2014_Apoptosis Induction of HT-29 Human Colorectal Adenocarcinoma Cells In-Vitro and Anti-Tumor Activity Against Colon Cancer of Newcastle Disease Virus Strains AF224O And V4-UPM

Bibliographic Details
Format: General Document
_version_ 1860797993083469824
building INTELEK Repository
collection Online Access
collectionurl https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3
copyright Copyright©PWB2025
country Malaysia
date 2015-04-14
format General Document
id 15334
institution UniSZA
internalnotes Sila masukkan subject wajib Dissertations, Academic. Terima kasih...
originalfilename APOPTOSIS INDUCTION OF HT-29 HUMAN COLORECTAL ADENOCARCINOMA CELLS IN-VITRO AND ANTI-TUMOR ACTIVITY AGAINST COLON CANCER OF NEWCASTLE DISEASE VIRUS STRAINS AF224O AND V4-UPM.pdf
person Rowa Mohammed Assayaghi
recordtype oai_dc
resourceurl https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15334
sourcemedia Server storage
Scanned document
spelling 15334 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15334 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 General Document Malaysia Library Staff (Top Management) Library Staff (Management) Library Staff (Support) Terengganu Faculty of Bio-resources & Food Industry English application/pdf 1.5 Server storage Scanned document Universiti Sultan Zainal Abidin UniSZA Private Access Universiti Sultan Zainal Abidin 166 SAMBox 2.4.24; modified using iTextSharp™ 5.5.10 ©2000-2016 iText Group NV (AGPL-version) APOPTOSIS INDUCTION OF HT-29 HUMAN COLORECTAL ADENOCARCINOMA CELLS IN-VITRO AND ANTI-TUMOR ACTIVITY AGAINST COLON CANCER OF NEWCASTLE DISEASE VIRUS STRAINS AF224O AND V4-UPM.pdf 2015-04-14 2014_Apoptosis Induction of HT-29 Human Colorectal Adenocarcinoma Cells In-Vitro and Anti-Tumor Activity Against Colon Cancer of Newcastle Disease Virus Strains AF224O And V4-UPM Apoptosis Rowa Mohammed Assayaghi Apoptosis HT-29 Cells Colorectal Adenocarcinoma Copyright©PWB2025 Newcastle disease virus (NDV) is a negative-sense single stranded RNA virus of the Paramyxoviridae family that causes severe disease in several avian species. Several NDV strains have been investigated for their anti-cancer effects because it can replicate up to 10000 times better in human neoplastically transformed cells than in most normal human cells. Since treatment of cancer patient with chemo-radiotherapy caused severe side effects due to cltotoxic effbcts towards normal tissues which often is resulting in morbidity. NDV strains AF2240 and V4-UPM were shown to be cyolyic against various cancer cells in-vitro and very effective as antileukemic agents. Therefore in this thesis both NDV strains were evaluated for their cl,tolytic effects on human colon cancer cells in-vitro and ln-vpo effects against chemical induced colon cancer in rats. In this study, the c),tol,,tic effects and apoptosis induction ofNDV strains AF2240 and V4-UPM against HT-29 human colorectal adenocarcinoma cells were carried out. Moreover effects ofboth virus strains on the abenant crypt foci (ACF) and some colon cancer marker expressions of induced colon cancer in-vivo were also studied. The CDso values for cytol),tic effects of NDV strains AF2240 and strain V4-UPM on HT-29 by using MTT assay were 16.0 and 33.0 HAU /mL, respectively. However, the same titers of virus strains did not give significant cltol),tic effects on the normal mouse fibroblasts (3T3) cells. Apoptosis and necrosis cell death modes were evaluated base on the morphological changes observed under the phase contrast light and fluorescent microscopies after staining with acridine orange and propidium iodide (AO/pl). Both NDV strains induced apoptosis cell death to the HT-29 cells. The percentage of apoptotic cells were increased in the time dependent manner as compared to viable and necrotic cells. The intrinsic and extrinsic apoptosis pathways were determined by assaying the related caspases activities and studying the expression of some apoptotic genes. A significant activation of caspase-g, an initiator caspase for the intrinsic pathway compared to caspase-8 was observed. Moreover, RT-PCR results showed Bax expression was up-regulated in HT-29 cells that treated with both NDV strains while down-regulated was observed in non-treated HT-29 cells. In contrast, Bcl-2 expression was up-regulated in non-treated cells and down-regulated in HT-29 cells that were treated with both NDV strains. The results suggest that NDv-induced apoptosis through intrinsic (mitochondrial) pathway of HT-29 human colorectal adenocarcinoma cells. Anti-tumor activity of NDV strains AF 2240 and V4-UPM were evaluated in-vivo by different doses of NDV on the development of aberrant crypt foci (ACF) in Sprague Dawley rats initiated with the colon carcinogen Azox).rnethane (AOM). The total number and crypt multiplicity of ACF were significantly decreased in NDV treated groups as compared to non-treated rats. The efficacy of the combination treatrnent of NDV on the development of ACF in rats' colon was also investigated. H istopatholgical study was carried out to confirm results of methytene blue method. The severe dysplasia of ACF was only found and observed in the non-treated group, while mild and moderate dysplasia of ACF were exhibited in other groups. The number and degree of dysplasia of ACF were significantly decreased in the combination treatment of NDV and 5-FU, 5-FU-only and high doses NDV. The interaction between COX-l and COX-2 genes in rats that were treated with diflerent doses of NDV strains and 5 FU was elucidated. COX-2 expression was up-regulated in positive control and low doses NDV groups compared to other groups. The above results have confirmed that NDV strains AF 2240 and V4-UPM were cytolltic against HT-29 human colorectal adenocarcinoma cells in-vitro and very effective in reducing ACF induced colon cancer in-vivo. Dissertations, Academic Sila masukkan subject wajib Dissertations, Academic. Terima kasih... Thesis
