Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives

Stephen G. Grant; Melissa A. Melan; Jean J. Latimer; Paula A. Witt-Enderby

doi:10.1017/S1462399409000982

Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives

Published online by Cambridge University Press: 05 February 2009

Stephen G. Grant ,

Melissa A. Melan ,

Jean J. Latimer and

Paula A. Witt-Enderby

Show author details

Stephen G. Grant: Affiliation:
University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA. Center for Environmental Oncology, University of Pittsburgh, Pittsburgh, PA 15232, USA.
Melissa A. Melan: Affiliation:
Division of Molecular Diagnostics, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Jean J. Latimer: Affiliation:
University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA. Center for Environmental Oncology, University of Pittsburgh, Pittsburgh, PA 15232, USA.
Paula A. Witt-Enderby*: Affiliation:
University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA. Center for Environmental Oncology, University of Pittsburgh, Pittsburgh, PA 15232, USA. Division of Pharmaceutical Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA 15282, USA.
*: *Corresponding author: Paula A. Witt-Enderby, Division of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, 421 Mellon Hall, Pittsburgh, PA 15282, USA. Tel: +1 412 396 4346; Fax: +1 412 396 5599; E-mail: [email protected]

Article contents

Abstract
References

Get access

Rights & Permissions

Abstract

Recent studies have suggested that the pineal hormone melatonin may protect against breast cancer, and the mechanisms underlying its actions are becoming clearer. Melatonin works through receptors and distinct second messenger pathways to reduce cellular proliferation and to induce cellular differentiation. In addition, independently of receptors melatonin can modulate oestrogen-dependent pathways and reduce free-radical formation, thus preventing mutation and cellular toxicity. The fact that melatonin works through a myriad of signalling cascades that are protective to cells makes this hormone a good candidate for use in the clinic for the prevention and/or treatment of cancer. This review summarises cellular mechanisms governing the action of melatonin and then considers the potential use of melatonin in breast cancer prevention and treatment, with an emphasis on improving clinical outcomes.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e5

DOI: https://doi.org/10.1017/S1462399409000982 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Reiter, R.J. (1991) Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocrine Reviews 12, 151-180CrossRef Google Scholar PubMed

2Pandi-Perumal, S.R. et al. (2007) Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs 21, 995-1018CrossRef Google Scholar PubMed

3Witt-Enderby, P.A. et al. (2003) Melatonin receptors and their regulation: biochemical and structural mechanisms. Life Sciences 72, 2183-2198CrossRef Google Scholar PubMed

4Poirel, V.J. et al. (2002) MT1 melatonin receptor mRNA expression exhibits a circadian variation in the rat suprachiasmatic nuclei. Brain Research 946, 64-71CrossRef Google Scholar PubMed

5Gauer, F. et al. (1993) Daily rhythms of melatonin binding sites in the rat pars tuberalis and suprachiasmatic nuclei; evidence for a regulation of melatonin receptors by melatonin itself. Neuroendocrinology 57, 120-126CrossRef Google Scholar

6Gauer, F. et al. (1994) Daily variations in melatonin receptor density of rat pars tuberalis and suprachiasmatic nuclei are distinctly regulated. Brain Research 641, 92-98CrossRef Google Scholar PubMed

7Ostrowska, Z. et al. (2003) Influence of lighting conditions on daily rhythm of bone metabolism in rats and possible involvement of melatonin and other hormones in this process. Endocrine Regulations 37, 163-174Google Scholar PubMed

8Bailey, M.J. et al. (2003) Transcriptional profiling of the chick pineal gland, a photoreceptive circadian oscillator and pacemaker. Molecular Endocrinology 17, 2084-2095CrossRef Google Scholar PubMed

9Bailey, M.J. et al. (2004) Transcriptional profiling of circadian patterns of mRNA expression in the chick retina. Journal of Biological Chemistry 279, 52247-52254CrossRef Google Scholar PubMed

10Blask, D.E., Sauer, L.A. and Dauchy, R.T. (2002) Melatonin as a chronobiotic/anticancer agent: cellular, biochemical, and molecular mechanisms of action and their implications for circadian-based cancer therapy. Current Topics in Medicinal Chemistry 2, 113-132CrossRef Google Scholar PubMed

11Rutter, J., Reick, M. and McKnight, S.L. (2002) Metabolism and the control of circadian rhythms. Annual Review of Biochemistry 71, 307-331CrossRef Google Scholar PubMed

