Tumor Biology

, Volume 35, Issue 9, pp 8359–8368 | Cite as

Running for time: circadian rhythms and melanoma

  • Elitza P. Markova-CarEmail author
  • Davor Jurišić
  • Nataša Ilić
  • Sandra Kraljević Pavelić


Circadian timing system includes an input pathway transmitting environmental signals to a core oscillator that generates circadian signals responsible for the peripheral physiological or behavioural events. Circadian 24-h rhythms regulate diverse physiologic processes. Deregulation of these rhythms is associated with a number of pathogenic conditions including depression, diabetes, metabolic syndrome and cancer. Melanoma is a less common type of skin cancer yet more aggressive often with a lethal ending. However, little is known about circadian control in melanoma and exact functional associations between core clock genes and development of melanoma skin cancer. This paper, therefore, comprehensively analyses current literature data on the involvement of circadian clock components in melanoma development. In particular, the role of circadian rhythm deregulation is discussed in the context of DNA repair mechanisms and influence of UV radiation and artificial light exposure on cancer development. The role of arylalkylamine N-acetyltransferase (AANAT) enzyme and impact of melatonin, as a major output factor of circadian rhythm, and its protective role in melanoma are discussed in details. We hypothesise that further understanding of clock genes’ involvement and circadian regulation might foster discoveries in the field of melanoma diagnostics and treatment.


Clock genes Circadian rhythm Melatonin Cancer Melanoma 



This work was supported by the Croatian Ministry of Science, Education and Sports grant (335-0000000-3532).

Conflicts of interest


Supplementary material

13277_2014_1904_MOESM1_ESM.pdf (247 kb)
Online Resource 1 Melanoma - clinical data review (PDF 247 kb)


