcliffe F and Wakeling AE (1994): Investigation of a new pure antioestrogen (ICI 182 780) in women with primary breast cancer. Cancer Res 54:408–414Google Scholar
  10. Dowsett M, Johnston SRD, Iveson TJ and Smith IE (1995): Response to specific anti-oestrogen (ICI 182 780) in tamoxifen-resistant breast cancer. Lancet 345:525PubMedCrossRefGoogle Scholar
  11. Esterbauer H (1993): Cytotoxicity and genotoxicity of lipid-oxidation products. Am J Clin Nutr (suppl) 57:779s-786sGoogle Scholar
  12. Esterbauer H, Gebicki J, Puhl H and Jurgens G (1992): The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Rad Biol Med 13:341–390PubMedCrossRefGoogle Scholar
  13. Frei B (1995): Cardiovascular disease and nutrient antioxidants: Role of low- density lipoprotein oxidation. Critical Reviews in Food Science and Nutrition 35:83–98PubMedCrossRefGoogle Scholar
  14. Gelety TJ and Judd HL (1992): Menopause: new indications and management strategies. Curr Opin Obstet Gynecol 4:346–353PubMedGoogle Scholar
  15. Gey KF (1995): Ten-year retrospective on the antioxidant hypothesis of arteriosclerosis: Threshold plasma levels of antioxidant micronutrients related to minimum cardiovascular risk. J Nutr Biochem 6:206–236CrossRefGoogle Scholar
  16. Girelli D, Olivieri O, Stanzial AM, Guarini P, Trevisan MT, Bassi A and Corrocher R (1994): Factors affecting the thiobarbituric acid test as index of red blood cell suspectibility to lipid peroxidation: A multivariate analysis. Clin Chim Acta 227:45–57PubMedCrossRefGoogle Scholar
  17. Gurr MI and Harwood JL (1991): Lipid Biochemistry: An Introduction. 4th ed. London: Chapman and HallCrossRefGoogle Scholar
  18. Gutteridge JMC (1993): Free radicals in disease processes: A complication of cause and consequence. Free Rad Res Communs 19:141–158CrossRefGoogle Scholar
  19. Gutteridge JMC and Halliweli B (1994): Antioxidants in Nutrition, Health and Disease. Oxford: Oxford University PressGoogle Scholar
  20. Halliweli B (1990): How to characterize a biological antioxidant. Free Rad Res Commun 9:1–32CrossRefGoogle Scholar
  21. Halliweli B (1993): The role of oxygen radicals in human disease, with particular reference to the vascular system. Haemostasis (suppl) 23:118–126Google Scholar
  22. Halliweli B (1994): Free radicals and antioxidants: a personal view. Nutrition Reviews 52:253–265CrossRefGoogle Scholar
  23. Halliweli B and Chirico S (1993): Lipid peroxidation: Its mechanism, measurement and significance. Am J Clin Nutr 57:15S-25SGoogle Scholar
  24. Halliweli B and Gutteridge JMC (1989): Free Radical Biology and Medicine 2nd edition. Oxford: Clarendon PressGoogle Scholar
  25. Hasmann M, Rattel B and Loser (1994): Preclinical data for droloxifene. Cancer Lett 84:101–116PubMedCrossRefGoogle Scholar
  26. Hay den MR and Reidy M (1995): Many roads lead to atheroma. Nature Med 1:22–23CrossRefGoogle Scholar
  27. Hirano K, Ogihara T, Miki M, Yauda H, Tamai H, Kawamura N and Mino M (1994): Homocysteine induces iron-catalysed lipid peroxidation of low-density lipoprotein that is prevented by alpha-tocopherol. Free Rad Res 21:267–276CrossRefGoogle Scholar
  28. Jones AL and Powles TJ (1992): The development of cancer chemoprevention trials. In: Introducing New Treatments for Cancer Practical, Ethical and Legal Problems. Williams CJ, ed. Chichester: John Wiley & SonsGoogle Scholar
  29. Lim JS, Frenkel K and Toll W (1992): Tamoxifen supresses tumour promoter- induced hydrogen peroxide formation by human neutrophils. Cancer Res 52:4969–4972PubMedGoogle Scholar
  30. Love RR, Wiebe DA, Feyzi JM, Newcombe PA and Chappell RJ (1994): Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 5 years of treatment. J Natl Cancer Institute 86:1534–1537CrossRefGoogle Scholar
  31. Love RR, Surawicz TS and Williams EC (1992): Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy. Arch Int Med 152:317–320CrossRefGoogle Scholar
  32. Love RR, Wiebe DA, Newcombe PA, Cameron L, Leventhal H, Jordan VC, Feyzi J and DeMets DL (1991): Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann Intern Med 15:860–864Google Scholar
  33. Malins DC, and Haimanot R (1991): Major alterations in the nucleotide structure of DNA in cancer of the female breast. Cancer Res 51:5430–5432PubMedGoogle Scholar
