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THE CHEMOPREVENTIVE EFFECT OF POLYMETHOXYFLAVONES: TARGETING THE COLORECTAL CANCER STEM CELLS

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dc.contributor.advisorHang Xiao
dc.contributor.authorXu, Fei
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.date2024-03-27T17:38:34.000
dc.date.accessioned2024-04-26T16:10:25Z
dc.date.available2024-04-26T16:10:25Z
dc.date.submittedSeptember
dc.date.submitted2015
dc.description.abstractAmong 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
dc.description.degreeDoctor of Philosophy (PhD)
dc.description.departmentFood Science
dc.identifier.doihttps://doi.org/10.7275/7535387.0
dc.identifier.orcidN/A
dc.identifier.urihttps://hdl.handle.net/20.500.14394/19759
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1548&context=dissertations_2&unstamped=1
dc.source.statuspublished
dc.subjectColorectal cancer
dc.subjectPolymethoxyflavones
dc.subjectCancer stem cell
dc.subjectMetabolites
dc.subjectNobiletin
dc.subject5-demethylnobiletin
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectCancer Biology
dc.subjectCell Biology
dc.subjectNatural Products Chemistry and Pharmacognosy
dc.subjectOther Food Science
dc.titleTHE CHEMOPREVENTIVE EFFECT OF POLYMETHOXYFLAVONES: TARGETING THE COLORECTAL CANCER STEM CELLS
dc.typeopenaccess
dc.typearticle
dc.typedissertation
digcom.contributor.authorisAuthorOfPublication|email:xufei5055@gmail.com|institution:University of Massachusetts Amherst|Xu, Fei
digcom.identifierdissertations_2/535
digcom.identifier.contextkey7535387
digcom.identifier.submissionpathdissertations_2/535
dspace.entity.typePublication
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