Toxicity and adverse effects of Tamoxifen and other anti-estrogen drugs

Pharmacology and Therapeutics

Volumn 139, Issue 3, 2013, Pages 392-404

  Yang, Geniey ^a   Nowsheen, Somaira ^b   Aziz, Khaled ^b   Georgakilas, Alexandros G ^a,c  

^a EAST CAROLINA UNIVERSITY   (United States)

^b MAYO CLINIC   (United States)

^c NATIONAL TECHNICAL UNIVERSITY OF ATHENS   (Greece)

Author keywords

Anti estrogen therapy; Breast cancer; DNA damage; Oxidative stress; Tamoxifen

Indexed keywords

CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; ENDOXIFEN; FLUOROURACIL; METHOTREXATE; PACLITAXEL; PERTUZUMAB; TAMOXIFEN; TRASTUZUMAB;

BREAST CANCER; BREAST METASTASIS; CANCER COMBINATION CHEMOTHERAPY; DIET; DRUG MECHANISM; EPIGENETICS; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; EXERCISE; HORMONAL THERAPY; HUMAN; OBESITY; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; UNSPECIFIED SIDE EFFECT;

ACTIVATION FUNCTION-1; AF-1; ANTI-ESTROGEN THERAPY; BCPT; BMI; BODY MASS INDEX; BREAST CANCER; BREAST CANCER PREVENTION TRIAL; DBD; DNA DAMAGE; DNA-BINDING DOMAIN; EGF RECEPTORS; EGFR; ER; ERES; ESTROGEN RECEPTOR; ESTROGEN RESPONSE ELEMENTS; FDA; FOOD AND DRUG ADMINISTRATION; HATS; HDACS; HER2; HISTONE ACETYLTRANSFERASES; HISTONE DEACETYLASES; HOMOLOGOUS RECOMBINATION; HR; HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2; ICI; IMPERIAL CHEMICAL INDUSTRIES; LBD; LIGAND-BINDING DOMAIN; NATIONAL SURGICAL ADJUVANT BREAST AND BOWEL PROJECT; NSABP; OXIDATIVE STRESS; PR; PROGESTERONE RECEPTOR; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN SPECIES; RNS; ROS; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SERM; TAM; TAMOXIFEN; TOR; TORIMEFENE;

ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; CYTOCHROME P-450 CYP2D6; ESTROGEN ANTAGONISTS; FEMALE; HUMANS; NEOPLASM METASTASIS; RECURRENCE; TAMOXIFEN;

EID: 84881231324     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2013.05.005     Document Type: Review

References (95)