12Ravindra, T., Lakshmi, N.K. and Ahuja, Y.R. (2006) Melatonin in pathogenesis and therapy of cancer. Indian Journal of Medical Sciences 60, 523-535CrossRef Google Scholar PubMed

13Jasser, S.A., Blask, D.E. and Brainard, G.C. (2006) Light during darkness and cancer: relationships in circadian photoreception and tumor biology. Cancer Causes and Control 17, 515-523CrossRef Google Scholar PubMed

14Reiter, R.J. et al. (2007) Light at night, chronodisruption, melatonin suppression, and cancer risk: a review. Critical Reviews in Oncogenesis 13, 303-328CrossRef Google Scholar PubMed

15Shadan, F.F. (2007) Circadian tempo: a paradigm for genome stability? Medical Hypotheses 68, 883-891CrossRef Google Scholar PubMed

16Valtonen, M. et al. (2005) Effect of melatonin-rich night-time milk on sleep and activity in elderly institutionalized subjects. Nordic Journal of Psychiatry 59, 217-221CrossRef Google Scholar PubMed

17Gubin, D.G. et al. (2006) The circadian body temperature rhythm in the elderly: effect of single daily melatonin dosing. Chronobiology International 23, 639-658CrossRef Google Scholar PubMed

18Marks, F., Furstenberger, G. and Muller-Decker, K. (2007) Tumor promotion as a target of cancer prevention. Recent Results in Cancer Research 174, 37-47CrossRef Google Scholar PubMed

19Panzer, A. and Viljoen, M. (1997) The validity of melatonin as an oncostatic agent. Journal of Pineal Research 22, 184-202CrossRef Google Scholar PubMed

20Vijayalaxmi, et al. (2002) Melatonin: from basic research to cancer treatment clinics. Journal of Clinical Oncology 20, 2575-2601CrossRef Google Scholar PubMed

21Cos, S. and Sanchez-Barcelo, E.J. (2000) Melatonin, experimental basis for a possible application in breast cancer prevention and treatment. Histology and Histopathology 15, 637-647Google Scholar PubMed

22Cos, S. and Sanchez-Barcelo, E.J. (2000) Melatonin and mammary pathological growth. Frontiers in Neuroendocrinology 21, 133-170CrossRef Google Scholar PubMed

23Lenoir, V. et al. (2005) Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague-Dawley rat. Breast Cancer Research 7, R470-476CrossRef Google Scholar

24Blask, D.E. et al. (2005) Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats. Cancer Research 65, 11174-11184CrossRef Google Scholar PubMed

25Cos, S. and Blask, D.E. (1994) Melatonin modulates growth factor activity in MCF-7 human breast cancer cells. Journal of Pineal Research 17, 25-32CrossRef Google Scholar PubMed

26Baturin, D.A. et al. (2001) The effect of light regimen and melatonin on the development of spontaneous mammary tumors in HER-2/neu transgenic mice is related to a downregulation of HER-2/neu gene expression. Neuroendocrinology Letters 22, 441-447Google Scholar PubMed

27Rato, A.G. et al. (1999) Melatonin blocks the activation of estrogen receptor for DNA binding. FASEB Journal 13, 857-868CrossRef Google Scholar PubMed

28Kiefer, T. et al. (2002) Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells. Breast Cancer Research and Treatment 71, 37-45CrossRef Google Scholar PubMed

29Sanchez-Barcelo, E.J. et al. (2005) Melatonin-estrogen interactions in breast cancer. Journal of Pineal Research 38, 217-222CrossRef Google Scholar PubMed

30del Rio, B. et al. (2004) Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin. Journal of Biological Chemistry 279, 38294-38302CrossRef Google Scholar PubMed

31Satomura, K. et al. (2007) Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo. Journal of Pineal Research 42, 231-239CrossRef Google Scholar PubMed

32Sanchez-Hidalgo, M. et al. (2007) Melatonin inhibits fatty acid-induced triglyceride accumulation in ROS17/2.8 cells: implications for osteoblast differentiation and osteoporosis. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 292, R2208-2215CrossRef Google Scholar PubMed

33Schuster, C. et al. (2005) The human MT1 melatonin receptor stimulates cAMP production in the human neuroblastoma cell line SH-SY5Y cells via a calcium-calmodulin signal transduction pathway. Journal of Neuroendocrinology 17, 170-178CrossRef Google Scholar

