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Involvement of the 5-lipoxygenase pathway in oro-esophageal carcinogenesis and chemopreventive effects of ziIeuton and green tea catechins
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Title
Involvement of the 5-lipoxygenase pathway in oro-esophageal carcinogenesis and chemopreventive effects of ziIeuton and green tea catechins
Name
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NamePart
(type = family)
Sood
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(type = given)
Sandeep
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Sandeep Sood
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author
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(type = personal)
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(type = family)
Yang
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(type = given)
Chung S.
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Advisory Committee
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Chung S. Yang
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chair
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(type = family)
Chen
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Xiaoxin
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Advisory Committee
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Xiaoxin Chen
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Ho
NamePart
(type = given)
Chi Tang
Affiliation
Advisory Committee
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Chi Tang Ho
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(authority = RULIB)
internal member
Name
(type = personal)
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(type = family)
Reuhl
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Kenneth
Affiliation
Advisory Committee
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Kenneth Reuhl
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(authority = RULIB)
outside member
Name
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NamePart
Rutgers University
Role
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(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School-New Brunswick
Role
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(authority = RULIB)
school
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Text
Genre
(authority = marcgt)
theses
OriginInfo
DateCreated
(qualifier = exact)
2007
DateOther
(qualifier = exact);
(type = degree)
2007
Language
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(authority = ISO 639-3:2007);
(type = text)
English
PhysicalDescription
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electronic
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application/pdf
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text/xml
Extent
xii, 121 pages
Abstract
(type = abstract)
Oral and esophageal squamous cell carcinomas (SCC) are common neoplasms worldwide, especially in developing countries. Aberrant arachidonic acid (AA) metabolism, involving both the cyclooxygenase (Cox) and lipoxygenase (Lox) pathways has been suggested to play an important role in the development of inflammation and associated carcinogenesis.
The primary aim of this study was to evaluate the role of 5-Lox in oro-esophageal carcinogenesis. Zileuton, a 5-Lox inhibitor, was evaluated for its effect, in short- and long-term studies on oral carcinogenesis using the 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster cheek pouch model. In the short-term study, zileuton significantly inhibited aberrant AA metabolism and cell hyperproliferation and in the long-term experiment it suppressed the incidence of visible tumors as well as the SCC. Zileuton and green tea catechins, alone and in combination, were also evaluated in 4-nitroquinoline-1-oxide (4-NQO)-induced oro-esophageal carcinogenesis in mice. In the first experiment, 4-NQO was administered to A/J mice (wild-type and p53A135V mutant) in drinking water for 8 weeks, followed by zileuton (1000 ppm in diet) or polyphenon E (PPE, 0.6% in drink) for another 16 weeks. Zileuton significantly reduced the overall incidence of SCC in tongue, esophagus and forestomach in wild-type A/J mice. PPE only significantly reduced carcinogenesis in the tongue of p53A135V mutant mice. Both agents suppressed cell proliferation and induced apoptosis, while only zileuton significantly reduced the mast cells density in cancer tissues of tongue and esophagus. In the second experiment, 4-NQO was administered to C57BL/6J mice in drinking water for 12 weeks, followed by zileuton (500, 1000 and 2000 ppm in diet) and epigallocatechin-3-gallate (EGCG, 0.16% and 0.32% in drink) alone or in combination (500 ppm zileuton and 0.16% EGCG) for another 16 weeks. Both agents were able to significantly inhibit tongue cancer. Zileuton and EGCG inhibited overall carcinogenesis, though only the effect of the former was dose-dependent. An additive effect was observed in the combination group in inhibiting the tongue and overall cancer incidence. In summary, we report here that 5-Lox is involved in the pathogenesis of oro-esophageal carcinogenesis and its inhibitors, zileuton and green tea catechins, elicit chemopreventive activity in animal models.
The primary aim of this study was to evaluate the role of 5-Lox in oro-esophageal carcinogenesis. Zileuton, a 5-Lox inhibitor, was evaluated for its effect, in short- and long-term studies on oral carcinogenesis using the 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster cheek pouch model. In the short-term study, zileuton significantly inhibited aberrant AA metabolism and cell hyperproliferation and in the long-term experiment it suppressed the incidence of visible tumors as well as the SCC. Zileuton and green tea catechins, alone and in combination, were also evaluated in 4-nitroquinoline-1-oxide (4-NQO)-induced oro-esophageal carcinogenesis in mice. In the first experiment, 4-NQO was administered to A/J mice (wild-type and p53A135V mutant) in drinking water for 8 weeks, followed by zileuton (1000 ppm in diet) or polyphenon E (PPE, 0.6% in drink) for another 16 weeks. Zileuton significantly reduced the overall incidence of SCC in tongue, esophagus and forestomach in wild-type A/J mice. PPE only significantly reduced carcinogenesis in the tongue of p53A135V mutant mice. Both agents suppressed cell proliferation and induced apoptosis, while only zileuton significantly reduced the mast cells density in cancer tissues of tongue and esophagus. In the second experiment, 4-NQO was administered to C57BL/6J mice in drinking water for 12 weeks, followed by zileuton (500, 1000 and 2000 ppm in diet) and epigallocatechin-3-gallate (EGCG, 0.16% and 0.32% in drink) alone or in combination (500 ppm zileuton and 0.16% EGCG) for another 16 weeks. Both agents were able to significantly inhibit tongue cancer. Zileuton and EGCG inhibited overall carcinogenesis, though only the effect of the former was dose-dependent. An additive effect was observed in the combination group in inhibiting the tongue and overall cancer incidence. In summary, we report here that 5-Lox is involved in the pathogenesis of oro-esophageal carcinogenesis and its inhibitors, zileuton and green tea catechins, elicit chemopreventive activity in animal models.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references (p. 65-78).
Subject
(authority = RUETD)
Topic
Food Science
Subject
(authority = ETD-LCSH)
Topic
Green tea
Subject
(authority = ETD-LCSH)
Topic
Esophagus
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Identifier
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.13736
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ETD_193
Identifier
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doi:10.7282/T3542P1H
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Genre
(authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
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Copyright protected
Availability
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Open
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Sandeep Sood
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Copyright holder
Affiliation
Rutgers University. Graduate School-New Brunswick
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Non-exclusive ETD license
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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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