1. D.B. Agus, M.S. Gordon, C. Taylor, R.B. Natale, B. Karlan, and D.S. Mendelson Phase I clinical study of pertuzumab, a novel her dimerization inhibitor, in patients with advanced cancer J Clin Oncol 23 2005 2534 2543 (Pubitemid 47050843)
2. A. Ashworth A synthetic lethal therapeutic approach: Poly (ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair J Clin Oncol 26 2008 3785 3790
3. K. Aziz, S. Nowsheen, G. Pantelias, G. Iliakis, V.G. Gorgoulis, and A.G. Georgakilas Targeting DNA damage and repair: Embracing the pharmacological era for successful cancer therapy Pharmacol Ther 133 2012 334 350
4. J. Baselga, K.A. Gelmon, S. Verma, A. Wardley, P. Conte, and D. Miles Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy J Clin Oncol 28 2010 1138 1144
5. V. Birgisdottir, O. Stefansson, S. Bodvarsdottir, H. Hilmarsdottir, J. Jonasson, and J. Eyfjord Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer Breast Cancer Res 8 2006 R38
6. C. Bouchardy, S. Benhamou, R. Schaffar, H.M. Verkooijen, G. Fioretta, and H. Schubert Lung cancer mortality risk among breast cancer patients treated with antiestrogens Cancer 117 2011 1288 1295
7. N. Brown, and R. Bicknell Hypoxia and oxidative stress in breast cancer: Oxidative stress - Its effects on the growth, metastatic potential and response to therapy of breast cancer Breast Cancer Res 3 2001 323 327 (Pubitemid 32851163)
8. H.E. Bryant, N. Schultz, H.D. Thomas, K.M. Parker, D. Flower, and E. Lopez Specific killing of BRCA2-deficient tumours with inhibitors of poly (ADP-ribose) polymerase Nature 434 2005 913 917 (Pubitemid 40559005)
9. S. Caltagirone, F.O. Ranelletti, A. Rinelli, N. Maggiano, A. Colasante, and P. Musiani Interaction with type II estrogen binding sites and antiproliferative activity of tamoxifen and quercetin in human non-small-cell lung cancer Am J Respir Cell Mol Biol 17 1997 51 59 (Pubitemid 127500820)
10. A. Cebrian, P.D. Pharoah, S. Ahmed, S. Ropero, M.F. Fraga, and P.L. Smith Genetic variants in epigenetic genes and breast cancer risk Carcinogenesis 27 2006 1661 1669 (Pubitemid 44303919)
11. E. Coezy, J.-L. Borgna, and H. Rochefort Tamoxifen and metabolites in MCF7 cells: Correlation between binding to estrogen receptor and inhibition of cell growth Cancer Res 42 1982 317 323 (Pubitemid 12207285)
12. V. Craig Jordan Antiestrogenic action of raloxifene and tamoxifen: Today and tomorrow J Natl Cancer Inst 90 1998 967 971
13. S.R. Cummings, S. Eckert, K.A. Krueger, D. Grady, T.J. Powles, and J.A. Cauley The effect of raloxifene on risk of breast cancer in postmenopausal women JAMA 281 1999 2189 2197
14. K. Dhingra Antiestrogens - Tamoxifen, SERMs and beyond Invest New Drugs 17 1999 285 311 (Pubitemid 30037960)
15. A. Dobrovic, and D. Simpfendorfer Methylation of the brca1 gene in sporadic breast cancer Cancer Res 57 1997 3347 3350 (Pubitemid 27355472)
16. W.L. Donegan, and P.N. Redlich Breast cancer in men Surg Clin North Am 76 1996 343 363 (Pubitemid 26119153)
17. M. Dutertre, and C.L. Smith Molecular mechanisms of selective estrogen receptor modulator (SERM) action J Pharmacol Exp Ther 295 2000 431 437
18. A.H. Eliassen, G.A. Colditz, B. Rosner, W.C. Willett, and S.E. Hankinson Adult weight change and risk of postmenopausal breast cancer JAMA 296 2006 193 201 (Pubitemid 44050373)
19. N.A. Ellis, and K. Offit Heterozygous mutations in DNA repair genes and hereditary breast cancer: A question of power PLoS Genet 8 2012 e1003008
