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Augmented antioxidant status in Tamoxifen treated postmenopausal women with breast cancer on co-administration with Coenzyme Q10, Niacin and Riboflavin

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Abstract

Background

Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide (H2O2), hydroxyl radical have been implicated in pathogenesis of various diseases including cancer and metastasis. Tamoxifen (TAM) is a non-steroidal anti-estrogen drug most widely used as an adjuvant hormonal therapy in breast cancer. TAM also has estrogenic activity on liver and endometrium causing severe oxidative stress and hypertriglycerdemia. Coenzyme Q10 (CoQ10), Niacin and Riboflavin are well-known potent antioxidants and protective agents against many diseases including cancer. In this context, this study was undertaken to find if co-administration of CoQ10, Niacin and Riboflavin along with TAM could augment the antioxidant (AO) status in postmenopausal women with breast cancer.

Methods

The vitamin supplementation with Tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma lipids, lipid peroxides and various circulating enzymatic and non-enzymatic antioxidants were estimated in 78 untreated, sole TAM treated and combinatorial treated group along with 46 age- and sex-matched controls.

Results

Enhanced oxidative stress as evidenced by increased lipids and lipid peroxides with decreased AO levels in untreated breast cancer patients was observed. Adjuvant TAM-treated group had a limited impact on the increased oxidative stress with decreased AO status. Severe hypertriglycerdemia was observed in TAM-treated group when compared to untreated and control subjects. Combinatorial therapy (CT) of CoQ10, Niacin and Riboflavin along with TAM decreased the oxidative stress and increased the AO status.

Conclusion

The antioxidant defense system is compromised in breast cancer patients. There is a shift in the oxidant / antioxidant balance in favor of lipid peroxidation (LPO), which could lead to tumour promotion observed in the disease. CT of CoQ10, Niacin and Riboflavin along with TAM significantly increased the AO status, while decreasing lipid and lipid peroxides. The results suggest the necessity of therapeutic co-administration of antioxidants along with conventional drug to such patients. However, due to limited number of cases included in this study, more studies may be required to substantiate the results and arrive at a definitive conclusion, in terms of safety and efficacy of adding an AO therapy in treatment of breast cancer.

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References

  1. American Cancer Society (2007) Breast cancer facts and figures 2005–2006. http://www.cancer.org/docroot/STT/stt/0/2006.asp. cited 13 Mar 2007

  2. Yancik R, Ries LA (2000) Aging and cancer in America. Demographic and epidemiologic perspectives. Hematol Oncol Clin North Am 14:17–23

    Article  PubMed  CAS  Google Scholar 

  3. Parkin DM (1998) The global burden of cancer. Semin Cancer Biol 8:219–235

    Article  PubMed  CAS  Google Scholar 

  4. Gajalakshmi CK, Shanta V, Swaminathan R, Sankaranarayanan R, Black RJ (1997) A population-based survival study on female breast cancer in Madras, India. Br J Cancer 75:771–775

    PubMed  CAS  Google Scholar 

  5. Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82:291–295

    PubMed  CAS  Google Scholar 

  6. Ray G, Batra S, Shukla NK, Deo S, Raina V, Ashok S, Husain SA (2000) Lipid peroxidation, free radical production and antioxidant status in breast cancer. Breast Cancer Res Treat 59:163–170

    Article  PubMed  CAS  Google Scholar 

  7. Vaca CE, Wilhelm J, Harms-Ringdahl M (1988) Interaction of lipid peroxidation products with DNA. A review. Mutat Res 195:137–149

    PubMed  CAS  Google Scholar 

  8. Polat MF, Taysi S, Gul M, Cikman O, Yilmaz I, Bakan E, Erdogan F (2002) Oxidant/antioxidant status in blood of patients with malignant breast tumour and benign breast disease. Cell Biochem Funct 20:327–331

    Article  PubMed  CAS  Google Scholar 

  9. Bakan N, Taysi S, Yilmaz O, Bakan E, Kuskay S, Uzun N, Gundogdu M (2003) Glutathione peroxidase, glutathione reductase, Cu–Zn superoxide dismutase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic lymphocytic leukemia. Clin Chim Acta 338:143–149

    Article  PubMed  CAS  Google Scholar 

  10. Howell A, Osborne CK, Morris C, Wakeling AE (2000) ICI 182,780 (Faslodex): development of a novel, “pure” antiestrogen. Cancer 89:817–825

