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N-Acetylcysteine for Reduction of Oxidative Stress/Damage and Prevention of Melanoma

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Bioactive Dietary Factors and Plant Extracts in Dermatology

Part of the book series: Nutrition and Health ((NH))

Abstract

N-acetyl-l-cysteine is a potent antioxidant that is commercially available as an over-the-counter supplement that has demonstrated efficacy for several medical applications.

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Abbreviations

8-OH-dG:

8-Hydroxy-2′-deoxyguanine

Cys:

Cysteine

GGTase:

Gamma-glutamyl transferase

GR:

Glutathione reductase

GSH:

Glutathione

GSSG:

Glutathione disulfide

GST:

Glutathione S-transferase

NAC:

N-Acetylcysteine

NADPH:

Nicotinamide adenine dinucleotide phosphate reduced form

NAPQI:

N-Acetyl-p-quinonimine

Protein-SG:

Protein-glutathione mixed disulfide

ROS:

Reactive oxygen species

UV:

Ultraviolet radiation

γ(gamma)-GCS:

Gamma-glutamylcysteine synthase

References

  1. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489–92.

    PubMed  CAS  Google Scholar 

  2. Meister A, Anderson ME. Glutathione. Annu Rev Biochem. 1983;52:711–60.

    Article  PubMed  CAS  Google Scholar 

  3. Hoek KS, Schlegel NC, Eichhoff OM, et al. Novel MITF targets identified using a two-step DNA microarray strategy. Pigment Cell Melanoma Res. 2008;21(6):665–76.

    Article  PubMed  CAS  Google Scholar 

  4. Chintala S, Li W, Lamoreux ML, et al. Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells. Proc Natl Acad Sci U S A. 2005;102(31):10964–9.

    Article  PubMed  CAS  Google Scholar 

  5. Zhang H, Forman HJ. Redox regulation of gamma-glutamyl transpeptidase. Am J Respir Cell Mol Biol. 2009;41(5):509–15.

    Article  PubMed  CAS  Google Scholar 

  6. Lu SC. Regulation of glutathione synthesis. Mol Aspects Med. 2009;30(1–2):42–59.

    Article  PubMed  CAS  Google Scholar 

  7. Cotter MA, Thomas J, Cassidy P, et al. N-acetylcysteine protects melanocytes against oxidative stress/damage and delays onset of ultraviolet-induced melanoma in mice. Clin Cancer Res. 2007;13(19):5952–8.

    Article  PubMed  CAS  Google Scholar 

  8. Haywood R, Andrady C, Kassouf N, Sheppard N. Intensity-dependent direct solar radiation- and UVA-induced radical damage to human skin and DNA, lipids and proteins. Photochem Photobiol. 2011;87(1):117–30.

    Article  PubMed  CAS  Google Scholar 

  9. Goodson AG, Cotter MA, Cassidy P, et al. Use of oral N-acetylcysteine for protection of melanocytic nevi against UV-induced oxidative stress: towards a novel paradigm for melanoma chemoprevention. Clin Cancer Res. 2009;15(23):7434–40.

    Article  PubMed  CAS  Google Scholar 

  10. Brigelius-Flohe R, Wingler K, Muller C. Estimation of individual types of glutathione peroxidases. Methods Enzymol. 2002;347:101–12.

    Article  PubMed  CAS  Google Scholar 

  11. Lu SC. Regulation of hepatic glutathione synthesis: current concepts and controversies. FASEB J. 1999;13(10): 1169–83.

    PubMed  CAS  Google Scholar 

  12. Kane RE, Li AP, Kaminski DR. Sulfation and glucuronidation of acetaminophen by human hepatocytes cultured on Matrigel and type 1 collagen reproduces conjugation in vivo. Drug Metab Dispos. 1995;23(3):303–7.

    PubMed  CAS  Google Scholar 

  13. Ferner RE, Dear JW, Bateman DN. Management of paracetamol poisoning. BMJ. 2011;342:d2218.

    Article  PubMed  Google Scholar 

  14. Schaefer JD. Acetadote. Physician’s Desk Reference. 2011;65:986–989.

    Google Scholar 

  15. Meyskens Jr FL, Farmer P, Fruehauf JP. Redox regulation in human melanocytes and melanoma. Pigment Cell Res. 2001;14(3):148–54.

    Article  PubMed  CAS  Google Scholar 

  16. Wittgen HG, van Kempen LC. Reactive oxygen species in melanoma and its therapeutic implications. Melanoma Res. 2007;17(6):400–9.