20. L.W. Ellisen PARP inhibitors in cancer therapy: Promise, progress and puzzles Cancer Cell 19 2011 165
21. H. Farmer, N. McCabe, C.J. Lord, A.N.J. Tutt, D.A. Johnson, and T.B. Richardson Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Nature 434 2005 917 921 (Pubitemid 40559006)
22. M.G. FitzGerald, D.J. MacDonald, M. Krainer, I. Hoover, E. O'Neil, and H. Unsal Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer N Engl J Med 334 1996 143 149 (Pubitemid 26017951)
23. J.L. Freudenheim, J.R. Marshall, J.E. Vena, R. Laughlin, J.R. Brasure, and M.K. Swanson Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients J Natl Cancer Inst 88 1996 340 348 (Pubitemid 26094240)
24. U. Güth, D. Müller, D.J. Huang, E. Obermann, and H. Müller Strictly defined familial male breast cancer Fam Cancer 10 2011 73 77
25. H.A. Harvey, M. Kimura, and A. Hajba Toremifene: An evaluation of its safety profile Breast 15 2006 142 157 (Pubitemid 44268919)
26. P. Hirsimäki, A. Aaltonen, and E. Mäntylä Toxicity of antiestrogens Breast J 8 2002 92 96 (Pubitemid 34233587)
27. M.D. Holmes, W.Y. Chen, D. Feskanich, C.H. Kroenke, and G.A. Colditz Physical activity and survival after breast cancer diagnosis JAMA 293 2005 2479 2486 (Pubitemid 40705729)
28. M.D. Holmes, D.J. Hunter, G.A. Colditz, M.J. Stampfer, S.E. Hankinson, and F.E. Speizer Association of dietary intake of fat and fatty acids with risk of breast cancer JAMA 281 1999 914 920 (Pubitemid 29124635)
29. A. Howell, J.F.R. Robertson, P. Abram, M.R. Lichinitser, R. Elledge, and E. Bajetta Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: A multinational, double-blind, randomized trial J Clin Oncol 22 2004 1605 1613 (Pubitemid 41079798)
30. A. Howell, J.F.R. Robertson, J. Quaresma Albano, A. Aschermannova, L. Mauriac, and U.R. Kleeberg Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment J Clin Oncol 20 2002 3396 3403
31. N. Howlader, A.M. Noone, M. Krapcho, N. Neyman, R. Aminou, and S.F. Altekruse SEER cancer statistics review 1975-2009 NIH publication 2012 U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute Bethesda, MD.
32. Z. Huang, S.E. Hankinson, G.A. Colditz, M.J. Stampfer, D.J. Hunter, and J.E. Manson Dual effects of weight and weight gain on breast cancer risk JAMA 278 1997 1407 1411 (Pubitemid 27475968)
33. D.J. Hunter, D. Spiegelman, H.-O. Adami, L. Beeson, P.A. van den Brandt, and A.R. Folsom Cohort studies of fat intake and the risk of breast cancer - A pooled analysis N Engl J Med 334 1996 356 361 (Pubitemid 26049588)
34. S.R.D. Johnston Selective oestrogen receptor modulators and downregulators for breast cancer - Have they lost their way Breast Cancer Res 7 2005 119 130 (Pubitemid 40704133)
35. S.R.D. Johnston, G. Saccani-Jotti, I.E. Smith, J. Salter, J. Newby, and M. Coppen Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer Cancer Res 55 1995 3331 3338
36. V.C. Jordan The development of tamoxifen for breast cancer therapy: A tribute to the late Arthur L. Walpole Breast Cancer Res Treat 11 1988 197 209
37. V.C. Jordan Tamoxifen: A most unlikely pioneering medicine Nat Rev Drug Discov 2 2003 205 213 (Pubitemid 37361665)
38. H.M. Kantarjian, R.A. Wolff, and C.A. Koller Male breast cancer The MD Anderson Manual of Medical Oncology 2nd ed. 2011 McGraw-Hill 284-284
39. A. Kärki, E. Mäntylä, Y. Hirsimäki, S. Karlsson, S. Toikkanen, and P. Hirsimäki Comparison of the effects of tamoxifen and toremifene on rat hepatocarcinogenesis Arch Toxicol 74 2000 249 256