    Article  PubMed  CAS  Google Scholar 

  11. Adlard JW, Campbell J, Bishop JM, Dodwell DJ (2002) Morbidity of tamoxifen-perceptions of patients and healthcare professionals. Breast 11:335–339

    Article  PubMed  CAS  Google Scholar 

  12. Elefsiniotis IS, Pantazis KD, Ilias A, Pallis L, Mariolis A, Glynou I, Kada H, Moulakakis A (2004) Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance. Eur J Gastroenterol Hepatol 16:593–598

    Article  PubMed  CAS  Google Scholar 

  13. Yuvaraj S, Premkumar VG, Vijayasarathy K, Gangadaran SG, Sachdanandam P (2007) Ameliorating effect of coenzyme Q(10), riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins. Clin Biochem 40:623–628

    Article  PubMed  CAS  Google Scholar 

  14. Lox C, Ronaghan C, Cobos E (1998) Blood chemistry profiles in menopausal women administered tamoxifen for breast cancer. Gen Pharmacol 30:121–124

    PubMed  CAS  Google Scholar 

  15. El-Beshbishy HA (2005) The effect of dimethyl dimethoxy biphenyl dicarboxylate (DDB) against tamoxifen-induced liver injury in rats: DDB use is curative or protective. J Biochem Mol Biol 38:300–306

    PubMed  CAS  Google Scholar 

  16. Da Costa GG, McDaniel-Hamilton LP, Heflich RH, Marques MM, Beland FA (2001) DNA adduct formation and mutant induction in Sprague-Dawley rats treated with tamoxifen and its derivatives. Carcinogenesis 22:1307–1315

    Article  PubMed  CAS  Google Scholar 

  17. Tabassum H, Rehman H, Banerjee BD, Raisuddin S, Parvez S (2001) Attenuation of tamoxifen-induced hepatotoxicity by taurine in mice. Clin Chim Acta 370:129–136

    Article  CAS  Google Scholar 

  18. Nohl H, Gille L, Kozlov AV (1999) Critical aspects of the antioxidant function of coenzyme Q in biomembranes. Biofactors 9:155–161

    PubMed  CAS  Google Scholar 

  19. Yalcin A, Kilinc E, Sagcan A, Kultursay H (2004) Coenzyme Q10 concentrations in coronary artery disease. Clin Biochem 37:706–709

    Article  PubMed  CAS  Google Scholar 

  20. Premkumar VG, Yuvaraj S, Vijayasarathy K, Gangadaran SG, Sachdanandam P (2007) Effect of coenzyme Q10, riboflavin and niacin on serum CEA and CA 15–3 levels in breast cancer patients undergoing tamoxifen therapy. Biol Pharm Bull 30:367–370

    Article  PubMed  CAS  Google Scholar 

  21. Perumal SS, Shanthi P, Sachdanandam P (2005) Augmented efficacy of tamoxifen in rat breast tumorigenesis when gavaged along with riboflavin, niacin, and CoQ10: effects on lipid peroxidation and antioxidants in mitochondria. Chem Biol Interact 152:49–58

    Article  PubMed  CAS  Google Scholar 

  22. Imada Y, Iida H, Ono S, Murahashi S (2003) Flavin catalyzed oxidations of sulfides and amines with molecular oxygen. J Am Chem Soc 125:2868–2869

    Article  PubMed  CAS  Google Scholar 

  23. Ganji SH, Kamanna VS, Kashyap ML (2003) Niacin and cholesterol: role in cardiovascular disease (review). J Nutr Biochem 14:298–305

    Article  PubMed  CAS  Google Scholar 

  24. Yagi K (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15:212–216

    Article  PubMed  CAS  Google Scholar 

  25. Rouser G, Fkeischer S, Yamamoto A (1970) Two dimensional thin layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids 5:494–496

    Article  PubMed  CAS  Google Scholar 

  26. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  PubMed  CAS  Google Scholar 

  27. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  PubMed  CAS  Google Scholar 

  28. Habig WH, Jakoby WB (1981) Assays for differentiation of glutathione S-transferases. Methods Enzymol 77:398–405

    PubMed  CAS  Google Scholar 

  29. Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    PubMed  CAS  Google Scholar 

  30. Omaye ST, Turnbull JD, Sauberlich HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 62:3–11

    Article  PubMed  CAS  Google Scholar 

  31. Hansen LG, Warwick WJ (1969) A fluorometric micromethod for serum vitamins A and E. Tech Bull Regist Med Technol 39:70–73