    Article  PubMed  CAS  Google Scholar 

  17. Wood SR, Berwick M, Ley RD, Walter RB, Setlow RB, Timmins GS. UV causation of melanoma in xiphophorus is dominated by melanin photosensitized oxidant production. Proc Natl Acad Sci U S A. 2006;103(11):4111–5.

    Article  PubMed  CAS  Google Scholar 

  18. de Souza GA, Godoy LM, Teixeira VR, et al. Proteomic and SAGE profiling of murine melanoma progression indicates the reduction of proteins responsible for ROS degradation. Proteomics. 2006;6(5):1460–70.

    Article  PubMed  Google Scholar 

  19. Grammatico P, Maresca V, Roccella F, et al. Increased sensitivity to peroxidizing agents is correlated with an imbalance of antioxidants in normal melanocytes from melanoma patients. Exp Dermatol. 1998;7(4):205–12.

    Article  PubMed  CAS  Google Scholar 

  20. Pavel S, van Nieuwpoort F, van der Meulen H, et al. Disturbed melanin synthesis and chronic oxidative stress in dysplastic naevi. Eur J Cancer. 2004;40(9):1423–30.

    Article  PubMed  CAS  Google Scholar 

  21. Streutker CJ, McCready D, Jimbow K, From L. Malignant melanoma in a patient with oculocutaneous albinism. J Cutan Med Surg. 2000;4(3):149–52.

    PubMed  CAS  Google Scholar 

  22. Riley PA. Melanin. Int J Biochem Cell Biol. 1997;29(11):1235–9.

    Article  PubMed  CAS  Google Scholar 

  23. Jenkins NC, Liu T, Cassidy P, et al. The p16(INK4A) tumor suppressor regulates cellular oxidative stress. Oncogene. 2011;30(3):265–74.

    Article  PubMed  CAS  Google Scholar 

  24. Urabe K, Aroca P, Tsukamoto K, et al. The inherent cytotoxicity of melanin precursors: a revision. Biochim Biophys Acta. 1994;1221(3):272–8.

    Article  PubMed  CAS  Google Scholar 

  25. Farmer PJ, Gidanian S, Shahandeh B, Di Bilio AJ, Tohidian N, Meyskens Jr FL. Melanin as a target for melanoma chemotherapy: pro-oxidant effect of oxygen and metals on melanoma viability. Pigment Cell Res. 2003;16(3):273–9.

    Article  PubMed  CAS  Google Scholar 

  26. Bruner SD, Norman DP, Verdine GL. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature. 2000;403(6772):859–66.

    Article  PubMed  CAS  Google Scholar 

  27. Pashaei S, Li L, Zhang H, et al. Concordant loss of heterozygosity of DNA repair gene, hOGG1, in melanoma in situ and atypical melanocytic hyperplasia. J Cutan Pathol. 2008;35(6):525–31.

    Article  PubMed  Google Scholar 

  28. Pleasance ED, Cheetham RK, Stephens PJ, et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature. 2010;463(7278):191–6.

    Article  PubMed  CAS  Google Scholar 

  29. Pho L, Grossman D, Leachman SA. Melanoma genetics: a review of genetic factors and clinical phenotypes in familial melanoma. Curr Opin Oncol. 2006;18(2):173–9.

    Article  PubMed  CAS  Google Scholar 

  30. Fargnoli MC, Gandini S, Peris K, Maisonneuve P, Raimondi S. MC1R variants increase melanoma risk in families with CDKN2A mutations: a meta-analysis. Eur J Cancer. 2010;46(8):1413–20.

    Article  PubMed  CAS  Google Scholar 

  31. Abdel-Malek ZA, Kadekaro AL, Swope VB. Stepping up melanocytes to the challenge of UV exposure. Pigment Cell Melanoma Res. 2010;23(2):171–86.

    Article  PubMed  CAS  Google Scholar 

  32. Kadekaro AL, Leachman S, Kavanagh RJ, et al. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. FASEB J. 2010;24(10):3850–60.

    Article  PubMed  CAS  Google Scholar 

  33. Song X, Mosby N, Yang J, Xu A, Abdel-Malek Z, Kadekaro AL. alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes. Pigment Cell Melanoma Res. 2009;22(6): 809–18.

    Article  PubMed  CAS  Google Scholar 

  34. Kokot A, Metze D, Mouchet N, et al. Alpha-melanocyte-stimulating hormone counteracts the suppressive effect of UVB on Nrf2 and Nrf-dependent gene expression in human skin. Endocrinology. 2009;150(7):3197–206.

