Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells

Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells

2',3'-epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol are two bioactive compounds isolated from the leaves of Mzcromelum minutum. The cytotoxic effect of the compounds was tested on a variety of human cell lines respectively using MTT assay. They were found to be...

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Main Author: Tan, Boon Keat
Format: Thesis
Language:English
English
Published: 2006
Subjects:
Diseases - Causes and theories of causation
Online Access:http://psasir.upm.edu.my/id/eprint/6777/1/IB_2006_5.pdf
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spelling my-upm-ir.67772023-11-08T07:55:46Z Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells 2006-03 Tan, Boon Keat 2',3'-epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol are two bioactive compounds isolated from the leaves of Mzcromelum minutum. The cytotoxic effect of the compounds was tested on a variety of human cell lines respectively using MTT assay. They were found to be most sensitive against human T-lymphoblastic leukemia cells (CEM-SS). The inhibition effect of 2',3'-epoxyisocapnolactone and 8- hydroxyisocapnolactone-2',3'-diol at 50% of cell population (ICso) was found to be 4.6 pg/ml (13.5 pM) and 3 pdml (7.8 pM) on CEM-SS cells, respectively. Besides that, the inhibitor effect of the compounds on other human cells were found to be 13.4 pdml(39.2 pM) and 9.0 pdml(23.9 pM) on cervical carcinoma cells (HeLa), 14.2 pg/ml (41.5 pM) and 7.7 pdml (20.5 pM) on colon adenocarcinoma cells (HT29), 7.4 pg/ml (21.6 pM) and 5.9 pdml (1 5.7 pM) on hepatocarcinoma cells (HepG2), 6.5 pglml (19.0 pM) and 7.1 pg/ml(18.9 pM) on transform liver cells (Chang). For comparative purposes, the ICW of several clinical cytotoxic drugs against CEM-SS cells were determined. The inhibitor effect of the compounds were more significant compared with methotrexate [ICm = >30 pg/ml (66.1 pM)], cytosine arabinoside [IC5o = >30 pg/ml (123.5 pM)] and colchicines [IC50 = 8 pglml (20.1 pM)] The compounds also shown near similar ICso concentration as compare with cis-diamine dichloroplatinum [IC50 = 3 pg/ml (10.1 pM)], vinorelbine [IC50 = 3 pg/ml (3.9 pM)] and doxorubicin [IC5o = 2.4 pg/ml (4.1 pM)]. Furthermore, from proliferation assay study, the compounds were significantly inhibiting the proliferation of cells at ICso value. From the morphological observation and agarose gel electrophoresis, apoptosis of the compounds on CEM-SS cells was determined. By using phase contrast, fluorescence and electron microcopies, observation on morphological alterations indicating apoptosis was evaluated. From DNA fragmentation, Acridine orange and Propidium iodide staining and DNA content analyses, the compounds were confirmed to have ability in promoting apoptosis. However, the percentage of apoptosis induced is low and the event is time-dependent. At high concentration of 10 pg/m, 2',3'- epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol induced necrosis. Furthermore, 8-hydroxyisocapnolactone-2',3'-diol also exhibited better cytotoxicity compared to 2',3'-epoxyisocapnolactone. The induction time for apoptosis by 8- hydroxyisocapnolactone-2',3'-diol in CEM-SS is earlier than 2',3'-epoxyisocapnolactone, which is 4 hours and 12 hours after treatment. Based on the results obtained, 2',3'- epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol are able to induced apoptosis. Diseases - Causes and theories of causation 2006-03 Thesis http://psasir.upm.edu.my/id/eprint/6777/ http://psasir.upm.edu.my/id/eprint/6777/1/IB_2006_5.pdf text en public masters Universiti Putra Malaysia Diseases - Causes and theories of causation Institute Bioscience Ali, Abdul Manaf English
institution Universiti Putra Malaysia
collection PSAS Institutional Repository
language English
English
advisor Ali, Abdul Manaf
topic Diseases - Causes and theories of causation
spellingShingle Diseases - Causes and theories of causation


Tan, Boon Keat
Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells
description 2',3'-epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol are two bioactive compounds isolated from the leaves of Mzcromelum minutum. The cytotoxic effect of the compounds was tested on a variety of human cell lines respectively using MTT assay. They were found to be most sensitive against human T-lymphoblastic leukemia cells (CEM-SS). The inhibition effect of 2',3'-epoxyisocapnolactone and 8- hydroxyisocapnolactone-2',3'-diol at 50% of cell population (ICso) was found to be 4.6 pg/ml (13.5 pM) and 3 pdml (7.8 pM) on CEM-SS cells, respectively. Besides that, the inhibitor effect of the compounds on other human cells were found to be 13.4 pdml(39.2 pM) and 9.0 pdml(23.9 pM) on cervical carcinoma cells (HeLa), 14.2 pg/ml (41.5 pM) and 7.7 pdml (20.5 pM) on colon adenocarcinoma cells (HT29), 7.4 pg/ml (21.6 pM) and 5.9 pdml (1 5.7 pM) on hepatocarcinoma cells (HepG2), 6.5 pglml (19.0 pM) and 7.1 pg/ml(18.9 pM) on transform liver cells (Chang). For comparative purposes, the ICW of several clinical cytotoxic drugs against CEM-SS cells were determined. The inhibitor effect of the compounds were more significant compared with methotrexate [ICm = >30 pg/ml (66.1 pM)], cytosine arabinoside [IC5o = >30 pg/ml (123.5 pM)] and colchicines [IC50 = 8 pglml (20.1 pM)] The compounds also shown near similar ICso concentration as compare with cis-diamine dichloroplatinum [IC50 = 3 pg/ml (10.1 pM)], vinorelbine [IC50 = 3 pg/ml (3.9 pM)] and doxorubicin [IC5o = 2.4 pg/ml (4.1 pM)]. Furthermore, from proliferation assay study, the compounds were significantly inhibiting the proliferation of cells at ICso value. From the morphological observation and agarose gel electrophoresis, apoptosis of the compounds on CEM-SS cells was determined. By using phase contrast, fluorescence and electron microcopies, observation on morphological alterations indicating apoptosis was evaluated. From DNA fragmentation, Acridine orange and Propidium iodide staining and DNA content analyses, the compounds were confirmed to have ability in promoting apoptosis. However, the percentage of apoptosis induced is low and the event is time-dependent. At high concentration of 10 pg/m, 2',3'- epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol induced necrosis. Furthermore, 8-hydroxyisocapnolactone-2',3'-diol also exhibited better cytotoxicity compared to 2',3'-epoxyisocapnolactone. The induction time for apoptosis by 8- hydroxyisocapnolactone-2',3'-diol in CEM-SS is earlier than 2',3'-epoxyisocapnolactone, which is 4 hours and 12 hours after treatment. Based on the results obtained, 2',3'- epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol are able to induced apoptosis.
format Thesis
qualification_level Master's degree
author Tan, Boon Keat
author_facet Tan, Boon Keat
author_sort Tan, Boon Keat
title Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells
title_short Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells
title_full Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells
title_fullStr Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells
title_full_unstemmed Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells
title_sort induction of apoptosis by 2', 3’-epoxyisocapnolactone and 8-hydroxyisocapnolactone-2', 3’- diol isolated from micromelum minutum in human t-lymphocyte leukemia cem-ss cells
granting_institution Universiti Putra Malaysia
granting_department Institute Bioscience
publishDate 2006
url http://psasir.upm.edu.my/id/eprint/6777/1/IB_2006_5.pdf
_version_ 1783725777987043328

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