  1. 1.
    Rivkees S. Circadian rhythms—genetic regulation and clinical disorders. Growth Genet Horm. 2002;18:1–6.Google Scholar
  2. 2.
    Inouye ST, Kawamura H. Persistence of circadian rhythmicity in a mammalian hypothalamic ‘island’ containing the suprachiasmatic nucleus. Proc Natl Acad Sci U S A. 1979;76:5962–6.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Klein DC, Moore RY, Reppert SM. Suprachiasmatic nucleus: the mind’s clock. New York: Oxford University Press; 1991.Google Scholar
  4. 4.
    Markova EP, Ueda H, Sakamoto K, Oishi K, Shimada T, Takeda M. Cloning of Cyc (Bmal1) homolog in Bombyx mori: structural analysis and tissue specific distributions. Comp Biochem Physiol B Biochem Mol Biol. 2003;134:535–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Oishi K, Sakamoto K, Okada T, Nagase T, Ishida N. Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats. Biochem Biophys Res Commun. 1998;253:199–203.PubMedCrossRefGoogle Scholar
  6. 6.
    Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature. 2002;418:935–41.PubMedCrossRefGoogle Scholar
  7. 7.
    Dibner C, Schibler U, Albrecht U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol. 2010;72:517–49.PubMedCrossRefGoogle Scholar
  8. 8.
    Yu EA, Weaver DR. Disrupting the circadian clock: gene-specific effects on aging, cancer, and other phenotypes. Aging. 2011;3:479–93.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Lengyel Z, Lovig C, Kommedal S, Keszthelyi R, Szekeres G, Battyáni Z, et al. Altered expression patterns of clock gene mRNAs and clock proteins in human skin tumors. Tumour Biol. 2013;34:811–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Relles D, Sendecki J, Chipitsyna G, Hyslop T, Yeo CJ, Arafat HA. Circadian gene expression and clinicopathologic correlates in pancreatic cancer. J Gastrointest Surg. 2013;17:443–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Hsu C-M, Lin S-F, Lu C-T, Lin P-M, Yang M-Y. Altered expression of circadian clock genes in head and neck squamous cell carcinoma. Tumour Biol. 2012;33:149–55.PubMedCrossRefGoogle Scholar
  12. 12.
    Mazzoccoli G, Panza A, Valvano MR, Palumbo O, Carella M, Pazienza V, et al. Clock gene expression levels and relationship with clinical and pathological features in colorectal cancer patients. Chronobiol Int. 2011;28:841–51.PubMedCrossRefGoogle Scholar
  13. 13.
    Oshima T, Takenoshita S, Akaike M, Kunisaki C, Fujii S, Nozaki A, et al. Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer. Oncol Rep. 2011;25:1439–46.PubMedCrossRefGoogle Scholar
  14. 14.
    Mostafaie N, Kállay E, Sauerzapf E, Bonner E, Kriwanek S, Cross HS, et al. Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer. Mol Carcinog. 2009;48:642–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Alhopuro P, Björklund M, Sammalkorpi H, Turunen M, Tuupanen S, Biström M, et al. Mutations in the circadian gene CLOCK in colorectal cancer. Mol Cancer Res. 2010;8:952–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Gery S, Komatsu N, Kawamata N, Miller CW, Desmond J, Virk RK, et al. Epigenetic silencing of the candidate tumor suppressor gene Per1 in non-small cell lung cancer. Clin Cancer Res. 2007;13:1399–404.PubMedCrossRefGoogle Scholar
  17. 17.
    Yoshida K, Sato M, Hase T, Elshazley M, Yamashita R, Usami N, et al. TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival. Cancer Sci. 2013;104:171–7.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Chen S-T, Choo K-B, Hou M-F, Yeh K-T, Kuo S-J, Chang J-G. Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers. Carcinogenesis. 2005;26:1241–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Hoffman AE, Zheng T, Yi C-H, Stevens RG, Ba Y, Zhang Y, et al. The core circadian gene Cryptochrome 2 influences breast cancer risk, possibly by mediating hormone signaling. Cancer Prev Res (Phila). 2010;3:539–48.CrossRefGoogle Scholar
  20. 20.
