Skip to main content
SpringerLink
Log in

Membrane Antioxidant-Mediated Cardioprotective Anticarcinogenic Actions of Tamoxifen

  • Chapter
Tamoxifen

  • 106 Accesses

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).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ames BN (1989): Endogenous oxidative DNA damage, aging and cancer. Free Rad Res Communs 7:121–128

    Article  CAS  Google Scholar 

  • 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 60:365–368

    Article  PubMed  CAS  Google Scholar 

  • 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: 1404–1407

    Article  PubMed  CAS  Google Scholar 

  • Boyd NF and McGuire V (1991): The possible role of lipid peroxidation in breast cancer risk. Free Rad Biol Med 10:185–190

    Article  PubMed  CAS  Google Scholar 

  • Cerutti P (1994): Oxy-radicals and cancer. Lancet 344:862–863

    Article  PubMed  CAS  Google Scholar 

  • Chatterjee SN and Agarwal S (1988): Liposomes as a membrane model for study of lipid peroxidation. Free Rad Biol Med 4:51–72

    Article  PubMed  CAS  Google Scholar 

  • Darley-Usmar V, Wiseman H and Halliwell (1995): Nitric oxide and oxygen radicals: A question of balance. FEBS Lett (in press)

    Google Scholar 

  • Dean RT, Gieseg S and Davies MJ (1993): Reactive species and their accumulation on radical-damaged proteins. Trends Biochem Sci 18:437–441

    Article  PubMed  CAS  Google Scholar 

  • 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 54:408–414

    Google Scholar 

  • Dowsett M, Johnston SRD, Iveson TJ and Smith IE (1995): Response to specific anti-oestrogen (ICI 182 780) in tamoxifen-resistant breast cancer. Lancet 345:525

    Article  PubMed  CAS  Google Scholar 

  • Esterbauer H (1993): Cytotoxicity and genotoxicity of lipid-oxidation products. Am J Clin Nutr (suppl) 57:779s-786s

    CAS  Google Scholar 

  • 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 13:341–390

    Article  PubMed  CAS  Google Scholar 

  • Frei B (1995): Cardiovascular disease and nutrient antioxidants: Role of low- density lipoprotein oxidation. Critical Reviews in Food Science and Nutrition 35:83–98

    Article  PubMed  CAS  Google Scholar 

  • Gelety TJ and Judd HL (1992): Menopause: new indications and management strategies. Curr Opin Obstet Gynecol 4:346–353

    PubMed  CAS  Google Scholar 

  • 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 6:206–236

    Article  CAS  Google Scholar 

  • 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 227:45–57

    Article  PubMed  CAS  Google Scholar 

  • Gurr MI and Harwood JL (1991): Lipid Biochemistry: An Introduction. 4th ed. London: Chapman and Hall

    Book  Google Scholar 

  • Gutteridge JMC (1993): Free radicals in disease processes: A complication of cause and consequence. Free Rad Res Communs 19:141–158

    Article  CAS  Google Scholar 

  • Gutteridge JMC and Halliweli B (1994): Antioxidants in Nutrition, Health and Disease. Oxford: Oxford University Press

    Google Scholar 

  • Halliweli B (1990): How to characterize a biological antioxidant. Free Rad Res Commun 9:1–32

    Article  Google Scholar 

  • Halliweli B (1993): The role of oxygen radicals in human disease, with particular reference to the vascular system. Haemostasis (suppl) 23:118–126

    Google Scholar 

  • Halliweli B (1994): Free radicals and antioxidants: a personal view. Nutrition Reviews 52:253–265

    Article  Google Scholar 

  • Halliweli B and Chirico S (1993): Lipid peroxidation: Its mechanism, measurement and significance. Am J Clin Nutr 57:15S-25S

    Google Scholar 

  • Halliweli B and Gutteridge JMC (1989): Free Radical Biology and Medicine 2nd edition. Oxford: Clarendon Press

    Google Scholar 

  • Hasmann M, Rattel B and Loser (1994): Preclinical data for droloxifene. Cancer Lett 84:101–116

    Article  PubMed  CAS  Google Scholar 

  • Hay den MR and Reidy M (1995): Many roads lead to atheroma. Nature Med 1:22–23

    Article  Google Scholar 

  • 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 21:267–276

    Article  CAS  Google Scholar 

  • 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 & Sons

    Google Scholar 

  • Lim JS, Frenkel K and Toll W (1992): Tamoxifen supresses tumour promoter- induced hydrogen peroxide formation by human neutrophils. Cancer Res 52:4969–4972

    PubMed  CAS  Google Scholar 

  • 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 86:1534–1537

    Article  CAS  Google Scholar 

  • Love RR, Surawicz TS and Williams EC (1992): Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy. Arch Int Med 152:317–320

    Article  CAS  Google Scholar 

  • 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 15:860–864

    Google Scholar 

  • Malins DC, and Haimanot R (1991): Major alterations in the nucleotide structure of DNA in cancer of the female breast. Cancer Res 51:5430–5432

    PubMed  CAS  Google Scholar 

  • 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 71:3036–3043

    Article  PubMed  CAS  Google Scholar 

  • McDonald CC and Stewart HJ (1991): Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. Br Med J 303:435–437

    Article  CAS  Google Scholar 

  • Miller VT (1994): Lipids, lipoproteins, women and cardiovascular disease. Atherosclerosis (suppl) 108: S73-S82

