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United States Department of Agriculture

Agricultural Research Service

Related Topics

Research Project: DIETARY COMPONENTS AND CANCER PREVENTION

Location: Jean Mayer Human Nutrition Research Center On Aging

2012 Annual Report


1a. Objectives (from AD-416):
LAB: VITAMINS & CARCINOGENESIS 1. To define the role that availability of each of the one-carbon nutrients plays in determining the risk of common cancers and to determine the nature of the interactions between these nutrients in this regard. 2. Determine how genetic differences interact with dietary antagonists of one-carbon nutrients in determining cancer risk. (PDRAM NAA09). 3. To determine how obesity enhances the risk of cancer, to find means of ameliorating this risk, and to define other factors that interact with obesity to further modify its effects. LAB: NUTRITION & CANCER 1. Determine whether high fat diet induced non-alcoholic steatohepatitis is a promoting factor in hepatic carcinogenesis. 2. Determine whether dietary lycopene will protect against high fat diet promoted liver cancer development.


1b. Approach (from AD-416):
LAB: VITAMINS & CARCINOGENESIS Appropriate alterations in dietary and nutritional habits have an important role to play in cancer prevention. The nutrients involved in one-carbon metabolism (methionine, choline and the B-vitamins, folate, B12, B6, and B2), as well as obesity, have drawn considerable attention in this regard and are the focus of this laboratory. Our mission is to examine the complex roles that obesity and these 1-carbon nutrients play in modifying metabolic and genetic pathways that lead to human carcinogenesis and thereby define the means by which cancers can be nutritionally prevented. The program of research emphasizes how dietary intake interacts with genetic background to modify molecular and signaling pathways which alter the development of cancers and to examine how other exogenous factors, such as alcohol consumption also play a role. The laboratory focuses on colorectal cancer and breast cancer and utilizes animal studies, cell culture studies, and human studies to accomplish our research goals. LAB: NUTRITION & CANCER We will use both high fat diet-induced nonalcoholic steatohepatitis (NASH) rats and genetically-induced obese mice with injections of liver-specific carcinogen, diethylnitrosamine, followed by treatment with tomato extract or lycopene for both short and long durations. We will focus on the role of the stress-activated protein c-Jun-NH2-kinase (JNK) signaling, a key component mediating the high fat-induced oxidative stress and inflammatory processes, in response to tomato extract and lycopene supplementation on both cell proliferation/apoptosis, inflammation and premalignant and malignant lesions in obesity related hepatic tumorigenesis. We will complement animal study with cell culture studies (e.g., use siRNA silencing of JNK) using human hepatocyte lines and liver cancer cells to facilitate mechanistic studies to determine the contribution of the JNK signaling pathway to lycopene action. Since adiposity contributes to the increased incidence and/or death from liver cancer, we will examine metabolic alteration, including insulin resistance, and pro-inflammatory signaling in intra-abdominal fat tissue and its potential contribution to hepatic carcinogenesis. Once we establish that there is an association between metabolic alteration and hepatic carcinogenesis, we will examine insulin and insulin growth factors (IGF-I/IGF-II) signaling cascades and address their differential activation in NASH and its related hepatic carcinogenesis, as well as potential actions of tomato extract and lycopene prevention against the onset of high fat diet/obesity-related liver disease.


3. Progress Report:
This progress report includes the work of two subordinate projects at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress reposrts, see 1950-51000-074-01S (One-carbon nutrients in the prevention of cancer) and 1950-51000-074-02S (Nutritional determinants of non-alcoholic steatohepatitis in hepatic carcinogeneis).


4. Accomplishments


Review Publications
Liu, Z., Brooks, R., Ciappio, E., Kim, S., Crott, J., Bennett, G., Greenberg, A., Mason, J. 2011. Diet-induced obesity elevates colonic TNF-alpha in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer. Journal of Nutritional Biochemistry. Available: www.sciencedirect.com.

Mason, J., Crott, J., Ciappio, E. 2011. Maternal one-carbon nutrient intake and cancer risk in offspring. Nutrition Reviews. 69(10):561-571.

Liu, Z., Ciappio, E.D., Crott, J.W., Brooks, R.S., Nesvet, J., Smith, D.E., Choi, S., Mason, J.B. 2011. Combined inadequacies of multiple B-vitamins amplify colonic Wnt-signaling and promote intestinal tumorigenesis in BAT-LacZxApc1368N mice. Journal of Federation of American Societies for Experimental Biology. 25(9):3136-3145.

Sie, K., Medine, A., Van Weel, J., Sohn, K., Choi, S., Croxford, R., Kim, Y. 2011. Effect of maternal and postweaning folic acid supplementation on colorectal cancer risk in the offspring. Gut. 60:1687-1694.

Crott, J., Ciappio, E., Liu, Z., Brooks, R., Mason, J., Bronson, R.T. 2011. Maternal B-vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis in Apc+/1638N mouse offspring. Gut. 60(12):1695-1702.

Tang, F., Pai, M., Wang, X. 2011. Consumption of lycopene inhibits the growth and progression of colon cancer in a mouse xenograft model. Journal of Agricultural and Food Chemistry. 59(16):9011-9021.

Tomaszewski, J.J., Cummings, J.L., Parwani, A., Dhir, R., Mason, J.B., Nelson, J.B., Bachich, D.J., O'Keefe, D.S. 2011. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate. The Prostate Journal. 71(12):1287-1293.

Liu, C., Bronson, R.T., Russell, R., Wang, X. 2011. Beta-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage and squamous metaplasia in ferrets. Cancer Prevention Research. PMID:21421799.

Kim, Y., Chongviriyaphana, N., Liu, C., Russel, R., Wang, X. 2012. Combined alpha-tocopherol and ascorbic acid protects against smoke-induced lung squamous metaplasia in ferrets. Lung Cancer. 75:15-23.

Chung, J., Koo, K., Lian, F., Hu, K., Ernst, H., Wang, X. 2012. Apo-10'-lycopenoic acid, a lycopene 1 metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice. Journal of Nutrition. 142(3):405-410.

Tao, M., Mason, J., Marian, C., Mccann, S., Platek, M., Millen, A., Ambrosone, C., Edge, S., Krishan, S., Trevisan, M., Shields, P., Freudenheim, J. 2011. Promoter methylation of E-cadherin, p16, and RAR-beta(2) genes in breast tumors and dietary intake of nutrients important in one-carbon metabolism. Nutrition and Cancer. 63(7):1143-1150.

Last Modified: 10/18/2017
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