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Inhibition of lung tumorigenesis and cancer cell growth by EGCG and other chemopreventive agents
Descriptive
TitleInfo
Title
Inhibition of lung tumorigenesis and cancer cell growth by EGCG and other chemopreventive agents
Name
(type = personal)
NamePart
(type = family)
Jin
NamePart
(type = given)
Huanyu
NamePart
(type = date)
1983-
DisplayForm
Huanyu Jin
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
yang
NamePart
(type = given)
chung s
DisplayForm
chung s yang
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Conney
NamePart
(type = given)
Allan H
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Allan H Conney
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Suh
NamePart
(type = given)
Nanjoo
DisplayForm
Nanjoo Suh
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Wagner
NamePart
(type = given)
George C
DisplayForm
George C Wagner
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
(type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB)
school
TypeOfResource
Text
Genre
(authority = marcgt)
theses
OriginInfo
DateCreated
(qualifier = exact)
2013
DateOther
(qualifier = exact);
(type = degree)
2013-10
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Lung cancer is the leading cause of cancer death in the United States and the most commonly diagnosed cancer worldwide and smoking is a key risk factor of lung cancer. The purpose of this thesis study is to characterize the mechanisms of 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone (NNK)-induced lung tumorigenesis in A/J mice and the inhibitory activities of (−)-epigallocatechin-3-gallate (EGCG) and other chemopreventive agents including tocopherols, myo-inositol and atorvastatin. DNA methyltransferase 1 (DNMT1), a key enzyme mediating DNA methylation, is known to be activated in cancers, including the mouse lung tumors induced by NNK. However, it is not known how NNK treatment affects the DNMT1 expression. We found that administration of NNK to A/J mice caused elevation of DNMT1 in bronchial epithelial cells at days 1-14. DNMT1 elevation at days 1 and 3 was accompanied by an increase in -H2AX and phospho-AKT (p-AKT), which has been shown to stabilize DNMT1 at the protein level by inhibiting the ubiquitination of DNMT1. Induction of O6-methylguanine, cyclooxygenase-2 (COX-2), superoxide dismutase (SOD) and catalase by NNK treatment was also observed at days 1-14. DNMT1 expression decreased to lower levels at weeks 5-20 in lung tissues, but was highly elevated in lung tumors at week 20. In concordance with DNMT1 elevation, promoter hypermethylation of tumor suppressor genes Cdh13, Prdm2 and Runx3 was observed in lung tissues at day 3 and in lung tumors at week 20. EGCG (0.4% in diet) treatment attenuated the induction of DNMT1, p-AKT and γ-H2AX at days 1 and 3 and inhibited lung tumorigenesis. EGCG, γ-tocopherol-rich mixture of tocopherols (γ-TmT) and myo-inositol significantly reduced tumor multiplicity and tumor size in the NNK model. The EGCG-generated reactive oxygen species (ROS) caused cell growth inhibition and induction of apoptosis and oxidative DNA damage in vitro. Apoptosis and oxidative DNA damage were also induced in lung tumors by EGCG treatment at the tumor stage. Short-term γ-TmT treatment at the tumor stage induced antioxidant enzymes SOD and glutathione peroxidase. Myo-inositol treatment significantly reduced the level of p-c-Jun in lung tumors.
Subject
(authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_4884
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xv, 150 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Huanyu Jin
Subject
(authority = ETD-LCSH)
Topic
Lungs--Cancer--Research
Subject
(authority = ETD-LCSH)
Topic
Methylation
Subject
(authority = ETD-LCSH)
Topic
Methyltransferases
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3W9576R
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Jin
GivenName
Huanyu
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2013-06-19 10:26:26
AssociatedEntity
Name
Huanyu Jin
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2013-10-31
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = end)
2015-10-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2015.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
(ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem
(VERSION = 5.1)
windows xp
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