  34. Malins DC, Holmes EH, Polissar NL and Gunselman SJ (1993): The etiology of breast cancer: Characteristic alterations in hydroxyl radical-induced DNA base lesions during oncogenesis with potential for evaluating incidence of risk. Cancer 71:3036–3043PubMedCrossRefGoogle Scholar
  35. McDonald CC and Stewart HJ (1991): Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. Br Med J 303:435–437CrossRefGoogle Scholar
  36. Miller VT (1994): Lipids, lipoproteins, women and cardiovascular disease. Atherosclerosis (suppl) 108: S73-S82PubMedCrossRefGoogle Scholar
  37. Neuzil J, Gebicki JM and Stocker R (1993): Radical-induced chain oxidation of proteins and its inhibition by chain-breaking antioxidants. Bioehem J 293:601–606Google Scholar
  38. New RRC (1992): Liposomes: A practical approach. Oxford: IRL PressGoogle Scholar
  39. Parthasarathy S and Santanam N (1994): Mechanism of oxidation, antioxidants and atherosclerosis. Curr Opin Lipodol 5:371–375CrossRefGoogle Scholar
  40. Peck MD (1994): Interactions of lipids with immune function I: Biochemical effects of dietary lipids on plasma membranes. J Nutr Bioehem 5:466–478CrossRefGoogle Scholar
  41. Powles TJ, Tillyer CR, Jones AL, Treleavan J, Davey JB, McKinna JA (1990): Prevention of breast cancer with tamoxifen: An update of the Royal Marsden Hospital pilot programme. Eur J Cancer 6:680–684Google Scholar
  42. Rice-Evans CA and Bruckdorfer KR (1992): Free radicals, lipoproteins and cardiovascular dysfunction. Molec Aspects Med 13:1–111CrossRefGoogle Scholar
  43. Rifici VA and Khachadurian AK (1992): The inhibition of low-density lipoprotein oxidation by 17 B-estradiol. Metabolism 41:1110–1114PubMedCrossRefGoogle Scholar
  44. Rutqvist LE and Mattsson A (1993): Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. The Stockhom Breast Cancer Study Group. J Natl Cancer Inst 85:1398–1406PubMedCrossRefGoogle Scholar
  45. Sack MN, Rader DJ and Cannon RO (1994): Oesterogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. Lancet 343:269–270PubMedCrossRefGoogle Scholar
  46. Schapira DV, Kumar NB and Lyman GH (1990): Serum cholesterol reduction with tamoxifen. Breast Cancer Res Treat 17:3–7PubMedCrossRefGoogle Scholar
  47. Shewmon DA, Stoch JL, Abusamra LC, Kristan MA, Baker S and Heiniluoma KM (1994): Tamoxifen decreased lipoprotein(a) in patients with breast cancer. Metabolism 43:531–532PubMedCrossRefGoogle Scholar
  48. Shewmon DA, Stock JL, Rosen CJ, Heiniluoma KM, Hogue MM, Morrison A, Doyle EM, Ukena T, Weale V and Baker S (1994): Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy postmenopausal women. Arterioscler Thromb 14:1586–1593PubMedCrossRefGoogle Scholar
  49. Smith C, Mitchinson M, Aruoma OI and Halliwell B (1992): Stimulation of lipid peroxidation and hydroxyl radical generation by the contents of human atherosclerotic lesions. Biochem J 286:901–905PubMedGoogle Scholar
  50. Stadtman ER (1993): Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalysed reactions. Ann Rev Biochem 62:797–821PubMedCrossRefGoogle Scholar
  51. Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE and Hennekens CH (1991): Postmenopausal estrogen therapy and cardiovascular disease: Ten-year follow-up from the nurses’ health study. New Engl J Med 325:756–762PubMedCrossRefGoogle Scholar
  52. Thomas JP, Kalyanaraman B and Girotti AW (1994): Involvement of preexisting lipid hydroperoxides in Cu2+-stimulated oxidation of low-density lipoprotein. Arch Biochem Biophys 315:244–254PubMedCrossRefGoogle Scholar
  53. Ueland PM, Refsum H and Brattstrom L (1992): Atherosclerotic cardiovascular disease, hemostasis and endothelial function. In: Plasma Homocysteine and Cardiovascular Disease. Francis RB ed. New York: Marcel Dekker Inc.Google Scholar
  54. Wakeling AE (1993): The future of new pure antioestrogens in clinical breast cancer. Breast Cancer Res Treat 25:1–10PubMedCrossRefGoogle Scholar
  55. Wei H and Frenkel K (1993): Relationship of oxidative events and DNA oxidation in SENCAR mice to in vivo promoting activity of phorbol estertype tumour promoters. Carcinogenesis 14:195–201CrossRefGoogle Scholar
