The hypothesis addressed by this project is that selenium, vitamin E, and lycopene protect against prostate cancer development through their antioxidant activities. There are no definitive data about this from human studies. There are very few reports of experimental studies that tested this hypothesis, and those that did used models systems that do not involve oxidative stress mechanisms. Furthermore, there are no reports of studies that have investigated the probably critical synergisms that may exist between these antioxidants. Therefore, the purpose of this project is: (a) To address this hypothesis in an animal model of prostate carcinogenesis that does involve oxidative stress mechanisms; (b) To generate with this model data in support of the notion that antioxidant activity is a major mechanism by which selenium, vitamin E, and lycopene protect against prostate cancer; (d) To explore the efficacy and antioxidant activity of gamma-tocopherol. The project will use a unique animal model that is suitable to test chemopreventive activity of antioxidants and it will make a contribution to critically assessing the rationale for the SELECT trial; and (d) To determine the magnitude of the protective activity of these antioxidants individually and in combination to provide efficacy information in support of the design of prevention clinical trials.
The Specific Aims of the project are: (1) To determine the efficacy of selenium, vitamin E (alpha-tocopherol), and lycopene to prevent prostate cancer in NBL rats treated with estradiol & testosterone. This model importantly involves oxidative stress mechanisms. The antioxidants will be given in the diet at non-toxic doses comparable to those used in previous studies with prostate cancer models that do not involve oxidative stress. (2) To determine whether treatments with these antioxidants reduce oxidative stress parameters related to oxidation of DNA bases, lipid peroxidation, and inactivation or alteration of antioxidant enzymes. These parameters will be measured in the areas of the prostate of NBL rats where treatment with estradiol & testosterone induces cancer and preneoplastic lesions, and the effects observed will be related to the outcome of the efficacy studies of Specific Aim 1. Prostatic antioxidant levels will also be measured. (3) To determine the efficacy and antioxidant activity of gamma-tocopherol There are epidemiological indications that gamma-tocopherol has stronger protective effects against prostate cancer than alpha-tocopherol and the effects of gamma-tocopherol will be compared with those of the alpha-tocopherol studies of Aims 1 and 2. (4) To determine the efficacy of combination treatment with the three antioxidants to prevent prostate cancer in NBL rats treated with estradiol & testosterone and to determine whether these treatments reduce oxidative stress parameters. The observed effects will be compared with the outcome of the single agent studies of Aims 1 and 2.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA104334-01
Application #
6705901
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Perloff, Marjorie
Project Start
2004-02-01
Project End
2009-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
1
Fiscal Year
2004
Total Cost
$277,160
Indirect Cost
Name
New York University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
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Bosland, Maarten C; Ozten, Nur; Eskra, Jillian N et al. (2015) A Perspective on Prostate Carcinogenesis and Chemoprevention. Curr Pharmacol Rep 1:258-265
Özten, Nur; Schlicht, Michael; Diamond, Alan M et al. (2014) L-selenomethionine does not protect against testosterone plus 17?-estradiol-induced oxidative stress and preneoplastic lesions in the prostate of NBL rats. Nutr Cancer 66:825-34
Bosland, Maarten C (2013) A perspective on the role of estrogen in hormone-induced prostate carcinogenesis. Cancer Lett 334:28-33
Ozten-Kandas, Nur; Bosland, Maarten C (2011) Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence. J Carcinog 10:27
Ozten, Nur; Horton, Lori; Lasano, Salamia et al. (2010) Selenomethionine and alpha-tocopherol do not inhibit prostate carcinogenesis in the testosterone plus estradiol-treated NBL rat model. Cancer Prev Res (Phila) 3:371-80
Kanda?, Nur Ozten; Randolph, Carla; Bosland, Maarten C (2009) Differential effects of selenium on benign and malignant prostate epithelial cells: stimulation of LNCaP cell growth by noncytotoxic, low selenite concentrations. Nutr Cancer 61:251-64
Bosland, Maarten C (2006) Sex steroids and prostate carcinogenesis: integrated, multifactorial working hypothesis. Ann N Y Acad Sci 1089:168-76
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