    PubMed  CAS  Google Scholar 

  32. Baker H, Frank O, De Angelis B, Feingold S (1989) Plasma tocopherol in man at various times after ingesting free or acetylated tocopherol. Nutr Rep Int 21:531–536

    Google Scholar 

  33. Darbkin DL, Austin JM (1932) Spectrophotometric studies, spectrophotometric constants for common haemoglobin derivatives in human, dog and rabbit blood. J Biol Chem 98:719–733

    Google Scholar 

  34. Ray G, Husain SA (2001) Role of lipids, lipoproteins and vitamins in women with breast cancer. Clin Biochem 34:71–76

    Article  PubMed  CAS  Google Scholar 

  35. Summerfield FW, Tappel AL (1983) Determination by fluorescence quenching of the environment of DNA crosslinks made by malondialdehyde. Biochim Biophys Acta 740:185–189

    PubMed  CAS  Google Scholar 

  36. Szepsenwol J (1966) Carcinogenic effect of cholesterol in mice. Proc Soc Exp Biol Med 21:168–171

    Google Scholar 

  37. Babu JR, Sundravel S, Arumugam G, Renuka R, Deepa N, Sachdanandam P (2000) Salubrious effect of vitamin C and vitamin E on tamoxifen-treated women in breast cancer with reference to plasma lipid and lipoprotein levels. Cancer Lett 151:1–5

    Article  PubMed  CAS  Google Scholar 

  38. Takatani O, Okumoto T, Kosano H (1991) Genesis of breast cancer in Japanese: a possible relationship between sex hormone binding globulin (SHBG) and serum lipid components. Breast Cancer Res Treat 18(Suppl 1):S27–S29

    Article  PubMed  Google Scholar 

  39. Premkumar VG, Yuvaraj S, Vijayasarathy K, Gangadaran SG, Sachdanandam P (2007) Serum cytokine levels of interleukin-1beta, -6, -8, tumour necrosis factor-alpha and vascular endothelial growth factor in breast cancer patients treated with Tamoxifen and supplemented with Co-enzyme Q(10), Riboflavin and Niacin. Basic Clin Pharmacol Toxicol 100:387–391

    Article  PubMed  CAS  Google Scholar 

  40. Jablonska E, Kiluk M, Markiewicz W, Piotrowski L, Grabowska Z, Jablonski J (2001) TNF-α, IL-6 and their soluble receptor serum levels and secretion by neutrophils in cancer patients. Arch Immunol Ther Exp 49:63–69

    CAS  Google Scholar 

  41. Zhao SP, Wu J (2004) Fenofibrate reduces tumor necrosis factor-alpha serum concentration and adipocyte secretion of hypercholesterolemic rabbits. Clin Chim Acta 347:145–150

    Article  PubMed  CAS  Google Scholar 

  42. James AM, Smith RA, Murphy MP (2004) Antioxidant and prooxidant properties of mitochondrial Coenzyme Q. Arch Biochem Biophys 423:47–56

    Article  PubMed  CAS  Google Scholar 

  43. Kagan V, Serbinova E, Packer L (1990) Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 169:851–857

    Article  PubMed  CAS  Google Scholar 

  44. Powers HJ (1999) Current knowledge concerning optimum nutritional status of riboflavin, niacin and pyridoxine. Proc Nutr Soc 58:435–440

    Article  PubMed  CAS  Google Scholar 

  45. Jin FY, Kamanna VS, Kashyap ML (1999) Niacin accelerates intracellular ApoB degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (HepG2) cells. Arterioscler Thromb Vasc Biol 19:1051–1059

    PubMed  CAS  Google Scholar 

  46. Ferlini C, Scambia G, Marone M, Distefano M, Gaggini C, Ferrandina G, Fattorossi A, Isola G, Benedetti Panici P, Mancuso S (1999) Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell lines. Br J Cancer 79:257–263

    PubMed  CAS  Google Scholar 

  47. Nazarewicz RR, Zenebe WJ, Parihar A, Larson SK, Alidema E, Choi J, Ghafourifar P (2007) Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase. Cancer Res 67:1282–1290

    Article  PubMed  CAS  Google Scholar 

  48. Yeh CC, Hou MF, Tsai SM, Lin SK, Hsiao JK, Huang JC, Wang LH, Wu SH, Hou LA, Ma H, Tsai LY (2005) Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer. Clin Chim Acta 361:104–111