spellingShingle 2014_Apoptosis Induction of HT-29 Human Colorectal Adenocarcinoma Cells In-Vitro and Anti-Tumor Activity Against Colon Cancer of Newcastle Disease Virus Strains AF224O And V4-UPM
state Terengganu
subject Apoptosis
Dissertations, Academic
summary Newcastle disease virus (NDV) is a negative-sense single stranded RNA virus of the Paramyxoviridae family that causes severe disease in several avian species. Several NDV strains have been investigated for their anti-cancer effects because it can replicate up to 10000 times better in human neoplastically transformed cells than in most normal human cells. Since treatment of cancer patient with chemo-radiotherapy caused severe side effects due to cltotoxic effbcts towards normal tissues which often is resulting in morbidity. NDV strains AF2240 and V4-UPM were shown to be cyolyic against various cancer cells in-vitro and very effective as antileukemic agents. Therefore in this thesis both NDV strains were evaluated for their cl,tolytic effects on human colon cancer cells in-vitro and ln-vpo effects against chemical induced colon cancer in rats. In this study, the c),tol,,tic effects and apoptosis induction ofNDV strains AF2240 and V4-UPM against HT-29 human colorectal adenocarcinoma cells were carried out. Moreover effects ofboth virus strains on the abenant crypt foci (ACF) and some colon cancer marker expressions of induced colon cancer in-vivo were also studied. The CDso values for cytol),tic effects of NDV strains AF2240 and strain V4-UPM on HT-29 by using MTT assay were 16.0 and 33.0 HAU /mL, respectively. However, the same titers of virus strains did not give significant cltol),tic effects on the normal mouse fibroblasts (3T3) cells. Apoptosis and necrosis cell death modes were evaluated base on the morphological changes observed under the phase contrast light and fluorescent microscopies after staining with acridine orange and propidium iodide (AO/pl). Both NDV strains induced apoptosis cell death to the HT-29 cells. The percentage of apoptotic cells were increased in the time dependent manner as compared to viable and necrotic cells. The intrinsic and extrinsic apoptosis pathways were determined by assaying the related caspases activities and studying the expression of some apoptotic genes. A significant activation of caspase-g, an initiator caspase for the intrinsic pathway compared to caspase-8 was observed. Moreover, RT-PCR results showed Bax expression was up-regulated in HT-29 cells that treated with both NDV strains while down-regulated was observed in non-treated HT-29 cells. In contrast, Bcl-2 expression was up-regulated in non-treated cells and down-regulated in HT-29 cells that were treated with both NDV strains. The results suggest that NDv-induced apoptosis through intrinsic (mitochondrial) pathway of HT-29 human colorectal adenocarcinoma cells. Anti-tumor activity of NDV strains AF 2240 and V4-UPM were evaluated in-vivo by different doses of NDV on the development of aberrant crypt foci (ACF) in Sprague Dawley rats initiated with the colon carcinogen Azox).rnethane (AOM). The total number and crypt multiplicity of ACF were significantly decreased in NDV treated groups as compared to non-treated rats. The efficacy of the combination treatrnent of NDV on the development of ACF in rats' colon was also investigated. H istopatholgical study was carried out to confirm results of methytene blue method. The severe dysplasia of ACF was only found and observed in the non-treated group, while mild and moderate dysplasia of ACF were exhibited in other groups. The number and degree of dysplasia of ACF were significantly decreased in the combination treatment of NDV and 5-FU, 5-FU-only and high doses NDV. The interaction between COX-l and COX-2 genes in rats that were treated with diflerent doses of NDV strains and 5 FU was elucidated. COX-2 expression was up-regulated in positive control and low doses NDV groups compared to other groups. The above results have confirmed that NDV strains AF 2240 and V4-UPM were cytolltic against HT-29 human colorectal adenocarcinoma cells in-vitro and very effective in reducing ACF induced colon cancer in-vivo.
title 2014_Apoptosis Induction of HT-29 Human Colorectal Adenocarcinoma Cells In-Vitro and Anti-Tumor Activity Against Colon Cancer of Newcastle Disease Virus Strains AF224O And V4-UPM
title_full 2014_Apoptosis Induction of HT-29 Human Colorectal Adenocarcinoma Cells In-Vitro and Anti-Tumor Activity Against Colon Cancer of Newcastle Disease Virus Strains AF224O And V4-UPM
title_fullStr 2014_Apoptosis Induction of HT-29 Human Colorectal Adenocarcinoma Cells In-Vitro and Anti-Tumor Activity Against Colon Cancer of Newcastle Disease Virus Strains AF224O And V4-UPM
title_full_unstemmed 2014_Apoptosis Induction of HT-29 Human Colorectal Adenocarcinoma Cells In-Vitro and Anti-Tumor Activity Against Colon Cancer of Newcastle Disease Virus Strains AF224O And V4-UPM
title_short 2014_Apoptosis Induction of HT-29 Human Colorectal Adenocarcinoma Cells In-Vitro and Anti-Tumor Activity Against Colon Cancer of Newcastle Disease Virus Strains AF224O And V4-UPM
title_sort 2014_apoptosis induction of ht-29 human colorectal adenocarcinoma cells in-vitro and anti-tumor activity against colon cancer of newcastle disease virus strains af224o and v4-upm