40. B.S. Katzenellenbogen Mechanisms of action and cross-talk between estrogen receptor and progesterone receptor pathways J Soc Gynecol Investig 7 2000 S33 S37
41. Ü. Korucuoǧlu, B. Çiftçi, Ö. Gülbahar, A. Biri, T. Nas, and R. Gürsoy Assessment of protein oxidation in women using raloxifene Mol Cell Biochem 290 2006 97 101 (Pubitemid 44473239)
42. J.S. Lee, S. Wacholder, J.P. Struewing, M. McAdams, D. Pee, and L.C. Brody Survival after breast cancer in Ashkenazi Jewish brca1 and brca2 mutation carriers J Natl Cancer Inst 91 1999 259 263 (Pubitemid 29090995)
43. Y.-W. Leu, P.S. Yan, M. Fan, V.X. Jin, J.C. Liu, and E.M. Curran Loss of estrogen receptor signaling triggers epigenetic silencing of downstream targets in breast cancer Cancer Res 64 2004 8184 8192 (Pubitemid 39491754)
44. A.S. Levenson, and V.C. Jordan The key to the antiestrogenic mechanism of raloxifene is amino acid 351 (aspartate) in the estrogen receptor Cancer Res 58 1998 1872 1875 (Pubitemid 28217461)
45. D. Li, Y. Dragan, V.C. Jordan, M. Wang, and H.C. Pitot Effects of chronic administration of tamoxifen and toremifene on DNA adducts in rat liver, kidney, and uterus Cancer Res 57 1997 1438 1441 (Pubitemid 27175557)
46. S.M. Lippman, and P.H. Brown Tamoxifen prevention of breast cancer: An instance of the fingerpost J Natl Cancer Inst 91 1999 1809 1819
47. D.M. Lonard, and C.L. Smith Molecular perspectives on selective estrogen receptor modulators (SERMs): Progress in understanding their tissue-specific agonist and antagonist actions Steroids 67 2002 15 24 (Pubitemid 33112000)
48. M.B. Marttunen, P. Hietanen, A. Tiitinen, and O. Ylikorkala Comparison of effects of tamoxifen and toremifene on bone biochemistry and bone mineral density in postmenopausal breast cancer patients J Clin Endocrinol Metab 83 1998 1158 1162 (Pubitemid 28496385)
49. N. McCarthy Breast cancer: Genes, genes everywhere Nat Rev Cancer 12 2012 507-507
50. M.T. McDermott, F.D. Hofeldt, and G.S. Kidd Tamoxifen therapy for painful idiopathic gynecomastia South Med J 83 1990 1283 1285
51. D.P. McDonnell The molecular pharmacology of SERMs Trends Endocrinol Metab 10 1999 301 311
52. A. McTiernan, C. Kooperberg, E. White, S. Wilcox, R. Coates, and L.L. Adams-Campbell Recreational physical activity and the risk of breast cancer in postmenopausal women JAMA 290 2003 1331 1336
53. A.M. Mendes Pereira, S.A. Martin, R. Brough, A. McCarthy, J.R. Taylor, and J.S. Kim Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors EMBO Mol Med 1 2009 315 322
54. L.M. Mielnicki, H.L. Asch, and B.B. Asch Genes, chromatin, and breast cancer: An epigenetic tale J Mammary Gland Biol Neoplasia 6 2001 169 182
55. Y. Miki, J. Swensen, D. Shattuck-Eidens, P. Futreal, K. Harshman, and S. Tavtigian A strong candidate for the breast and ovarian cancer susceptibility gene brca1 Science 266 1994 66 71 (Pubitemid 24345325)
56. R. Nahta, M.-C. Hung, and F.J. Esteva The her-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells Cancer Res 64 2004 2343 2346 (Pubitemid 38523885)
57. R.R. Nazarewicz, W.J. Zenebe, A. Parihar, S.K. Larson, E. Alidema, and J. Choi Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase Cancer Res 67 2007 1282 1290
58. P. Neven, R. Paridaens, G. Pelgrims, M. Martens, A. Bols, and J. Goeminne Fulvestrant (Faslodex™) in advanced breast cancer: Clinical experience from a Belgian cooperative study Breast Cancer Res Treat 109 2008 59 65 (Pubitemid 351538758)
59. S. Nowsheen, T. Cooper, J.A. Bonner, A.F. Lobuglio, and E.S. Yang HER2 overexpression renders human breast cancers sensitive to PARP inhibition independently of any defect in homologous recombination DNA repair Cancer Res 72 2012 4796 4806