    Article  PubMed  CAS  Google Scholar 

  49. Buzby GP, Mullen JL, Stein TP, Miller EE, Hobbs CL, Rosato EF (1980) Host–tumor interaction and nutrient supply. Cancer 45:2940–2948

    Article  PubMed  CAS  Google Scholar 

  50. Simeone AM, Ekmekcioglu S, Broemeling LD, Grimm EA, Tari AM (2002) A novel mechanism by which N-(4-hydroxyphenyl)retinamide inhibits breast cancer cell growth: the production of nitric oxide. Mol Cancer Ther 1:1009–1017

    PubMed  CAS  Google Scholar 

  51. Michiels C, Raes M, Toussaint O, Remacle J (1994) Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 17:235–248

    Article  PubMed  CAS  Google Scholar 

  52. Yan Q, Briehl M, Crowley CL, Payne CM, Bernstein H, Bernstein C (1999) The NAD+ precursors, nicotinic acid and nicotinamide upregulate glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase mRNA in Jurkat cells. Biochem Biophys Res Commun 255:133–136

    Article  PubMed  CAS  Google Scholar 

  53. Lee CK, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R, Prolla TA (2004) The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice. Free Radic Biol Med 36:1043–1057

    Article  PubMed  CAS  Google Scholar 

  54. Fernandez-Ayala DJ, Lopez-Lluch G, Garcia-Valdes M, Arroyo A, Navas P (2005) Specificity of coenzyme Q10 for a balanced function of respiratory chain and endogenous ubiquinone biosynthesis in human cells. Biochim Biophys Acta 1706:174–183

    Article  PubMed  CAS  Google Scholar 

  55. Abiaka C, Al-Awadi F, Al-Sayer H, Gulshan S, Behbehani A, Farghally M (2002) Activities of erythrocyte antioxidant enzymes in cancer patients. J Clin Lab Anal 16:167–171

    Article  PubMed  CAS  Google Scholar 

  56. Khanzode SS, Muddeshwar MG, Khanzode SD, Dakhale GN (2004) Antioxidant enzymes and lipid peroxidation in different stages of breast cancer. Free Radic Res 38:81–85

    Article  PubMed  CAS  Google Scholar 

  57. Saygili EI, Akcay T, Konukoglu D, Papilla C (2003) Glutathione and glutathione-related enzymes in colorectal cancer patients. J Toxicol Environ Health 66:411–415

    Article  CAS  Google Scholar 

  58. Fang YZ, Yang S, Wu G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18:872–879

    Article  PubMed  CAS  Google Scholar 

  59. Crane FL (2001) Biochemical functions of coenzyme Q10. J Am Coll Nutr 20:591–598

    PubMed  CAS  Google Scholar 

  60. Kamat JP, Devasagayam TP (1996) Methylene blue plus light-induced lipid peroxidation in rat liver microsomes: inhibition by nicotinamide (vitamin B3) and other antioxidants. Chem Biol Interact 99:1–16

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

The authors whole-heartedly thank Kaneka Corp., Japan for their philanthropic gift of Coenzyme Q10 samples and Madras Pharmaceuticals, Chennai, India for Niacin and Riboflavin samples. The technical expertise provided by Dr. P. Shiva Kumar, Dr. Sarapaul, Mr. Neelamohan of Kumaran Hospital, Chennai and Mr. S. Sasi Kumar and Dr. D. Dakshayani and Dr. V. Jaganathan of Billroth Hospital, Chennai are greatly acknowledged.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Dr. ALMP-GIBMS, University of Madras, Taramani Campus, Chennai, 600 113, Tamil Nadu, India

    Srinivasan Yuvaraj, Vummidi Giridhar Premkumar & Panchanatham Sachdanandam

  2. Department of Medical Oncology, Government Royapettah Hospital, Kilpauk Medical College, Chennai, 600 014, Tamil Nadu, India

    Kothandaraman Vijayasarathy & Sitthu Govindaswamy Dinakaran Gangadaran

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  1. Srinivasan Yuvaraj
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  3. Kothandaraman Vijayasarathy
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  5. Panchanatham Sachdanandam
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Correspondence to Panchanatham Sachdanandam.

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Yuvaraj, S., Premkumar, V.G., Vijayasarathy, K. et al. Augmented antioxidant status in Tamoxifen treated postmenopausal women with breast cancer on co-administration with Coenzyme Q10, Niacin and Riboflavin. Cancer Chemother Pharmacol 61, 933–941 (2008). https://doi.org/10.1007/s00280-007-0547-z

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