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THE DIFFERENTIAL EFFECTS OF SELECTIVE COX-2 INHIBITORS ON CELL
PROLIFERATION AND INDUCED ER STRESS IN GLIOBLASTOMA AND
PANCREATIC CARCINOMA CELL LINES
by
Huan-Ching Chuang
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOCHEMISTRY & MOLECULAR BIOLOGY)
May 2008
Copyright 2008 Huan-Ching Chuang
Object Description
| Title | The differential effects of selective COX-2 inhibitors on cell proliferation and induced ER stress in glioblastoma and pancreatic carcinoma cell lines |
| Author | Chuang, Huan-Ching |
| Author email | florachuang@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2008-03-26 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-04-17 |
| Advisor (committee chair) | Schönthal, Axel H. |
| Advisor (committee member) |
Tokes, Zoltan A. Hong, Young Kwon |
| Abstract | Because many reports now challenge the notion that celecoxib (Celebrex®) execute its antitumor effect in the absence of COX-2 inhibitory activity, the aim of the project is to investigate COX-2 involvement with respect to its antitumor potential. We have studied two close structural analogs of celecoxib, DMC and UMC, which differentially display COX-2 inhibitory activity. UMC has COX-2 inhibitory function, while DMC has antitumor potential. In our results, DMC exhibited the most potent antitumor activity, while UMC was the least effective. During acute treatment, the three drugs and all tested cell lines were able to trigger endoplasmic reticulum stress, as indicated by the induction of CHOP, GRP78, and caspase-7 activation. Thus, we concluded that the antitumor activity of celecoxib is independent of COX-2 inhibitory activity and relies on the ability to trigger ER stress. This finding confirms previous studies and can be beneficial to anti-cancer therapy. |
| Keyword | Cyclooxygenase-2; reticulum stress; endoplasmic; CHO; caspase 7; GPR 78; survivin |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1144 |
| Rights | Chuang, Huan-Ching |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Chuang-20080417 |
| Archival file | uscthesesreloadpub_Volume14/etd-Chuang-20080417.pdf |
Description
| Title | Page 1 |
| Full text | THE DIFFERENTIAL EFFECTS OF SELECTIVE COX-2 INHIBITORS ON CELL PROLIFERATION AND INDUCED ER STRESS IN GLIOBLASTOMA AND PANCREATIC CARCINOMA CELL LINES by Huan-Ching Chuang A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOCHEMISTRY & MOLECULAR BIOLOGY) May 2008 Copyright 2008 Huan-Ching Chuang |
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