60. C.K. Osborne Tamoxifen in the treatment of breast cancer N Engl J Med 339 1998 1609 1618 (Pubitemid 28536137)
61. C.K. Osborne, E.B. Coronado-Heinsohn, S.G. Hilsenbeck, B.L. McCue, A.E. Wakeling, and R.A. McCleland Comparison of the effects of a pure steroidal antiestrogen with those of tamoxifen in a model of human breast cancer J Natl Cancer Inst 87 1995 746 750
62. C.K. Osborne, and S.A.W. Fuqua Mechanisms of tamoxifen resistance Breast Cancer Res Treat 32 1994 49 55 (Pubitemid 24322247)
63. C.K. Osborne, and R. Schiff Growth factor receptor cross-talk with estrogen receptor as a mechanism for tamoxifen resistance in breast cancer Breast 12 2003 362 367 (Pubitemid 38008644)
64. G. Pagano, A. de Biase, I.B. Deeva, P. Degan, Y.K. Doronin, and M. Iaccarino The role of oxidative stress in developmental and reproductive toxicity of tamoxifen Life Sci 68 2001 1735 1749 (Pubitemid 32245622)
65. L.N. Parker, D.R. Gray, M.K. Lai, and E.R. Levin Treatment of gynecomastia with tamoxifen: A double-blind crossover Metabolism 35 1986 705 708 (Pubitemid 16040621)
66. D.H. Phillips, P.L. Carmichael, A. Hewer, K.J. Cole, I.R. Hardcastle, and G.K. Poon Activation of tamoxifen and its metabolite α- hydroxytamoxifen to DNA-binding products: Comparisons between human, rat and mouse hepatocytes Carcinogenesis 17 1996 89 94 (Pubitemid 26091275)
67. A.C.W. Pike, A.M. Brzozowski, J. Walton, R.E. Hubbard, A.-G. Thorsell, and Y.-L. Li Structural insights into the mode of action of a pure antiestrogen Structure 9 2001 145 153 (Pubitemid 32215278)
68. K. Polyak Heterogeneity in breast cancer J Clin Invest 121 2011 3786 3788
69. C.f.D.C. a Prevention Cancer facts & figures 2012 American Cancer Society Inc.
70. J.D. Ribaya-Mercado, and J.B. Blumberg Lutein and zeaxanthin and their potential roles in disease prevention J Am Coll Nutr 23 2004 567S 587S (Pubitemid 40096745)
71. W. Scheuer, T. Friess, H. Burtscher, B. Bossenmaier, J. Endl, and M. Hasmann Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on her2-positive human xenograft tumor models Cancer Res 69 2009 9330 9336
72. R. Schiff, P. Reddy, M. Ahotupa, E. Coronado-Heinsohn, M. Grim, and S.G. Hilsenbeck Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo J Natl Cancer Inst 92 2000 1926 1934 (Pubitemid 32036923)
73. A.K. Shiau, D. Barstad, P.M. Loria, L. Cheng, P.J. Kushner, and D.A. Agard The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen Cell 95 1998 927 937 (Pubitemid 29019045)
74. S. Shibutani, A. Ravindernath, I. Terashima, N. Suzuki, Y.R. Santosh Laxmi, and Y. Kanno Mechanism of lower genotoxicity of toremifene compared with tamoxifen Cancer Res 61 2001 3925 3931 (Pubitemid 32720952)
75. S. Shibutani, N. Suzuki, Y.R.S. Laxmi, L.J. Schild, R.L. Divi, and A.P. Grollman Identification of tamoxifen-DNA adducts in monkeys treated with tamoxifen Cancer Res 63 2003 4402 4406 (Pubitemid 36951010)
76. R. Siegel, D. Naishadham, and A. Jemal Cancer statistics, 2012 CA Cancer J Clin 62 2012 10 29
77. V. Stearns, and E. Gelmann Does tamoxifen cause cancer in humans? J Clin Oncol 16 1998 779 792 (Pubitemid 28135628)
78. A.Z. Steiner, M. Terplan, and R.J. Paulson Comparison of tamoxifen and clomiphene citrate for ovulation induction: A meta-analysis Hum Reprod 20 2005 1511 1515 (Pubitemid 40852240)
