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Document Type

Campus-Only Access for Five (5) Years

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Animal Biotechnology & Biomedical Sciences

Year Degree Awarded

2015

Month Degree Awarded

September

First Advisor

Sallie Smith Schneider

Subject Categories

Cancer Biology | Cell Biology

Abstract

Obesity and breast cancer are two disease models that directly affect the United States population, as more than 35% of the adult population is obese [8], and more than 200,000 new cases of breast cancer are diagnosed in the United States per year [34]. Several diseases are associated with obesity including, cardiovascular disease, insulin resistance, increased inflammation and increased cancer risk [9,10]. Therefore it essential to understand the risks associated with obesity as well as to investigate possible preventive and/or therapeutic treatment strategies.

Rhodiola crenulata is a Tibetan plant that has been used in Eastern traditional medicine to relieve depression, anxiety, fatigue and to aid in high altitude biological adjustment [1]. Studies have also suggested that treatment with Rhodiola sp. and their components can improve glucose homeostasis in rodent models of insulin resistance[2-4] and inhibit tumor growth in various rodent models for cancer [5-7]. However, these studies have been plagued by the lack of strong mechanistic data.

The overall goal of this dissertation is to determine the mechanism by which R. crenulata affects glucose homeostasis in female mice subjected to Diet Induced Obesity (DIO) and to evaluate the effect of R. crenulata on 2 important cancer signaling pathways (canonical Wnt signaling and Estrogen receptor signaling) in breast cancer cells in vitro. In the work presented in this dissertation, we tested two main hypotheses; 1) 12 weeks of treatment with R. crenulata extract will decrease adiposity, improves glucose metabolism and obesity associated inflammation in female mice subjected to a high fat diet and 2) R. crenulata treatment will decrease Wnt/b-catenin signaling and Estrogen Receptor (ER) signaling in cancer cell lines in vitro. We used a wide variety of in vitro and in vivo techniques to test our hypotheses. Our results suggest that that R. crenulata can be beneficial for controlling insulin resistance and liver inflammation in a model for diet induced obesity. We also demonstrate two critical pathways in breast cancer cells that are controlled by R. crenulata. We show that treatment with a hydroalcoholic extract inhibits the canonical Wnt signaling pathway, which could explain some of the anti-neoplastic observations previously described by the Schneider lab. We also confirm that this R. crenulata extract contains estrogenic compounds; however despite this estrogenic activity, R.crenulata controlled proliferation and decreased tumorsphere growth and survival when cultures were treated for a longer period of time. Optimistically, the results from these studies will encourage further research on R. crenulata and possible usage as a preventive agent.

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