    Hoffman AE, Yi C-H, Zheng T, Stevens RG, Leaderer D, Zhang Y, et al. CLOCK in breast tumorigenesis: genetic, epigenetic, and transcriptional profiling analyses. Cancer Res. 2010;70:1459–68.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Winter SL, Bosnoyan-Collins L, Pinnaduwage D, Andrulis IL. Expression of the circadian clock genes Per1 and Per2 in sporadic and familial breast tumors. Neoplasia. 2007;9:797–800.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Hoffman AE, Zheng T, Ba Y, Zhu Y. The circadian gene NPAS2, a putative tumor suppressor, is involved in DNA damage response. Mol Cancer Res. 2008;6:1461–8.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Yeh K-T, Yang M-Y, Liu T-C, Chen J-C, Chan W-L, Lin S-F, et al. Abnormal expression of period 1 (PER1) in endometrial carcinoma. J Pathol. 2005;206:111–20.PubMedCrossRefGoogle Scholar
  24. 24.
    Cao Q, Gery S, Dashti A, Yin D, Zhou Y, Gu J, et al. A role for the clock gene per1 in prostate cancer. Cancer Res. 2009;69:7619–25.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Taniguchi H, Fernández AF, Setién F, Ropero S, Ballestar E, Villanueva A, et al. Epigenetic inactivation of the circadian clock gene BMAL1 in hematologic malignancies. Cancer Res. 2009;69:8447–54.PubMedCrossRefGoogle Scholar
  26. 26.
    Yang M-Y, Chang J-G, Lin P-M, Tang K-P, Chen Y-H, Lin HY-H, et al. Downregulation of circadian clock genes in chronic myeloid leukemia: alternative methylation pattern of hPER3. Cancer Sci. 2006;97:1298–307.PubMedCrossRefGoogle Scholar
  27. 27.
    Gery S, Gombart AF, Yi WS, Koeffler C, Hofmann W-K, Koeffler HP. Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia. Blood. 2005;106:2827–36.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Xia H, Niu Z, Ma H, Cao S, Hao S, Liu Z, et al. Deregulated expression of the Per1 and Per2 in human gliomas. Can J Neurol Sci. 2010;37:365–70.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhao N, Yang K, Yang G, Chen D, Tang H, Zhao D, et al. Aberrant expression of clock gene period1 and its correlations with the growth, proliferation and metastasis of buccal squamous cell carcinoma. PLoS One. 2013;8:e55894.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Fu L, Pelicano H, Liu J, Huang P, Lee C. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell. 2002;111:41–50.PubMedCrossRefGoogle Scholar
  31. 31.
    Wu Y-H, Fischer DF, Kalsbeek A, Garidou-Boof M-L, van der Vliet J, van Heijningen C, et al. Pineal clock gene oscillation is disturbed in Alzheimer’s disease, due to functional disconnection from the ‘master clock’. FASEB J. 2006;20:1874–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Lavebratt C, Sjöholm LK, Soronen P, Paunio T, Vawter MP, Bunney WE, et al. CRY2 is associated with depression. PLoS One. 2010;5:e9407.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Shimba S, Ogawa T, Hitosugi S, Ichihashi Y, Nakadaira Y, Kobayashi M, et al. Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation. PLoS One. 2011;6:e25231.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Gossan N, Zeef L, Hensman J, Hughes A, Bateman JF, Rowley L, et al. The circadian clock in murine chondrocytes regulates genes controlling key aspects of cartilage homeostasis. Arthritis Rheum. 2013;65:2334–45.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Lengyel Z, Battyáni Z, Szekeres G, Csernus V, Nagy AD. Circadian clocks and tumor biology: what is to learn from human skin biopsies? Gen Comp Endocrinol. 2013;188:67–74.PubMedCrossRefGoogle Scholar
  36. 36.
    WHO (2014) Cancer. Accessed Aug 2013.
  37. 37.
    Kraljevic Pavelic S, Sedic M, Bosnjak H, Spaventi S, Pavelic K. Metastasis: new perspectives on an old problem. Mol Cancer. 2011;10:22.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.PubMedCrossRefGoogle Scholar
  39. 39.
    Antoch MP, Kondratov RV, Takahashi JS. Circadian clock genes as modulators of sensitivity to genotoxic stress. Cell Cycle. 2005;4:901–7.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Dronca RS, Leontovich AA, Nevala WK, Markovic SN. Personalized therapy for metastatic melanoma: could timing be everything? Future Oncol. 2012;8:1401–6.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Scheiermann C, Kunisaki Y, Frenette PS. Circadian control of the immune system. Nat Rev Immunol. 2013;13:190–8.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Hua H, Wang Y, Wan C, Liu Y, Zhu B, Wang X, et al. Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice. Cancer Gene Ther. 2007;14:815–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Miyazaki K, Wakabayashi M, Hara Y, Ishida N. Tumor growth suppression in vivo by overexpression of the circadian component, PER2. Genes Cells. 2010;15:351–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Im J-S, Jung B-H, Kim S-E, Lee K-H, Lee J-K. Per3, a circadian gene, is required for Chk2 activation in human cells. FEBS Lett. 2010;584:4731–4.PubMedCrossRefGoogle Scholar
