Abstract

This research will test the hypothesis that melatonin derived from the pineal gland, modulated by light cycling or derived from foods (phytomelatonin), inhibits hepatoma growth in male and female Buffalo rats. The mechanism to be tested is that melatonin reduces the uptake of the tumor growth-promoting fatty acid, linoleic acid (LA), its metabolism to 13-HODE (13-hydroxy-9,11-octadecadienoic acid), the expression of the fatty acid transport protein, FATP, and the level of cellular glutathione (GSH). Rats will be fed purified diets supplemented with food-derived or synthetic melatonin or will be subjected to light cycling. Blood melatonin levels will be determined. Tumor growth and blood A-V fatty acid differences and tumor fatty acid uptake will be assessed. Biochemical and molecular analysis of the fatty acid transporter, FATP, and of enzymes involved in 13-HODE and GSH production will be determined. This novel hypothesis may provide important information regarding the impact of melatonin on cancer chemoprevention via inhibition of fatty acid uptake and metabolism.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA076197-03
Application #
2896251
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Milner, John A
Project Start
1997-09-15
Project End
2001-04-30
Budget Start
1999-09-01
Budget End
2001-04-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Mary Imogene Bassett Hospital
Department
Type
DUNS #
City
Cooperstown
State
NY
Country
United States
Zip Code
13326

  Publications

Blask, David E; Hill, Steven M; Dauchy, Robert T et al. (2011) 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. J Pineal Res 51:259-69
Sauer, Leonard A; Blask, David E; Dauchy, Robert T (2007) Dietary factors and growth and metabolism in experimental tumors. J Nutr Biochem 18:637-49
Dauchy, Robert T; Dauchy, Erin M; Davidson, Leslie K et al. (2007) 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. Comp Med 57:377-82
Smith, Laura C; Dauchy, Erin M; Dauchy, Robert T et al. (2006) Dietary fish oil deactivates a growth-promoting signaling pathway in hepatoma 7288CTC in Buffalo rats. Nutr Cancer 56:204-13
Dauchy, Erin M; Dauchy, Robert T; Davidson, Leslie K et al. (2006) 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. J Am Assoc Lab Anim Sci 45:38-44
Blask, David E; Dauchy, Robert T; Sauer, Leonard A (2005) Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal. Endocrine 27:179-88
Blask, David E; Brainard, George C; Dauchy, Robert T 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 Res 65:11174-84
Sauer, Leonard A; Dauchy, Robert T; Blask, David E et al. (2005) Eicosapentaenoic acid suppresses cell proliferation in MCF-7 human breast cancer xenografts in nude rats via a pertussis toxin-sensitive signal transduction pathway. J Nutr 135:2124-9
Dauchy, Robert T; Dauchy, Erin M; Sauer, Leonard A et al. (2004) Differential inhibition of fatty acid transport in tissue-isolated steroid receptor negative human breast cancer xenografts perfused in situ with isomers of conjugated linoleic acid. Cancer Lett 209:7-15
Sauer, Leonard A; Dauchy, Robert T; Blask, David E et al. (2004) Conjugated linoleic acid isomers and trans fatty acids inhibit fatty acid transport in hepatoma 7288CTC and inguinal fat pads in Buffalo rats. J Nutr 134:1989-97

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