    Article  PubMed  CAS  Google Scholar 

  35. Herraiz C, Journe F, Abdel-Malek Z, Ghanem G, Jimenez-Cervantes C, Garcia-Borron JC. Signaling from the human melanocortin 1 receptor to ERK1 and ERK2 mitogen-activated protein kinases involves transactivation of cKIT. Mol Endocrinol. 2011;25(1):138–56.

    Article  PubMed  CAS  Google Scholar 

  36. Kennedy C, ter Huurne J, Berkhout M, et al. Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Invest Dermatol. 2001;117(2):294–300.

    Article  PubMed  CAS  Google Scholar 

  37. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297(8):842–57.

    Article  PubMed  CAS  Google Scholar 

  38. Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial. J Natl Cancer Inst. 1996;88(21):1550–9.

    Article  PubMed  CAS  Google Scholar 

  39. Hercberg S, Ezzedine K, Guinot C, et al. Antioxidant supplementation increases the risk of skin cancers in women but not in men. J Nutr. 2007;137(9):2098–105.

    PubMed  CAS  Google Scholar 

  40. D’Agostini F, Balansky RM, Camoirano A, De Flora S. Modulation of light-induced skin tumors by N-acetylcysteine and/or ascorbic acid in hairless mice. Carcinogenesis. 2005;26(3):657–64.

    Article  PubMed  Google Scholar 

  41. Thomas J, Liu T, Cotter MA, et al. Melanocyte expression of survivin promotes development and metastasis of UV-induced melanoma in HGF-transgenic mice. Cancer Res. 2007;67(11):5172–8.

    Article  PubMed  CAS  Google Scholar 

  42. Noonan FP, Dudek J, Merlino G, De Fabo EC. Animal models of melanoma: an HGF/SF transgenic mouse model may facilitate experimental access to UV initiating events. Pigment Cell Res. 2003;16(1):16–25.

    Article  PubMed  CAS  Google Scholar 

  43. Kang S, Chung JH, Lee JH, et al. Topical N-acetyl cysteine and genistein prevent ultraviolet-light-induced signaling that leads to photoaging in human skin in vivo. J Invest Dermatol. 2003;120(5):835–41.

    Article  PubMed  CAS  Google Scholar 

  44. Kaur P, Kaur G, Bansal MP. Upregulation of AP1 by tertiary butyl hydroperoxide induced oxidative stress and subsequent effect on spermatogenesis in mice testis. Mol Cell Biochem. 2008;308(1–2):177–81.

    Article  PubMed  CAS  Google Scholar 

  45. Fisher GJ, Wang ZQ, Datta SC, Varani J, Kang S, Voorhees JJ. Pathophysiology of premature skin aging induced by ultraviolet light. N Eng J Med. 1997;337(20):1419–28.

    Article  CAS  Google Scholar 

  46. Marrot L, Jones C, Perez P, Meunier JR. The significance of Nrf2 pathway in (photo)-oxidative stress response in melanocytes and keratinocytes of the human epidermis. Pigment Cell Melanoma Res. 2008;21(1):79–88.

    Article  PubMed  CAS  Google Scholar 

  47. Wuyts WA, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE, Demedts MG, Verleden GM. N-acetylcysteine inhibits interleukin-17-induced interleukin-8 production from human airway smooth muscle cells: a possible role for anti-oxidative treatment in chronic lung rejection? J Heart Lung Transplant. 2004;23(1):122–7.

    Article  PubMed  Google Scholar 

  48. Trivedi H, Daram S, Szabo A, Bartorelli AL, Marenzi G. High-dose N-acetylcysteine for the prevention of contrast-induced nephropathy. Am J Med. 2009;122(9):874 e9–15.

    Article  Google Scholar 

  49. Suwannaroj S, Lagoo A, Keisler D, McMurray RW. Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE). Lupus. 2001;10(4):258–65.

    Article  PubMed  CAS  Google Scholar 

  50. Kudaravalli J. Improvement in endothelial dysfunction in patients with systemic lupus erythematosus with N-acetylcysteine and atorvastatin. Indian J Pharmacol. 2011;43(3):311–5.

    Article  PubMed  CAS  Google Scholar 

  51. Vasu VT, de Cruz SJ, Houghton JS, et al. Evaluation of thiol-based antioxidant therapeutics in cystic fibrosis sputum: focus on myeloperoxidase. Free Radic Res. 2011;45(2):165–76.

    Article  PubMed  CAS  Google Scholar 

  52. Varelogianni G, Oliynyk I, Roomans GM, Johannesson M. The effect of N-acetylcysteine on chloride efflux from airway epithelial cells. Cell Biol Int. 2010;34(3):245–52.