  45. 45.
    Sancar A, Lindsey-Boltz LA, Kang T-H, Reardon JT, Lee JH, Ozturk N. Circadian clock control of the cellular response to DNA damage. FEBS Lett. 2010;584:2618–25.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Shearman LP, Sriram S, Weaver DR, Maywood ES, Chaves I, Zheng B, et al. Interacting molecular loops in the mammalian circadian clock. Science. 2000;288:1013–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, et al. Role of the CLOCK protein in the mammalian circadian mechanism. Science. 1998;280:1564–9.PubMedCrossRefGoogle Scholar
  48. 48.
    DeBruyne JP, Weaver DR, Reppert SM. CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci. 2007;10:543–5.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Kume K, Zylka MJ, Sriram S, Shearman LP, Weaver DR, Jin X, et al. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999;98:193–205.PubMedCrossRefGoogle Scholar
  50. 50.
    Griffin Jr EA, Staknis D, Weitz CJ. Light-independent role of CRY1 and CRY2 in the mammalian circadian clock. Science. 1999;286:768–71.PubMedCrossRefGoogle Scholar
  51. 51.
    Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, et al. The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell. 2002;110:251–60.PubMedCrossRefGoogle Scholar
  52. 52.
    Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, et al. A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron. 2004;43:527–37.PubMedCrossRefGoogle Scholar
  53. 53.
    Albrecht U. The circadian clock. New York: Springer; 2010.CrossRefGoogle Scholar
  54. 54.
    Grimaldi B, Nakahata Y, Kaluzova M, Masubuchi S, Sassone-Corsi P. Chromatin remodeling, metabolism and circadian clocks: the interplay of CLOCK and SIRT1. Int J Biochem Cell Biol. 2009;41:81–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Hughes M, Deharo L, Pulivarthy SR, Gu J, Hayes K, Panda S, et al. High-resolution time course analysis of gene expression from pituitary. Cold Spring Harb Symp Quant Biol. 2007;72:381–6.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Duffield GE, Best JD, Meurers BH, Bittner A, Loros JJ, Dunlap JC. Circadian programs of transcriptional activation, signaling, and protein turnover revealed by microarray analysis of mammalian cells. Curr Biol CB. 2002;12:551–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Kita Y, Shiozawa M, Jin W, Majewski RR, Besharse JC, Greene AS, et al. Implications of circadian gene expression in kidney, liver and the effects of fasting on pharmacogenomic studies. Pharmacogenetics. 2002;12:55–65.PubMedCrossRefGoogle Scholar
  58. 58.
    Storch K-F, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, et al. Extensive and divergent circadian gene expression in liver and heart. Nature. 2002;417:78–83.PubMedCrossRefGoogle Scholar
  59. 59.
    Rudic RD, McNamara P, Reilly D, Grosser T, Curtis A-M, Price TS, et al. Bioinformatic analysis of circadian gene oscillation in mouse aorta. Circulation. 2005;112:2716–24.PubMedCrossRefGoogle Scholar
  60. 60.
    Young ME, Razeghi P, Cedars AM, Guthrie PH, Taegtmeyer H. Intrinsic diurnal variations in cardiac metabolism and contractile function. Circ Res. 2001;89:1199–208.PubMedCrossRefGoogle Scholar
  61. 61.
    Nakabayashi H, Ohta Y, Yamamoto M, Susuki Y, Taguchi A, Tanabe K, et al. Clock-controlled output gene Dbp is a regulator of Arnt/Hif-1β gene expression in pancreatic islet β-cells. Biochem Biophys Res Commun. 2013;434:370–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Koike N, Hida A, Numano R, Hirose M, Sakaki Y, Tei H. Identification of the mammalian homologues of the Drosophila timeless gene, Timeless1. FEBS Lett. 1998;441:427–31.PubMedCrossRefGoogle Scholar
  63. 63.
    Hoffman AE, Zheng T, Stevens RG, Ba Y, Zhang Y, Leaderer D, et al. Clock-cancer connection in non-Hodgkin’s lymphoma: a genetic association study and pathway analysis of the circadian gene cryptochrome 2. Cancer Res. 2009;69:3605–13.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Edery I. A master CLOCK hard at work brings rhythm to the transcriptome. Genes Dev. 2011;25:2321–6.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.PubMedCrossRefGoogle Scholar
