PHYTOMELATONIN AND CANCER PREVENTION

Summary

Principal Investigator: David Blask
Abstract: The long-term goal of this research project is to better understand the role of melatonin derived from the pineal gland, in conjunction with phytomelatonin ingested in the diet, in the prevention of the growth of human malignancies in the context of biological timing. Melatonin inhibition of tissue-isolated tumor (rat hepatoma 7288CTC) growth in vivo occurs via inhibitory G protein-coupled melatonin receptor-mediated suppression of cAMP and a resultant blockade of tumor linoleic acid (LA) uptake and 13-hydroxyoctadecadienoic acid (13-HODE). This occurs via inhibition of fatty acid transport protein (FATP) function. 13-HODE, which amplifies the epidermal growth factor EGF-mitogenic signaling pathway, is the mitogenic signal responsible for LA-dependent tumor growth. The hypothesis to be tested is: Melatonin, derived from the pineal gland and dietary sources, plays a significant role in the prevention of human tumor development and growth; the mechanism of action is via melatonin receptor-mediated suppression of cAMP-dependent FATP function and/or expression leading to a blockade of tumor LA uptake and production of 13-HODE in the context of circadian time structure. The first aim is to assess the effects of dietary melatonin on tissue-isolated human tumor growth and LA metabolism in vivo. The second aim is to further define the melatonin signal transduction mechanisms involved in the regulation of tissue-isolated tumor LA metabolism and growth in vivo. The third aim is to examine the interactions among FATP function, melatonin inhibitory signaling, and EGF stimulatory signaling in the control of tissue-isolated tumor LA metabolism and growth. The fourth aim is to further define the circadian rhythm regulation of FA metabolism simultaneously in tissue-isolated tumors and contralateral fat pads and the role of melatonin. The proposed studies will help to provide a scientific rationale for the development of new dietary recommendations that consider LA intake, circadian-timed melatonin supplementation and/or photoperiodic alterations for the prevention and treatment of cancer growth and cachexia.
Funding Period: 1997-09-15 - 2005-04-30
more information: NIH RePORT

Top Publications

  1. pmc Circadian regulation of molecular, dietary, and metabolic signaling mechanisms of human breast cancer growth by the nocturnal melatonin signal and the consequences of its disruption by light at night
    David E Blask
    Laboratory of Chrono Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, LA, USA
    J Pineal Res 51:259-69. 2011
  2. ncbi Eicosapentaenoic acid suppresses cell proliferation in MCF-7 human breast cancer xenografts in nude rats via a pertussis toxin-sensitive signal transduction pathway
    Leonard A Sauer
    Bassett Research Institute, Cooperstown, NY 13326, USA
    J Nutr 135:2124-9. 2005
  3. ncbi Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal
    David E Blask
    Laboratory of Chrono Neuroendocrine Oncology, Bassett Research Institute, Cooperstown, NY 13326, USA
    Endocrine 27:179-88. 2005
  4. ncbi Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats
    David E Blask
    Laboratory of Chrono Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, New York 13326, USA
    Cancer Res 65:11174-84. 2005
  5. ncbi Human cancer xenograft perfusion in situ in rats: a new perfusion system that minimizes delivery time and maintains normal tissue physiology and responsiveness to growth-inhibitory agents
    Erin M Dauchy
    Laboratory of Chrononeuroendocrine Oncology, Bassett Research Institute, Cooperstown, NY, USA
    J Am Assoc Lab Anim Sci 45:38-44. 2006
  6. ncbi Dietary factors and growth and metabolism in experimental tumors
    Leonard A Sauer
    Bassett Research Institute, Cooperstown, NY 13326, USA
    J Nutr Biochem 18:637-49. 2007
  7. ncbi Dietary fish oil deactivates a growth-promoting signaling pathway in hepatoma 7288CTC in Buffalo rats
    Laura C Smith
    Bassett Research Institute, Cooperstown, NY 13326, USA
    Nutr Cancer 56:204-13. 2006
  8. ncbi Inhibition of fatty acid transport and proliferative activity in tissue-isolated human squamous cell cancer xenografts perfused in situ with melatonin or eicosapentaenoic or conjugated linoleic acids
    Robert T Dauchy
    Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, NY, USA
    Comp Med 57:377-82. 2007

Scientific Experts

  • David E Blask
  • Leonard A Sauer
  • Robert T Dauchy
  • Erin M Dauchy
  • Leslie K Davidson
  • Darin T Lynch
  • Jean A Krause
  • Laura C Smith
  • Robert P Tirrell
  • Peter Van der Riet
  • Paul C Tirrell
  • Lia M Blue

Detail Information

Publications8

  1. pmc Circadian regulation of molecular, dietary, and metabolic signaling mechanisms of human breast cancer growth by the nocturnal melatonin signal and the consequences of its disruption by light at night
    David E Blask
    Laboratory of Chrono Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, LA, USA
    J Pineal Res 51:259-69. 2011
    ....
  2. ncbi Eicosapentaenoic acid suppresses cell proliferation in MCF-7 human breast cancer xenografts in nude rats via a pertussis toxin-sensitive signal transduction pathway
    Leonard A Sauer
    Bassett Research Institute, Cooperstown, NY 13326, USA
    J Nutr 135:2124-9. 2005
    ..The results suggest that EPA regulates cell proliferation in MCF-7 xenografts via a novel inhibitory G protein-coupled, (n-3) FFA receptor-mediated signal transduction pathway...
  3. ncbi Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal
    David E Blask
    Laboratory of Chrono Neuroendocrine Oncology, Bassett Research Institute, Cooperstown, NY 13326, USA
    Endocrine 27:179-88. 2005
    ..Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life...
  4. ncbi Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats
    David E Blask
    Laboratory of Chrono Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, New York 13326, USA
    Cancer Res 65:11174-84. 2005
    ..These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers...
  5. ncbi Human cancer xenograft perfusion in situ in rats: a new perfusion system that minimizes delivery time and maintains normal tissue physiology and responsiveness to growth-inhibitory agents
    Erin M Dauchy
    Laboratory of Chrononeuroendocrine Oncology, Bassett Research Institute, Cooperstown, NY, USA
    J Am Assoc Lab Anim Sci 45:38-44. 2006
    ..This new system provides rapid perfusate delivery for use with both normal and neoplastic tissues while maintaining normal physiologic tissue parameters...
  6. ncbi Dietary factors and growth and metabolism in experimental tumors
    Leonard A Sauer
    Bassett Research Institute, Cooperstown, NY 13326, USA
    J Nutr Biochem 18:637-49. 2007
    ....
  7. ncbi Dietary fish oil deactivates a growth-promoting signaling pathway in hepatoma 7288CTC in Buffalo rats
    Laura C Smith
    Bassett Research Institute, Cooperstown, NY 13326, USA
    Nutr Cancer 56:204-13. 2006
    ..These results provide in vivo evidence that dietary fish oil suppressed a specific linoleic acid-dependent, inhibitory G protein-coupled, growth-promoting signaling pathway in rat hepatoma 7288CTC...
  8. ncbi Inhibition of fatty acid transport and proliferative activity in tissue-isolated human squamous cell cancer xenografts perfused in situ with melatonin or eicosapentaenoic or conjugated linoleic acids
    Robert T Dauchy
    Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, NY, USA
    Comp Med 57:377-82. 2007
    ....