    Article  PubMed  CAS  Google Scholar 

  53. Dauletbaev N, Fischer P, Aulbach B, et al. A phase II study on safety and efficacy of high-dose N-acetylcysteine in patients with cystic fibrosis. Eur J Med Res. 2009;14(8):352–8.

    PubMed  CAS  Google Scholar 

  54. Shahin AY, Hassanin IM, Ismail AM, Kruessel JS, Hirchenhain J. Effect of oral N-acetyl cysteine on recurrent preterm labor following treatment for bacterial vaginosis. Int J Gynaecol Obstet. 2009;104(1):44–8.

    Article  PubMed  CAS  Google Scholar 

  55. Murphy KT, Medved I, Brown MJ, Cameron-Smith D, McKenna MJ. Antioxidant treatment with N-acetylcysteine regulates mammalian skeletal muscle Na  +  -K  +  -ATPase alpha gene expression during repeated contractions. Exp Physiol. 2008;93(12):1239–48.

    Article  PubMed  CAS  Google Scholar 

  56. Kelly MK, Wicker RJ, Barstow TJ, Harms CA. Effects of N-acetylcysteine on respiratory muscle fatigue during heavy exercise. Respir Physiol Neurobiol. 2009;165(1):67–72.

    Article  PubMed  CAS  Google Scholar 

  57. Redondo P, Bauza A. Topical N-acetylcysteine for lamellar ichthyosis. Lancet. 1999;354(9193):1880.

    Article  PubMed  CAS  Google Scholar 

  58. Dean OM, van den Buuse M, Berk M, Copolov DL, Mavros C, Bush AI. N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: relevance to schizophrenia and bipolar disorder. Neurosci Lett. 2011;499(3):149–53.

    Article  PubMed  CAS  Google Scholar 

  59. Sansone RA, Sansone LA. Getting a knack for NAC: N-Acetyl-Cysteine. Innov Clin Neurosci. 2011;8(1):10–4.

    Google Scholar 

  60. Odlaug BL, Grant JE. N-acetyl cysteine in the treatment of grooming disorders. J Clin Psychopharmacol. 2007;27(2):227–9.

    Article  PubMed  Google Scholar 

  61. Gray KM, Watson NL, Carpenter MJ, Larowe SD. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. Am J Addict. 2010;19(2):187–9.

    Article  PubMed  Google Scholar 

  62. Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ. An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(2): 389–94.

    Article  PubMed  CAS  Google Scholar 

  63. Knackstedt LA, LaRowe S, Mardikian P, et al. The role of cystine-glutamate exchange in nicotine dependence in rats and humans. Biol Psychiatry. 2009;65(10):841–5.

    Article  PubMed  CAS  Google Scholar 

  64. Berk M, Copolov D, Dean O, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia—a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008;64(5):361–8.

    Article  PubMed  CAS  Google Scholar 

  65. Berk M, Copolov DL, Dean O, et al. N-acetyl cysteine for depressive symptoms in bipolar disorder—a double-blind randomized placebo-controlled trial. Biol Psychiatry. 2008;64(6):468–75.

    Article  PubMed  CAS  Google Scholar 

  66. Adair JC, Knoefel JE, Morgan N. Controlled trial of N-acetylcysteine for patients with probable Alzheimer’s disease. Neurology. 2001;57(8):1515–7.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA

    Pamela B. Cassidy

  2. Department of Dermatology, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA

    Sancy A. Leachman

  3. Department of Dermatology, University of Utah Health Sciences Center, Oncological Sciences at the University of Utah, 30 North 1900 East, Salt Lake City, UT, 84132, USA

    Douglas Grossman M.D., Ph.D.

Authors
  1. Pamela B. Cassidy
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  2. Sancy A. Leachman
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  3. Douglas Grossman M.D., Ph.D.
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Correspondence to Douglas Grossman M.D., Ph.D. .

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Editors and Affiliations

  1. University of Arizona Mel and, Enid Zuckerman College of Public Health, Division of Health Promotion Sciences, University of Arizona School of Medicine, Tuscon, 85724, Arizona, USA

    Ronald Ross Watson

  2. Division of Health Promotion Sciences, Mel and Enid Zuckerman, University of Arizona, 1295 N. Martin Avenue, Tucson, 85724, Arizona, USA

    Sherma Zibadi

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Cassidy, P.B., Leachman, S.A., Grossman, D. (2013). N-Acetylcysteine for Reduction of Oxidative Stress/Damage and Prevention of Melanoma. In: Watson, R., Zibadi, S. (eds) Bioactive Dietary Factors and Plant Extracts in Dermatology. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-167-7_31

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  • DOI: https://doi.org/10.1007/978-1-62703-167-7_31

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