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Part I: Molecular Biology
Invited Lectures

New Actions of Melatonin on Tumor Metabolism and Growth

Blask D.E. · Sauer L.A. · Dauchy R. · Holowachuk E.W. · Ruhoff M.S.

Author affiliations

Bassett Research Institute, Mary Imogene Bassett Hospital, Cooperstown, N.Y., USA

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Biol Signals Recept 1999;8:49–55

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Article / Publication Details

First-Page Preview
Abstract of Part I: Molecular Biology<br>Invited Lectures

Published online: March 19, 1999
Issue release date: January – April

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 1

ISSN: 1424-862X (Print)
eISSN: 1424-8638 (Online)

For additional information: https://www.karger.com/NSG

Abstract

Melatonin is an important inhibitor of cancer growth promotion while the essential polyunsaturated fatty acid, linoleic acid is an important promoter of cancer progression. Following its rapid uptake by tumor tissue, linoleic acid is oxidized via a lipoxygenase to the growth-signaling molecule, 13-hydroxyoctadecadienoic acid (13-HODE) which stimulates epidermal growth factor (EGF)-dependent mitogenesis. The uptake of plasma linoleic acid and its metabolism to 13-HODE by rat hepatoma 7288CTC, which expresses both fatty acid transport protein and melatonin receptors, is inhibited by melatonin in a circadian-dependent manner. This inhibitory effect of melatonin is reversible with either pertussis toxin, forskolin or cAMP. While melatonin inhibits tumor linoleic acid uptake, metabolism and growth, pinealectomy or constant light exposure stimulates these processes. Thus, melatonin and linoleic acid represent two important environmental signals that interact in a unique manner to regulate tumor progression and ultimately the host-cancer balance.


References

  1. Blask DE: Melatonin in oncology; in Yu HS, Reiter RJ (eds): Melatonin – Biosynthesis, Physiological Effects, and Clinical Implications. Boca Raton, CRC Press, 1993, pp 447–475.
  2. Klurfield DM: Fat effects on experimental tumorigenesis. J Nutr Biochem 1995;6:201–205.
  3. Blask DE, Sauer LA, Dauchy RT: Melatonin suppression of tumor growth in vivo: A novel mechanism involving inhibition of fatty acid uptake and metabolism; in Maestroni GJM, Conti A, Reiter RJ (eds): Therapeutic Potential of Melatonin, Frontiers of Hormone Research. Basel, Karger, 1997, vol 23, pp 107–114.
  4. Blask DE, Sauer LA, Dauchy RT: Melatonin regulation of tumor growth and the role of fatty acid uptake and metabolism. Neuroendocrinol Lett 1997;18:59–62.
  5. Blask DE, Sauer LA, Dauchy RT, Holowachuk EW, Ruhoff MS: Circadian rhythm in experimental tumor carcinogenesis and progression and the role of melatonin; in Touitou Y (ed): Biological Clocks – Mechanisms and Applications. Amsterdam, Elsevier, 1998, pp 469–474.
  6. Dauchy RT, Sauer LA: Preparation of ‘tumor-isolated’ rat tumors for perfusion: A new surgical technique that preserves continuous blood flow. Lab Animal Sci 1986;36:678–681.
    External Resources
  7. Sauer LA, Dauchy RT: Identification of linoleic and arachidonic acids as the factors in hyperlipemic blood that increase [3H]thymidine incorporation in hepatoma 7288CTC perfused in situ. Cancer Res 1988;48:3106–3111.
    External Resources
  8. Sauer LA, Dauchy RT: Uptake of plasma lipids by tissue-isolated hepatoma 7288CTC and 7777 in vivo. Br J Cancer 1992;66:290–296.
  9. Sauer LA, Dauchy RT: The effect of omega-6 and omega-3 fatty acids on [3H]thymidine incorporation in hepatoma 7288CTC perfused in situ. Cancer Res 1992;66:297–303.
  10. Sauer LA, Dauchy RT, Blask DE: Dietary linoleic acid intake controls the arterial blood plasma concentration and the rates of growth and linoleic acid uptake and metabolism in hepatoma 7288CTC in Buffalo rats. J Nutrition 1997;127:1412–1421.
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    External Resources
  12. Glasgow WE, Hui R, Everhart AL, Jayawickreme SP, Angerman-Stewart J, Han BB, Eling TF: The linoleic acid metabolite (13 S)-hydroxyoctadecadienoic acid, augments the epidermal growth factor receptor signaling pathway by attenuation of receptor dephosphorylation. J Biol Chem 1997;272:19269–19276.
  13. Sauer LA, Dauchy RT, Blask DE, Armstrong BJ, Scalici S: 13-Hydroxyoctadecadienoic acid (13-HODE) is the mitogenic signal for linoleic acid-dependent growth in rat hepatoma 7288CTC in vivo (abstract). Am Assoc Cancer Res, in press.
  14. Dauchy RT, Sauer LA, Blask DE, Vaughan GM: Light contamination during the dark phase in ‘photoperiodically controlled’ animal rooms: Effect on tumor growth and metabolism in rats. Lab Animal Sci 1997;47:511–518.
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    External Resources
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    External Resources
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    External Resources
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    External Resources
  19. Cho-Chung, YS: Role of cyclic AMP receptor proteins in growth, differentiation, and suppression of malignancy: New approaches to therapy. Cancer Res 1990;50:7093–7100.
  20. Cos S, Blask DE: Melatonin modulates growth factor activity in MCF-7 human breast cancer cells. J Pineal Res 1994;17:25–32.

Article / Publication Details

First-Page Preview
Abstract of Part I: Molecular Biology<br>Invited Lectures

Published online: March 19, 1999
Issue release date: January – April

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 1

ISSN: 1424-862X (Print)
eISSN: 1424-8638 (Online)

For additional information: https://www.karger.com/NSG


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