Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.

Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.

Document Type

Campus-Only Access for Five (5) Years

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Food Science

Year Degree Awarded

2015

Month Degree Awarded

September

First Advisor

Hang Xiao

Subject Categories

Biochemical Phenomena, Metabolism, and Nutrition | Cancer Biology | Cell Biology | Natural Products Chemistry and Pharmacognosy | Other Food Science

Abstract

Among all the cancers, the death rate of colorectal cancer is one of the highest. Evidence from both murine xenograft model and human trials have shown cancer stem cells (CSCs) are responsible for the initiation, metastasis and recurrence of multiple cancers therefore targeting colorectal CSCs would be a promising chemo-preventive/ therapeutic strategy. Polymethoxyflavones including nobiletin (NBT) and 5-demethylatednobiletin (5DN) are exclusively found in citrus peels and have been shown to have anti-cancer effects. Our previous studies in the biotransformation and tissue distribution of NBT and 5DN have shown that in order to fuller evaluate the biological impact of those two PMFs, we also need to take into consideration of their metabolites. In this study, we examined the effects of these NBT and 5DN as well as their metabolites on tumor sphere formation, apoptosis and cell cycle distribution. Plus, we also made the initial attempt to investigate the possible mechanism(s) for the inhibitory effects we have observed. Our results showed that both NBT and its metabolites could inhibit the tumor sphere formation and induced apoptosis, with generally the metabolites having equivalent or stronger effects; On the other hand, M1 exerted the strongest inhibitory effect on colorectal CSCs compared to 5DN and other metabolites. Apoptosis, necroptosis as well as forcing CSCs to reenter the cell cycle from the quiescent states could be accounted to the overall inhibitory effects of NBT, 5DN and their metabolites.

With the achievement of our study, we will be able to better evaluate the overall efficacy of PMFs-based (NBT and 5DN) chemopreventive strategies on colorectal cancer, especially against colorectal CSCs

Share

COinS