34Johnston, J.D. et al. (2006) Regulation of MT melatonin receptor expression in the foetal rat pituitary. Journal of Neuroendocrinology 18, 50-56CrossRef Google Scholar PubMed

35Radio, N.M., Doctor, J.S. and Witt-Enderby, P.A. (2006) Melatonin enhances alkaline phosphatase activity in differentiating human adult mesenchymal stem cells grown in osteogenic medium via MT2 melatonin receptors and the MEK/ERK (1/2) signaling cascade. Journal of Pineal Research 40, 332-342CrossRef Google Scholar PubMed

36Sainz, R.M. et al. (2005) Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism. Prostate 63, 29-43CrossRef Google Scholar

37Bellon, A. et al. (2007) Melatonin induces neuritogenesis at early stages in N1E-115 cells through actin rearrangements via activation of protein kinase C and Rho-associated kinase. Journal of Pineal Research 42, 214-221CrossRef Google Scholar PubMed

38Moriya, T. et al. (2007) Melatonin influences the proliferative and differentiative activity of neural stem cells. Journal of Pineal Research 42, 411-418CrossRef Google Scholar PubMed

39Jimenez-Jorge, S. et al. (2005) Melatonin synthesis and melatonin-membrane receptor (MT1) expression during rat thymus development: role of the pineal gland. Journal of Pineal Research 39, 77-83CrossRef Google Scholar PubMed

40Witt-Enderby, P.A. et al. (2006) Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy. Journal of Pineal Research 41, 297-305CrossRef Google Scholar PubMed

41Bondi, C.D. et al. (2008) MT1 melatonin receptor internalization underlies melatonin-induced morphologic changes in Chinese hamster ovary cells and these processes are dependent on Gi proteins, MEK 1/2 and microtubule modulation. Journal of Pineal Research 44, 288-298CrossRef Google Scholar PubMed

42Jarzynka, M.J. et al. (2006) Modulation of melatonin receptors and G-protein function by microtubules. Journal of Pineal Research 41, 324-336CrossRef Google Scholar PubMed

43Witt-Enderby, P.A. and Dubocovich, M.L. (1996) Characterization and regulation of the human ML1A melatonin receptor stably expressed in Chinese hamster ovary cells. Molecular Pharmacology 50, 166-174Google Scholar PubMed

44Brydon, L. et al. (1999) Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins. Molecular Endocrinology 13, 2025-2038CrossRef Google Scholar

45Cini, G. et al. (2005) Antiproliferative activity of melatonin by transcriptional inhibition of cyclin D1 expression: a molecular basis for melatonin-induced oncostatic effects. Journal of Pineal Research 39, 12-20CrossRef Google Scholar PubMed

46Dai, J. et al. (2002) Modulation of intracellular calcium and calmodulin by melatonin in MCF-7 human breast cancer cells. Journal of Pineal Research 32, 112-119CrossRef Google Scholar PubMed

47Martinez-Campa, C. et al. (2006) Melatonin inhibits both ER alpha activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium. Journal of Pineal Research 40, 291-296CrossRef Google Scholar PubMed

48Roy, D. et al. (2001) Cyclical regulation of GnRH gene expression in GT1–7 GnRH-secreting neurons by melatonin. Endocrinology 142, 4711-4720CrossRef Google Scholar PubMed

49Cos, S. et al. (2005) Melatonin modulates aromatase activity in MCF-7 human breast cancer cells. Journal of Pineal Research 38, 136-142CrossRef Google Scholar PubMed

50Cos, S. et al. (2006) Melatonin inhibits the growth of DMBA-induced mammary tumors by decreasing the local biosynthesis of estrogens through the modulation of aromatase activity. International Journal of Cancer 118, 274-278CrossRef Google Scholar PubMed

51Reiter, R.J. et al. (2007) Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. Acta Biochimica Polonica 54, 1-9CrossRef Google Scholar PubMed

52Tan, D.X. et al. (2007) Melatonin as a naturally occurring co-substrate of quinone reductase-2, the putative MT3 melatonin membrane receptor: hypothesis and significance. Journal of Pineal Research 43, 317-320CrossRef Google Scholar PubMed

53Nosjean, O. et al. (2000) Identification of the melatonin-binding site MT3 as the quinone reductase 2. Journal of Biological Chemistry 275, 31311-31317CrossRef Google Scholar PubMed

54Nosjean, O. et al. (2001) Comparative pharmacological studies of melatonin receptors: MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2. Biochemical Pharmacology 61, 1369-1379CrossRef Google Scholar PubMed

55Dziegiel, P., Podhorska-Okolow, M. and Zabel, M. (2008) Melatonin: adjuvant therapy of malignant tumors. Medical Science Monitor 14, RA64-70Google Scholar PubMed

56Pawlikowski, M., Winczyk, K. and Karasek, M. (2002) Oncostatic action of melatonin: facts and question marks. Neuroendocrinolology Letters 23 Suppl 1, 24-29Google Scholar PubMed

57Moss, R.W. (2004) Cancer and complementary and alternative medicine in Italy: personal observations and historical considerations. Integrative Cancer Therapies 3, 173-188CrossRef Google Scholar PubMed

58Lissoni, P. et al. (1991) Modulation of interleukin-2-induced macrophage activation in cancer patients by the pineal hormone melatonin. Journal of Biological Regulators and Homeostatic Agents 5, 154-156Google Scholar PubMed

59Carrillo-Vico, A. et al. (2003) Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its mt1 membrane receptor. FASEB Journal 17, 755-757CrossRef Google Scholar PubMed

60Leon-Blanco, M.M. et al. (2003) Melatonin inhibits telomerase activity in the MCF-7 tumor cell line both in vivo and in vitro. Journal of Pineal Research 35, 204-211CrossRef Google Scholar PubMed

61Reiter, R.J. et al. (1999) Augmentation of indices of oxidative damage in life-long melatonin-deficient rats. Mechanisms of Ageing and Development 110, 157-173CrossRef Google Scholar PubMed

62Morioka, N., Okatani, Y. and Wakatsuki, A. (1999) Melatonin protects against age-related DNA damage in the brains of female senescence-accelerated mice. Journal of Pineal Research 27, 202-209CrossRef Google Scholar PubMed

63Anisimov, V.N. et al. (2003) Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice. Experimental Gerontology 38, 449-461CrossRef Google Scholar PubMed

64Vinogradova, I.A. et al. (2007) [Effect of light regimens and melatonin on the homeostasis, life span and development of spontaneous tumors in female rats.] Advances in Gerontology 20, 40-47 [Article in Russian]Google Scholar PubMed

65Braeckman, B.P., Demetrius, L. and Vanfleteren, J.R. (2006) The dietary restriction effect in C. elegans and humans: is the worm a one-millimeter human? Biogerontology 7, 127-133CrossRef Google Scholar

66Bartsch, C. and Bartsch, H. (2006) The anti-tumor activity of pineal melatonin and cancer enhancing life styles in industrialized societies. Cancer Causes and Control 17, 559-571CrossRef Google Scholar PubMed

67Davis, S. and Mirick, D.K. (2006) Circadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in Seattle. Cancer Causes and Control 17, 539-545CrossRef Google Scholar

68Moriya, T. et al. (2007) Correlative association between circadian expression of mousePer2 gene and the proliferation of the neural stem cells. Neuroscience 146, 494-498CrossRef Google Scholar PubMed

69Gery, S. et al. (2005) Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia. Blood 106, 2827-2836CrossRef Google Scholar PubMed

70Chen, S.T. et al. (2005) Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers. Carcinogenesis 26, 1241-1246CrossRef Google Scholar PubMed

71Migliore, L. and Coppede, F. (2002) Genetic and environmental factors in cancer and neurodegenerative diseases. Mutation Research 512, 135-153CrossRef Google Scholar PubMed

72Nogues, M.R. et al. (2006) Melatonin reduces oxidative stress in erythrocytes and plasma of senescence-accelerated mice. Journal of Pineal Research 41, 142-149CrossRef Google Scholar PubMed

73Loft, S. and Poulsen, H.E. (1996) Cancer risk and oxidative DNA damage in man. Journal of Molecular Medicine 74, 297-312CrossRef Google Scholar PubMed

74Schernhammer, E.S. et al. (2004) Epidemiology of urinary melatonin in women and its relation to other hormones and night work. Cancer Epidemiology Biomarkers and Prevention 13, 936-943CrossRef Google Scholar PubMed

75Megdal, S.P. et al. (2005) Night work and breast cancer risk: a systematic review and meta-analysis. European Journal of Cancer 41, 2023-2032CrossRef Google Scholar

76Schernhammer, E.S. and Hankinson, S.E. (2005) Urinary melatonin levels and breast cancer risk. Journal of the National Cancer Institute 97, 1084-1087CrossRef Google Scholar PubMed

77Travis, R.C. et al. (2004) Melatonin and breast cancer: a prospective study. Journal of the National Cancer Institute 96, 475-482CrossRef Google Scholar PubMed

78Blask, D.E. (1993) Melatonin in oncology. In Melatonin: Biosynthesis, Physiological Effects and Clinical Applications ( Yu, H.-S. and Reiter, R.J., eds), pp. 447–476, CRC Press, Boca Raton, USAGoogle Scholar

79Tarquini, B. et al. (1994) Daytime circulating melatonin levels in smokers. Tumori 80, 229-232CrossRef Google Scholar PubMed

80Bartsch, C. et al. (1994) Diminished pineal function coincides with disturbed circadian endocrine rhythmicity in untreated primary cancer patients. Consequence of premature aging or of tumor growth? Annals of the New York Academy of Sciences 719, 502-525CrossRef Google Scholar PubMed

81Bartsch, C. et al. (1997) Nocturnal urinary 6-sulfatoxymelatonin and proliferating cell nuclear antigen-immunopositive tumor cells show strong positive correlations in patients with gastrointestinal and lung cancer. Journal of Pineal Research 23, 90-96CrossRef Google Scholar PubMed

82Blask, D.E. (1997) The melatonin rhythm in cancer patients. In Melatonin in Psychiatric and Neoplastic Disorders (Shafii, M. and Shafii, S.L., eds), pp. 243–260, American Psychiatric Press, Washington, D.C., USAGoogle Scholar

83Kusmartsev, S. and Gabrilovich, D.I. (2006) Effect of tumor-derived cytokines and growth factors on differentiation and immune suppressive features of myeloid cells in cancer. Cancer and Metastasis Reviews 25, 323-331CrossRef Google Scholar PubMed

84Kawanishi, S. and Hiraku, Y. (2006) Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation. Antioxidants and Redox Signalling 8, 1047-1058CrossRef Google Scholar PubMed

85Chen, R. et al. (2007) Inflammation, cancer and chemoresistance: taking advantage of the toll-like receptor signaling pathway. American Journal of Reproductive Immunology 57, 93-107CrossRef Google Scholar PubMed

86Burch, J.B. et al. (2007) Melatonin and estrogen in breast cyst fluids. Breast Cancer Research and Treatment 103, 331-341CrossRef Google Scholar PubMed

87Maestroni, G.J. and Conti, A. (1996) Melatonin in human breast cancer tissue: association with nuclear grade and estrogen receptor status. Laboratory Investigation 75, 557-561Google Scholar PubMed

88Poeggeler, B. (2005) Melatonin, aging, and age-related diseases: perspectives for prevention, intervention, and therapy. Endocrine 27, 201-212CrossRef Google Scholar PubMed

89Poeggeler, B. et al. (1993) Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis. Journal of Pineal Research 14, 151-168CrossRef Google Scholar PubMed

90Brozmanova, J., Dudas, A. and Henriques, J.A. (2001) Repair of oxidative DNA damage–an important factor reducing cancer risk. Minireview. Neoplasma 48, 85-93Google Scholar PubMed

91Becr VII Phase 2, (2006) Health Risks from Exposure to Low Levels of Ionizing Radiation, National Academies Press, Washington, D.C., USAGoogle Scholar

92Vesnushkin, G.M. et al. (2006) Dose-dependent inhibitory effect of melatonin on carcinogenesis induced by benzo[a]pyrene in mice. Journal of Experimental and Clinical Cancer Research 25, 507-513Google Scholar

93Lissoni, P. et al. (1996) Prevention of cytokine-induced hypotension in cancer patients by the pineal hormone melatonin. Supportive Care in Cancer 4, 313-316CrossRef Google Scholar PubMed

94Norsa, A. and Martino, V. (2007) Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status. Cancer Biotherapy and Radiopharmaceuticals 22, 50-55CrossRef Google Scholar PubMed

95Lissoni, P. et al. (1995) A biological study on the efficacy of low-dose subcutaneous interleukin-2 plus melatonin in the treatment of cancer-related thrombocytopenia. Oncology 52, 360-362CrossRef Google Scholar

