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Document Type

Dissertation - University Access Only

Award Date

2014

Degree Name

Doctor of Philosophy (PhD)

Department

Health and Nutritional Sciences

First Advisor

Moul Dey

Abstract

It is well known that natural dietary compounds have therapeutic potential as functional food ingredients, nutraceuticals or dietary supplements against chronic human diseases such as inflammatory bowel disease (IBD), cancer and others. Phenethyl isothiocyanate (PEITC) belongs to the class of phytochemicals called isothiocyanates and is derived from cruciferous vegetables. Our previous research has shown promising antiinflammatory and chemo-preventive properties of PEITC. Effects of dietary compounds on site-specific histone modifications, which are key epigenetic regulators of gene expression impacting cancer etiology, remain relatively unexplored. The present study attempted to elucidate site-specific chemical changes to histone H3 in a gene-promoterspecific manner, associated with PEITC exposure in human colon tumor-derived epithelial cells. In addition, since PEITC is pro-apoptotic in various cancer cells and primary tumors, but its effect on cancer stem cells (CSC) remained unknown, this study also examined the effects of PEITC in attenuation of human cervical CSC proliferation and tumorigenesis. Therapeutic targeting of CSC has recently emerged as powerful strategy for cancer eradication. Overall, the results described in the following sections indicate that PEITC may offer a novel approach for improving the therapeutic outcomes in cancer patients. The bioactive dietary compound butyrate is a bacterial fermentation product of dietary fiber. The work presented here shows consuming resistant starch 4-(RS4)- enriched flour (30% v/v), a novel dietary fiber, has significant histone methylation changes (tri-methylations of lysine-27) in the colon tissues from KK.Cg-Ay/a mice that resembles the epigenetic modification is observed in human colon tumor-derived epithelial cells associated with sodium butyrate (NaB) treatment. Based on our findings, we conclude that RS4 has potential for inflammation and colon cancer prevention. Finally, genomic damage, epigenetic alterations and gut microbiota changes, all of which result from environmental factors can modulate gene expression and may lead to cancer. Aside from other individual factors such as age, gender, and physical activity, nutrition as the most important environmental factor has the ability to switch genes “on” or “off” differentially. Bioactive food components (BFCs) affect the modulation of DNA methylation and histone modifications in different cancer cells. Increased understanding of specific epigenetic alterations by dietary compounds may provide molecular predictors for improved preventative strategies for reducing the healthcare burden of cancer and other human diseases. This thesis presents a promising work of nutrient-gene interaction, which may provide potential chemo-preventive strategies for improving the therapeutic outcomes of IBD and colon cancer.

Library of Congress Subject Headings

Inflammatory bowel diseases
Colon (Anatomy) -- Cancer
Phytochemicals -- Therapeutic use
Bioactive compounds

Description

Includes bibliographical references (pages 121-138)

Format

application/pdf

Number of Pages

153

Publisher

South Dakota State University

Rights

In Copyright - Non-Commercial Use Permitted
http://rightsstatements.org/vocab/InC-NC/1.0/

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