    Article  PubMed  Google Scholar 

  • Neuzil J, Gebicki JM and Stocker R (1993): Radical-induced chain oxidation of proteins and its inhibition by chain-breaking antioxidants. Bioehem J 293:601–606

    CAS  Google Scholar 

  • New RRC (1992): Liposomes: A practical approach. Oxford: IRL Press

    Google Scholar 

  • Parthasarathy S and Santanam N (1994): Mechanism of oxidation, antioxidants and atherosclerosis. Curr Opin Lipodol 5:371–375

    Article  CAS  Google Scholar 

  • Peck MD (1994): Interactions of lipids with immune function I: Biochemical effects of dietary lipids on plasma membranes. J Nutr Bioehem 5:466–478

    Article  CAS  Google Scholar 

  • 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 6:680–684

    Google Scholar 

  • Rice-Evans CA and Bruckdorfer KR (1992): Free radicals, lipoproteins and cardiovascular dysfunction. Molec Aspects Med 13:1–111

    Article  CAS  Google Scholar 

  • Rifici VA and Khachadurian AK (1992): The inhibition of low-density lipoprotein oxidation by 17 B-estradiol. Metabolism 41:1110–1114

    Article  PubMed  CAS  Google Scholar 

  • 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 85:1398–1406

    Article  PubMed  CAS  Google Scholar 

  • Sack MN, Rader DJ and Cannon RO (1994): Oesterogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. Lancet 343:269–270

    Article  PubMed  CAS  Google Scholar 

  • Schapira DV, Kumar NB and Lyman GH (1990): Serum cholesterol reduction with tamoxifen. Breast Cancer Res Treat 17:3–7

    Article  PubMed  CAS  Google Scholar 

  • Shewmon DA, Stoch JL, Abusamra LC, Kristan MA, Baker S and Heiniluoma KM (1994): Tamoxifen decreased lipoprotein(a) in patients with breast cancer. Metabolism 43:531–532

    Article  PubMed  CAS  Google Scholar 

  • 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 14:1586–1593

    Article  PubMed  CAS  Google Scholar 

  • 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 286:901–905

    PubMed  CAS  Google Scholar 

  • Stadtman ER (1993): Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalysed reactions. Ann Rev Biochem 62:797–821

    Article  PubMed  CAS  Google Scholar 

  • 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 325:756–762

    Article  PubMed  CAS  Google Scholar 

  • Thomas JP, Kalyanaraman B and Girotti AW (1994): Involvement of preexisting lipid hydroperoxides in Cu2+-stimulated oxidation of low-density lipoprotein. Arch Biochem Biophys 315:244–254

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Wakeling AE (1993): The future of new pure antioestrogens in clinical breast cancer. Breast Cancer Res Treat 25:1–10

    Article  PubMed  CAS  Google Scholar 

  • 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 14:195–201

    Article  Google Scholar 

  • Williamson P and Schegel RA (1994): Back and forth: the regulation and function of transbilayer phospholipid movement in eukaryotic cells. Molec Membrane Biol 11:199–216

    Article  CAS  Google Scholar 

  • Wiseman H (1994a): Tamoxifen: Molecular Basis of Use in Cancer Treatment and Prevention. Chichester: John Wiley & Sons

    Google Scholar 

  • Wiseman H (1994b): Tamoxifen: new membrane-mediated mechanisms of action and therapeutic advances. Trends Pharmacol Sci 15:83–89

    Article  PubMed  CAS  Google Scholar 

  • 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 47:493–498

    Article  PubMed  CAS  Google Scholar 

  • 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 Press

    Google Scholar 

  • 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 Press

    Google Scholar 

  • Wiseman H and Halliwell B (1993): Carcinogenic antioxidants: Diethylstilboestrol, hexoestrol and 17 alpha-ethynyloestradiol. FEBS Lett 332:159–163

    Article  PubMed  CAS  Google Scholar 

  • 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 17:485–488

    Article  CAS  Google Scholar 

  • 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 

  • 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 21:187–194

    Article  CAS  Google Scholar 

  • 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 274:107–110

    Article  CAS  Google Scholar 

  • 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 45:1851–1855

    Article  PubMed  CAS  Google Scholar 

  • 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 263:192–194

    Article  PubMed  Google Scholar 

  • 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 66:61–68

    Article  PubMed  CAS  Google Scholar 

  • 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 292:635–638

    PubMed  CAS  Google Scholar 

  • 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 330:53–56

    Article  PubMed  CAS  Google Scholar 

  • Witzum JL (1994): The oxidation hypothesis of atherosclerosis. Lancet 344:792–795

    Google Scholar 

  • Zachowski A (1993): Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J 294:1–14

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Helen Wiseman
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. 89 Rameau Drive, Toronto, Ontario, M2H 1T6, Canada

    John A. Kellen

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Birkhäuser Boston

About this chapter

Cite this chapter

Wiseman, H. (1996). Membrane Antioxidant-Mediated Cardioprotective Anticarcinogenic Actions of Tamoxifen. In: Kellen, J.A. (eds) Tamoxifen. Birkhäuser Boston. https://doi.org/10.1007/978-1-4612-4092-1_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-4092-1_14

  • Publisher Name: Birkhäuser Boston

  • Print ISBN: 978-1-4612-8648-6

  • Online ISBN: 978-1-4612-4092-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation