Advances in Therapy

, Volume 26, Issue 9, pp 886–892 | Cite as

Melatonin and tryptophan circadian profiles in patients with advanced non-small cell lung cancer

Original Research

Abstract

Introduction

Accumulating studies indicate that melatonin is a natural oncostatic agent capable of mediating the influence of the psychoneuroendocrine system on cancer growth. Although there is increasing evidence to show that the pineal gland may play a role in human non-small cell lung cancer (NSCLC), there is uncertainty about circadian profiles of melatonin, its precursor tryptophan, and its major metabolite, 6-sulfatoxymelatonin (6-OH-MLT) in NSCLC patients before and after treatment with standard chemotherapy (cisplatin plus vinorelbine). The aim of this study was to investigate the concentration changes of melatonin, tryptophan, and 6-OH-MLT in NSCLC patients treated with standard chemotherapy.

Methods

We examined the circadian melatonin, tryptophan, and 6-OH-MLT rhythms in 30 patients suffering from advanced-stage NSCLC and compared them with those of 63 healthy volunteers free from neoplastic disease. Blood samples were collected at 12 noon and 12 midnight. Urine samples were collected at 7 am and 4 pm. The levels of melatonin in serum and of 6-OH-MLT in urine were measured by high-performance liquid chromatography. The concentration of amino acids including tryptophan in serum was measured by amino acid analyzer.

Results

Melatonin, tryptophan, and 6-OH-MLT concentrations were significantly lower in cancer patients, in comparison with healthy subjects. A significant inverse correlation between melatonin and tryptophan was observed. Additionally, after three cycles of standard chemotherapy, there was a tendency of melatonin, tryptophan, and 6-OH-MLT concentrations to progressively decrease in NSCLC patients.

Conclusion

The results of the present study indicate that the presence of NSCLC influences the metabolism of melatonin, and chemotherapy in NSCLC patients may progressively decrease the production of melatonin.

