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Inhibition of colon carcinogenesis by stilbenoids and mechanisms of action

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Inhibition of colon carcinogenesis by stilbenoids and mechanisms of action
SubTitle
PartName
PartNumber
NonSort
Identifier (displayLabel = ); (invalid = )
ETD_2285
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000052141
Language (objectPart = )
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Food Science
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Plant polyphenols
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Stilbene
Subject (ID = SBJ-4); (authority = ETD-LCSH)
Topic
Antioxidants--Therapeutic use
Subject (ID = SBJ-5); (authority = ETD-LCSH)
Topic
Colon (Anatomy)--Cancer--Prevention
Abstract
Stilbenes are a class of compounds present in small fruits such as grapes and berries and are known to present diverse pharmacological properties which include cholesterol lowering, serum glucose regulation, controlling lifespan and anti-cancer activity. Resveratrol is one of the extensively studied stilbene. Pterostilbene (trans-3, 5-dimethoxy-4’-hydroxystilbene), a structural analog of resveratrol, is present in heartwood of the tree, Pterocarpus marsupium as well as in many small fruits such as blueberries.
In an attempt to study the effects of pterostilbene on colon carcinogenesis, we identified that pterostilbene inhibited expression of certain inflammatory genes in the colon and suppressed aberrant crypt foci formation in an azoxymethane (AOM)-induced model of colon carcinogenesis in rats. We also investigated the mechanism of anti-inflammatory action of pterostilbene using cultured HT-29 colon cancer cells. Our studies identified that the p38-ATF2 pathway was significantly inhibited by pterostilbene. More importantly, by silencing the expression of p38α isoform, there was significant reduction in iNOS and COX-2 induction. Interestingly, pterostilbene and the structurally similar compound, resveratrol, targeted different inflammatory pathways in HT-29 colon cells.
Pterostilbene given at 40 ppm of the diet of AOM-injected rats lowered the tumor multiplicity of non-invasive adenocarcinomas compared to the control diet. Pterostilbene lowered the β-catenin levels in HT-29 cells which can have implications in the action of the compound against cell proliferation. An evaluation of different structural analogs of pterostilbene revealed some compounds to have greater action than pterostilbene against colon cancer cells. Methoxylation, ester and amino modifications at the 4' position in the B ring conferred greater potency for the molecule against cell proliferation and inflammation in vitro. Amino substitutions and methoxy modifications with trans configuration reduced tumor burden significantly in the HT-29 xenograft tumor model in SCID mice. These compounds were present at higher levels in the serum of the animals compared to the levels of other compounds. In conclusion, stilbenoid class of compounds has promising effects against proliferation and inflammation in both in vivo and in vitro models of colon carcinogenesis.
PhysicalDescription
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electronic resource
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xii, 153 p. : ill.
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application/pdf
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Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references (p. 130-152)
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by Shiby Paul
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Paul
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Shiby
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1977-
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Shiby Paul
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Suh
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Nanjoo
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chair
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Advisory Committee
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Nanjoo Suh
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Yang
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Chung
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internal member
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Advisory Committee
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Chung S. Yang
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Ho
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Chi-Tang
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Chi-Tang Ho
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Rimando
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Agnes
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outside member
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Advisory Committee
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Agnes M Rimando
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
OriginInfo
DateCreated (point = ); (qualifier = exact)
2010
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2010-01
Place
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xx
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier (type = doi)
doi:10.7282/T31N8180
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

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The author owns the copyright to this work.
Copyright
Status
Copyright protected
Notice
Note
Availability
Status
Open
Reason
Permission or license
Note
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Paul
GivenName
Shiby
Role
Copyright Holder
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Place
DateTime
2009-12-09 17:26:44
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Name
Shiby Paul
Affiliation
Rutgers University. Graduate School - New Brunswick
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Author Agreement License
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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.
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Technical

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