  66. 66.
    Lee JH, Sancar A. Regulation of apoptosis by the circadian clock through NF-kappaB signaling. Proc Natl Acad Sci U S A. 2011;108:12036–41.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Iurisci I, Valet F, Giacchetti S, Delaloge S, Brain E, Pierga J, et al. Relations of circadian clocks genes with endocrine, proliferation, differentiation, and P53 mutation status in human locally invasive primary breast cancer. J Clin Oncol. 2010;28:15s.Google Scholar
  68. 68.
    Koyanagi S, Kuramoto Y, Nakagawa H, Aramaki H, Ohdo S, Soeda S, et al. A molecular mechanism regulating circadian expression of vascular endothelial growth factor in tumor cells. Cancer Res. 2003;63:7277–83.PubMedGoogle Scholar
  69. 69.
    Ohdo S, Koyanagi S, Matsunaga N. Chronopharmacological strategies: intra- and inter-individual variability of molecular clock. Adv Drug Deliv Rev. 2010;62:885–97.PubMedCrossRefGoogle Scholar
  70. 70.
    Jensen LD, Cao Y. Clock controls angiogenesis. Cell Cycle. 2013;12:405–8.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Borgs L, Beukelaers P, Vandenbosch R, Belachew S, Nguyen L, Malgrange B. Cell ‘circadian’ cycle: new role for mammalian core clock genes. Cell Cycle. 2009;8:832–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Kino T, Chrousos GP. Acetylation-mediated epigenetic regulation of glucocorticoid receptor activity: circadian rhythm-associated alterations of glucocorticoid actions in target tissues. Mol Cell Endocrinol. 2011;336:23–30.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Nader N, Chrousos GP, Kino T. Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications. FASEB J. 2009;23:1572–83.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Valles SL, Benlloch M, Rodriguez ML, Mena S, Pellicer JA, Asensi M, et al. Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism. J Transl Med. 2013;11:72.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Zanello SB, Jackson DM, Holick MF. Expression of the circadian clock genes clock and period1 in human skin. J Invest Dermatol. 2000;115:757–60.PubMedCrossRefGoogle Scholar
  76. 76.
    Bjarnason GA, Jordan RC, Wood PA, Li Q, Lincoln DW, Sothern RB, et al. Circadian expression of clock genes in human oral mucosa and skin: association with specific cell-cycle phases. Am J Pathol. 2001;158:1793–801.PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Zieker D, Jenne I, Koenigsrainer I, Zdichavsky M, Nieselt K, Buck K, et al. Circadian expression of clock- and tumor suppressor genes in human oral mucosa. Cell Physiol Biochem. 2010;26:155–66.PubMedCrossRefGoogle Scholar
  78. 78.
    Sandu C, Dumas M, Malan A, Sambakhe D, Marteau C, Nizard C, et al. Human skin keratinocytes, melanocytes, and fibroblasts contain distinct circadian clock machineries. Cell Mol Life Sci. 2012;69:3329–39.PubMedCrossRefGoogle Scholar
  79. 79.
    Tanioka M, Yamada H, Doi M, Bando H, Yamaguchi Y, Nishigori C, et al. Molecular clocks in mouse skin. J Invest Dermatol. 2009;129:1225–31.PubMedCrossRefGoogle Scholar
  80. 80.
    Materljan E, Zamolo G, Petković M, Ivosević D, Popović B, Materljan M, et al. Malignant skin melanoma in Croatia. Coll Antropol. 2009;33:1363–8.PubMedGoogle Scholar
  81. 81.
    Slominski A, Wortsman J, Carlson AJ, Matsuoka LY, Balch CM, Mihm MC. Malignant melanoma. Arch Pathol Lab Med. 2001;125:1295–306.PubMedGoogle Scholar
  82. 82.
    Rigel DS. Epidemiology of melanoma. Semin Cutan Med Surg. 2010;29:204–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Gamaleia NF, Skivka LM, Fedorchuk AG, Shishko ED. Circadian rhythms of cytotoxic activity in peripheral blood mononuclear cells of patients with malignant melanoma. Exp Oncol. 2006;28:54–60.PubMedGoogle Scholar
  84. 84.
    Sehgal A. Molecular biology of circadian rhythms. Hoboken: Wiley; 2004.CrossRefGoogle Scholar
  85. 85.
    Slominski A, Pisarchik A, Semak I, Sweatman T, Wortsman J, Szczesniewski A, et al. Serotoninergic and melatoninergic systems are fully expressed in human skin. FASEB J. 2002;16:896–8.PubMedGoogle Scholar