  56. Williamson P and Schegel RA (1994): Back and forth: the regulation and function of transbilayer phospholipid movement in eukaryotic cells. Molec Membrane Biol 11:199–216CrossRefGoogle Scholar
  57. Wiseman H (1994a): Tamoxifen: Molecular Basis of Use in Cancer Treatment and Prevention. Chichester: John Wiley & SonsGoogle Scholar
  58. Wiseman H (1994b): Tamoxifen: new membrane-mediated mechanisms of action and therapeutic advances. Trends Pharmacol Sci 15:83–89PubMedCrossRefGoogle Scholar
  59. Wiseman H (1994c): The antioxidant action of a pure antiestrogen: Ability to inhibit lipid peroxidation compared to tamoxifen and 17B-oestradiol and relevance to its anticancer potential. Biochem Pharmacol 47:493–498PubMedCrossRefGoogle Scholar
  60. Wiseman H (1994d): Tamoxifen and estrogens as membrane antioxidants: Comparison with cholesterol. Methods in Enzymology Vol. 234 Oxygen Radicals in Biological Systems Part D Packer L ed. San Diego: Academic PressGoogle Scholar
  61. Wiseman H (1995): Tamoxifen as an antioxidant and cardioprotectant. In: Biochemical Society Symposium 61, Free radicals and oxidative stress: environment drugs and food additives, Rice-Evans C and Halliwell B eds. Lond: ortland PressGoogle Scholar
  62. Wiseman H and Halliwell B (1993): Carcinogenic antioxidants: Diethylstilboestrol, hexoestrol and 17 alpha-ethynyloestradiol. FEBS Lett 332:159–163PubMedCrossRefGoogle Scholar
  63. Wiseman H and Halliwell B (1994): Tamoxifen and related compounds protect against lipid peroxidation in isolated nuclei: Relevance to the potential anticarcinogenic benefits of breast cancer prevention and therapy with tamoxifen. Free Rod Biol Med 17:485–488CrossRefGoogle Scholar
  64. Wiseman H and Halliwell B (1995): Damage to DNA by reactive oxygen and nitrogen species: Role in inflammatory disease and progression to cancer. Biochem J (in press)Google Scholar
  65. Wiseman H and Quinn P (1994): The antioxidant action of synthetic oestrogens involves decreased membrane fluidity: Relevance to their potential use as anticancer and cardioprotective agents compared to tamoxifen. Free Rad Res 21:187–194CrossRefGoogle Scholar
  66. Wiseman H, Arnstein HRV, Cannon M and Halliwell B (1990b): Mechanism of inhibition of lipid peroxidation by tamoxifen and 4-hydroxytamoxifen introduced into lipsomes: Similarity to cholesterol and ergosterol. FEBS Leu 274:107–110CrossRefGoogle Scholar
  67. Wiseman H, Cannon M, Arnstein HRV and Halliwell B (1993a): Tamoxifen inhibits peroxidation in cardiac microsomes: Comparison with liver microsomes and potential relevance to the cardiovascular benefits associated with cancer prevention and treatment by tamoxifen. Biochem Pharmacol 45:1851–1855PubMedCrossRefGoogle Scholar
  68. Wiseman H, Laughton MJ, Arnstein HRV, Cannon M and Halliwell B (1990a): The antioxidant action of tamoxifen and its metabolites. Inhibition of lipid peroxidation. FEBS Lett 263:192–194PubMedCrossRefGoogle Scholar
  69. Wiseman H, Smith C, Halliwell B, Cannon M, Arnstein HRV and Lennard MS (1992): Droloxifene (3-hydroxytamoxifen) has membrane antioxidant ability: Potential relevance to its mechanism of therapeutic action in breast cancer. Cancer Lett 66:61–68PubMedCrossRefGoogle Scholar
  70. Wiseman H, Paganga G, Rice-Evans C, Halliwell B (1993c): Protective actions of tamoxifen and 4-hydroxytamoxifen against oxidative damage to human low-density lipoproteins. A mechanism accounting for the cardioprotective action of tamoxifen? Biochem J 292:635–638PubMedGoogle Scholar
  71. Wiseman H, Quinn P, and Halliwell B (1993b): Tamoxifen and related compounds decrease membrane fluidity in liposomes. Mechanism for the antioxidant action of tamoxifen and relevance to its anticancer and cardioprotective actions? FEBS Lett 330:53–56PubMedCrossRefGoogle Scholar
  72. Witzum JL (1994): The oxidation hypothesis of atherosclerosis. Lancet 344:792–795Google Scholar
  73. Zachowski A (1993): Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J 294:1–14PubMedGoogle Scholar

Copyright information

© Birkhäuser Boston 1996

Authors and Affiliations

  • Helen Wiseman

There are no affiliations available

Personalised recommendations