79. M.R. Stratton, D. Ford, S. Neuhasen, S. Seal, R. Wooster, and L.S. Friedman Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q Nat Genet 7 1994 103 107 (Pubitemid 24232389)
80. M. Suganuma, S. Okabe, Y. Kai, N. Sueoka, E. Sueoka, and H. Fujiki Synergistic effects of (-)-epigallocatechin gallate with (-)-epicatechin, sulindac, or tamoxifen on cancer-preventive activity in the human lung cancercell line PC-9 Cancer Res 59 1999 44 47 (Pubitemid 29062952)
81. M. Thangaraju, T. Vijayalakshimi, and P. Sachdanandam Effect of tamoxifen on lipid peroxide and antioxidative system in postmenopausal women with breast cancer Cancer 74 1994 78 82 (Pubitemid 24187613)
82. D.B. Thomas, L. Margarita Jimenez, A. McTieman, K. Rosenblatt, H. Stalsberg, and A. Stemhagen Breast cancer in men: Risk factors with hormonal implications Am J Epidemiol 135 1992 734 748
83. V.K. Todorova, Y. Kaufmann, S. Luo, and V. Suzanne Klimberg Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake Cancer Chemother Pharmacol 67 2011 285 291
84. P. Tonin, B. Weber, K. Offit, F. Couch, T.R. Rebbeck, and S. Neuhausen Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families Nat Med 2 1996 1179 1183 (Pubitemid 26375392)
85. A. Trentham-Dietz, P.A. Newcomb, B.E. Storer, M.P. Longnecker, J. Baron, and E.R. Greenberg Body size and risk of breast cancer Am J Epidemiol 145 1997 1011 1019 (Pubitemid 27215484)
86. J. Vetto, S.-Y. Jun, D. Padduch, H. Eppich, and R. Shih Stages at presentation, prognostic factors, and outcome of breast cancer in males Am J Surg 177 1999 379 383 (Pubitemid 29252805)
87. V.G. Vogel, J.P. Costantino, D.L. Wickerham, W.M. Cronin, R.S. Cecchini, and J.N. Atkins Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes JAMA 295 2006 2727 2741
88. P.A. Wade Transcriptional control at regulatory checkpoints by histone deacetylases: Molecular connections between cancer and chromatin Hum Mol Genet 10 2001 693 698 (Pubitemid 32331577)
89. E. Warner, W. Foulkes, P. Goodwin, W. Meschino, J. Blondal, and C. Paterson Prevalence and penetrance of brca1 and brca2 gene mutations in unselected Ashkenazi Jewish women with breast cancer J Natl Cancer Inst 91 1999 1241 1247 (Pubitemid 29357191)
90. P.C. Willsher, I.H. Leach, I.O. Ellis, J.B. Bourke, R.W. Blamey, and J.F.R. Robertson A comparison outcome of male breast cancer with female breast cancer Am J Surg 173 1997 185 188 (Pubitemid 27163845)
91. E.S. Yang, S. Nowsheen, M.A. Rahman, R.S. Cook, and F. Xia Targeting BRCA1 localization to augment breast tumor sensitivity to poly(ADP-ribose) polymerase inhibition Cancer Res 72 2012 5547 5555
92. S. Yuvaraj, V.G. Premkumar, K. Vijayasarathy, S.G.D. Gangadaran, and P. Sachdanandam Augmented antioxidant status in tamoxifen treated postmenopausal women with breast cancer on co-administration with coenzyme Q 10, niacin and riboflavin Cancer Chemother Pharmacol 61 2008 933 941 (Pubitemid 351423120)
93. S. Zhang, D.J. Hunter, M.R. Forman, B.A. Rosner, F.E. Speizer, and G.A. Colditz Dietary carotenoids and vitamins A, C, and E and risk of breast cancer J Natl Cancer Inst 91 1999 547 556 (Pubitemid 29157064)
94. D. Ziech, I. Anestopoulos, R. Hanafi, G.P. Voulgaridou, R. Franco, and A.G. Georgakilas Pleiotrophic effects of natural products in ROS-induced carcinogenesis: The role of plant-derived natural products in oral cancer chemoprevention Cancer Lett 327 2012 16 25
95. D. Ziech, R. Franco, A. Pappa, V. Malamou-Mitsi, S. Georgakila, and A.G. Georgakilas The role of epigenetics in environmental and occupational carcinogenesis Chem Biol Interact 188 2010 340 349