  86. 86.
    Slominski A, Wortsman J, Tobin DJ. The cutaneous serotoninergic/melatoninergic system: securing a place under the sun. FASEB J. 2005;19:176–94.PubMedCrossRefGoogle Scholar
  87. 87.
    Fischer TW, Slominski A, Zmijewski MA, Reiter RJ, Paus R. Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair. Exp Dermatol. 2008;17:713–30.PubMedCrossRefGoogle Scholar
  88. 88.
    Kleszczyński K, Hardkop LH, Fischer TW. Differential effects of melatonin as a broad range UV-damage preventive dermato-endocrine regulator. Dermatoendocrinol. 2011;3:27–31.PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Tan D, Reiter RJ, Manchester LC, Yan M, El-Sawi M, Sainz RM, et al. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem. 2002;2:181–97.PubMedCrossRefGoogle Scholar
  90. 90.
    Desotelle JA, Wilking MJ, Ahmad N. The circadian control of skin and cutaneous photodamage. Photochem Photobiol. 2012;88:1037–47.PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Fischer TW, Zmijewski MA, Zbytek B, Sweatman TW, Slominski RM, Wortsman J, et al. Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines. Int J Oncol. 2006;29:665–72.PubMedGoogle Scholar
  92. 92.
    Kvaskoff M, Weinstein P. Are some melanomas caused by artificial light? Med Hypotheses. 2010;75:305–11.PubMedCrossRefGoogle Scholar
  93. 93.
    Chen W, Baler R. The rat arylalkylamine N-acetyltransferase E-box: differential use in a master vs. a slave oscillator. Brain Res Mol Brain Res. 2000;81:43–50.PubMedCrossRefGoogle Scholar
  94. 94.
    Humphries A, Wells T, Baler R, Klein DC, Carter DA. Rodent Aanat: intronic E-box sequences control tissue specificity but not rhythmic expression in the pineal gland. Mol Cell Endocrinol. 2007;270:43–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Christ E, Pfeffer M, Korf HW, von Gall C. Pineal melatonin synthesis is altered in Period1 deficient mice. Neuroscience. 2010;171:398–406.PubMedCrossRefGoogle Scholar
  96. 96.
    Chong NW, Bernard M, Klein DC. Characterization of the chicken serotonin N-acetyltransferase gene. Activation via clock gene heterodimer/E box interaction. J Biol Chem. 2000;275:32991–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med. 1999;340:1341–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Kawara S, Mydlarski R, Mamelak AJ, Freed I, Wang B, Watanabe H, et al. Low-dose ultraviolet B rays alter the mRNA expression of the circadian clock genes in cultured human keratinocytes. J Invest Dermatol. 2002;119:1220–3.PubMedCrossRefGoogle Scholar
  99. 99.
    Kang T-H, Reardon JT, Kemp M, Sancar A. Circadian oscillation of nucleotide excision repair in mammalian brain. Proc Natl Acad Sci U S A. 2009;106:2864–7.PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Kang T-H, Lindsey-Boltz LA, Reardon JT, Sancar A. Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. Proc Natl Acad Sci U S A. 2010;107:4890–5.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Gaddameedhi S, Selby CP, Kaufmann WK, Smart RC, Sancar A. Control of skin cancer by the circadian rhythm. Proc Natl Acad Sci U S A. 2011;108:18790–5.PubMedCentralPubMedCrossRefGoogle Scholar
  102. 102.
    Wang Y, Digiovanna JJ, Stern JB, Hornyak TJ, Raffeld M, Khan SG, et al. Evidence of ultraviolet type mutations in xeroderma pigmentosum melanomas. Proc Natl Acad Sci U S A. 2009;106:6279–84.PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Geyfman M, Kumar V, Liu Q, Ruiz R, Gordon W, Espitia F, et al. Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis. Proc Natl Acad Sci U S A. 2012;109:11758–63.PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Kraljevic S, Sedic M, Scott M, Gehrig P, Schlapbach R, Pavelic K. Casting light on molecular events underlying anti-cancer drug treatment: what can be seen from the proteomics point of view? Cancer Treat Rev. 2006;32:619–29.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Elitza P. Markova-Car
    • 1
    Email author
  • Davor Jurišić
    • 2
  • Nataša Ilić
    • 1
  • Sandra Kraljević Pavelić
    • 1
  1. 1.Department of BiotechnologyUniversity of RijekaRijekaCroatia
  2. 2.Department for Plastic and Reconstructive Surgery, Clinic for SurgeryUniversity Hospital Centre RijekaRijekaCroatia

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