96Lissoni, P. et al. (1996) The pineal hormone melatonin in hematology and its potential efficacy in the treatment of thrombocytopenia. Recenti Progressi in Medicina 87, 582-585Google Scholar

97Lissoni, P. et al. (1996) Is there a role for melatonin in the treatment of neoplastic cachexia? European Journal of Cancer 32A, 1340-1343CrossRef Google Scholar

98Cos, S. et al. (2006) Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions. Cancer Detection and Prevention 30, 118-128CrossRef Google Scholar PubMed

99Treilleux, et al. (1997) Human estrogen receptor (ER) gene promoter-P1: estradiol-independent activity and estradiol inducibility in ER+ and ER-cells. Molecular Endocrinology 11, 1319-1331Google Scholar PubMed

100Cunat, S., Hoffmann, P. and Pujol, P. (2004) Estrogens and epithelial ovarian cancer. Gynecologic Oncology 94, 25-32CrossRef Google Scholar PubMed

101Naderi, A. et al. (2007) BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines. Cancer Research 67, 6725-6736CrossRef Google Scholar

102Tiligada, E. (2006) Chemotherapy: induction of stress responses. Endocrine-Related Cancer 13 Suppl 1, S115-124CrossRef Google Scholar PubMed

103Mills, E. et al. (2005) Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. Journal of Pineal Research 39, 360-366CrossRef Google Scholar

104Vijayalaxmi, et al. (2004) Melatonin as a radioprotective agent: a review. International Journal of Radiation Oncology, Biology, Physics 59, 639-653CrossRef Google Scholar PubMed

105Lissoni, P. (2007) Biochemotherapy with standard chemotherapies plus the pineal hormone melatonin in the treatment of advanced solid neoplasms. Pathologie-Biologie 55, 201-204CrossRef Google Scholar PubMed

106Jonsson, G., Staaf, J., Olssen, E., Heidenblad, M., Vallon-Christersson, J., Osoegawa, K., de Jong, P., Oredsson, S., Ringr, M., Hoglund, M., and Borg, A. (2007) High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization. Genes Chromosomes Cancer 46, 543-558CrossRef Google Scholar PubMed

107Crespo, D. et al. (1994) Interaction between melatonin and estradiol on morphological and morphometric features of MCF-7 human breast cancer cells. Journal of Pineal Research 16, 215-222CrossRef Google Scholar PubMed

108Hill, S.M. and Blask, D.E. (1988) Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture. Cancer Research 48, 6121-6126Google Scholar PubMed

109Wenger, S.L. et al. (2004) Comparison of established cell lines at different passages by karyotype and comparative genomic hybridization. Bioscience Reports 24, 631-639CrossRef Google Scholar PubMed

110Klein, A. et al. (2006) Different mechanisms of mitotic instability in cancer cell lines. International Journal of Oncology 29, 1389-1396Google Scholar PubMed

111Chatterjee, S.K. and Zetter, B.R. (2005) Cancer biomarkers: knowing the present and predicting the future. Future Oncology 1, 37-50CrossRef Google Scholar PubMed

112Wang, Y. et al. (2007) Gene expression profiles and prognostic markers for primary breast cancer. Methods in Molecular Biology 377, 131-138CrossRef Google Scholar PubMed

113Stemke-Hale, K. et al. (2006) Molecular screening for breast cancer prevention, early detection, and treatment planning: combining biomarkers from DNA, RNA, and protein. Current Oncology Reports 8, 484-491CrossRef Google Scholar PubMed

114Reiter, R.J. and Tan, D.X. (2003) What constitutes a physiological concentration of melatonin? Journal of Pineal Research 34, 79-80CrossRef Google Scholar PubMed

115Aust, S. et al. (2005) Biotransformation of melatonin in human breast cancer cell lines: role of sulfotransferase 1A1. Journal of Pineal Research 39, 276-282CrossRef Google Scholar PubMed

Article contents

Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives

Abstract

Access options

References

References

Further reading, resources and contacts

This article has been cited by the following publications. This list is generated based on data provided by Crossref.

Article contents

Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives

Abstract

Access options

References

References

Further reading, resources and contacts

Save article to Kindle

Save article to Dropbox

Save article to Google Drive

Reply to: Submit a response

Your details

You have entered the maximum number of contributors

Conflicting interests