Keywords

6-sulfatoxymelatonin circadian rhythm melatonin non-small cell lung cancer tryptophan 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cardinali DP, Golombek DA, Rosenstein RE, Cutrera RA, Esquifino AI. Melatonin site and mechanism of action: single or multiple? J Pineal Res. 1997;23:32–39.CrossRefPubMedGoogle Scholar
  2. 2.
    Abe M, Itoh MT, Miyata M, Ishikawa S, Sumi Y. Detection of melatonin, its precursors and related enzyme activities in rabbit lens. Exp Eye Res. 1999;68:255–262.CrossRefPubMedGoogle Scholar
  3. 3.
    Jung B, Ahmad N. Melatonin in cancer management: progress and promise. Cancer Res. 2006;66:9789–9793.CrossRefPubMedGoogle Scholar
  4. 4.
    Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ. A review of the multiple actions of melatonin on the immune system. Endocrine. 2005;27:189–200.CrossRefPubMedGoogle Scholar
  5. 5.
    Bartsch C, Bartsch H. The anti-tumor activity of pineal melatonin and cancer enhancing life styles in industrialized societies. Cancer Causes Control. 2006;17:559–571.CrossRefPubMedGoogle Scholar
  6. 6.
    Carlson LE, Campbell TS, Garland SN, Grossman P. Associations among salivary cortisol, melatonin, catecholamines, sleep quality and stress in women with breast cancer and healthy controls. J Behav Med. 2007;30:45–58.CrossRefPubMedGoogle Scholar
  7. 7.
    Ravindra T, Lakshmi NK, Ahuja YR. Melatonin in pathogenesis and therapy of cancer. Indian J Med Sci. 2006;60:523–535.CrossRefPubMedGoogle Scholar
  8. 8.
    Nagata C, Nagao Y, Yamamoto S, Shibuya C, Kashiki Y, Shimizu H. Light exposure at night, urinary 6-sulfatoxymelatonin, and serum estrogens and androgens in postmenopausal Japanese women. Cancer Epidemiol Biomarkers Prev. 2008;17:1418–1423.CrossRefPubMedGoogle Scholar
  9. 9.
    Schernhammer ES, Berrino F, Krogh V, et al. Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2008;100:898–905.CrossRefPubMedGoogle Scholar
  10. 10.
    Wu AH, Wang R, Koh WP, Stanczyk FZ, Lee HP, Yu MC. Sleep duration, melatonin and breast cancer among Chinese women in Singapore. Carcinogenesis. 2008;29:1244–1248.CrossRefPubMedGoogle Scholar
  11. 11.
    Tam CW, Chan KW, Liu VW, Pang B, Yao KM, Shiu SY. Melatonin as a negative mitogenic hormonal regulator of human prostate epithelial cell growth: potential mechanisms and clinical significance. J Pineal Res. 2008;45:403–412.CrossRefPubMedGoogle Scholar
  12. 12.
    Karasek M, Kowalski AJ, Suzin J, Zylinska K, Swietoslawski J. Serum melatonin circadian profiles in women suffering from cervical cancer. J Pineal Res. 2005;39:73–76.CrossRefPubMedGoogle Scholar
  13. 13.
    Aldeghi R, Lissoni P, Barni S, et al. Low-dose interleukin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma. Eur J Cancer. 1994;30A:167–170.CrossRefPubMedGoogle Scholar
  14. 14.
    Barni S, Lissoni P, Cazzaniga M, et al. A randomized study of low-dose subcutaneous interleukin-2 plus melatonin versus supportive care alone in metastatic colorectal cancer patients progressing under 5-fluorouracil and folates. Oncology. 1995;52:243–245.CrossRefPubMedGoogle Scholar
  15. 15.
    Dziadziuszko R, Hirsch FR. Advances in genomic and proteomic studies of non-small-cell lung cancer: clinical and translational research perspective. Clin Lung Cancer. 2008;9:78–84.CrossRefPubMedGoogle Scholar
  16. 16.
    Motoyama A, Kanda T, Namba R. Direct determination of endogenous melatonin in human saliva by column-switching semi-microcolumn liquid chromatography/mass spectrometry with on-line analyte enrichment. Rapid Commun Mass Spectrom. 2004;18:1250–1258.CrossRefPubMedGoogle Scholar
  17. 17.
    Eriksson K, Ostin A, Levin JO. Quantification of melatonin in human saliva by liquid chromatographytandem mass spectrometry using stable isotope dilution. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;794:115–123.CrossRefPubMedGoogle Scholar
  18. 18.
    Muc-Wierzgon M, Nowakowska-Zajdel E, Zubelewicz B, et al. Circadian fluctuations of melatonin, tumor necrosis factor-alpha and its soluble receptors in the circulation of patients with advanced gastrointestinal cancer. J Exp Clin Cancer Res. 2003;22:171–178.PubMedGoogle Scholar
  19. 19.
    Bartsch C, Bartsch H, Fuchs U, Lippert TH, Bellmann O, Gupta D. Stage-dependent depression of melatonin in patients with primary breast cancer. Correlation with prolactin, thyroid stimulating hormone, and steroid receptors. Cancer. 1989;64:426–433.CrossRefPubMedGoogle Scholar
  20. 20.
    Bartsch C, Bartsch H, Bellmann O, Lippert TH. Depression of serum melatonin in patients with primary breast cancer is not due to an increased peripheral metabolism. Cancer. 1991;67:1681–1684.CrossRefPubMedGoogle Scholar
  21. 21.
    Barba M, Cavalleri A, Schunemann HJ, et al. Reliability of urinary 6-sulfatoxymelatonin as a biomarker in breast cancer. Int J Biol Markers. 2006;21:242–245.PubMedGoogle Scholar
  22. 22.
    Travis RC, Allen DS, Fentiman IS, Key TJ. Melatonin and breast cancer: a prospective study. J Natl Cancer Inst. 2004;96:475–482.PubMedCrossRefGoogle Scholar
  23. 23.
    Kos-Kudla B, Ostrowska Z, Kozlowski A, et al. Circadian rhythm of melatonin in patients with colorectal carcinoma. Neuro Endocrinol Lett. 2002;23:239–242.PubMedGoogle Scholar
  24. 24.
    Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev. 2009;89:381–410.CrossRefPubMedGoogle Scholar
  25. 25.
    Lai L, Yuan L, Chen Q, et al. The Galpha(i) and Galpha(q) proteins mediate the effects of melatonin on steroid/thyroid hormone receptor transcriptional activity and breast cancer cell proliferation. J Pineal Res. 2008;45:476–488.CrossRefPubMedGoogle Scholar
  26. 26.
    Dziegiel P, Podhorska-Okolow M, Zabel M. Melatonin: adjuvant therapy of malignant tumors. Med Sci Monit. 2008;14:RA64–RA70.PubMedGoogle Scholar
  27. 27.
    Otalora BB, Madrid JA, Alvarez N, Vicente V, Rol MA. Effects of exogenous melatonin and circadian synchronization on tumor progression in melanoma-bearing C57BL6 mice. J Pineal Res. 2008;44:307–315.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Healthcare Communications 2009

Authors and Affiliations

  • Shilian Hu
    • 1
  • Gan Shen
    • 1
  • Shi Yin
    • 1
  • Weiping Xu
    • 1
  • Bing Hu
    • 2
  1. 1.Department of Geriatrics, Anhui Evidence-Based Medicine Center, Anhui Geriatrics InstituteThe Affiliated Provincial Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Department of OncologyThe Affiliated Provincial Hospital of Anhui Medical UniversityHefeiChina

Personalised recommendations