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Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines

An increasing number of terpenoids that possess anticancer activity has attracted researchers' attention worldwide. This study focused on how selected terpenoids affect the cell proliferation, morphology alteration and the mechanism of cell death in breast cancer cells. The results in anti-prol...

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Main Author: Robert, Alex Walzico
Format: Thesis
Language:English
English
Published: 2020
Subjects:
QP501-801 Animal biochemistry
Online Access:https://eprints.ums.edu.my/id/eprint/42603/1/24%20PAGES.pdf
https://eprints.ums.edu.my/id/eprint/42603/2/FULLTEXT.pdf
https://eprints.ums.edu.my/id/eprint/42603/
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spelling my.ums.eprints.426032025-01-14T05:00:10Z https://eprints.ums.edu.my/id/eprint/42603/ Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines Robert, Alex Walzico QP501-801 Animal biochemistry An increasing number of terpenoids that possess anticancer activity has attracted researchers' attention worldwide. This study focused on how selected terpenoids affect the cell proliferation, morphology alteration and the mechanism of cell death in breast cancer cells. The results in anti-proliferative assay showed that betulin and lupeol inhibited cell proliferation of MCF-7 with ICso 13.97±3.02 μg/ml and 24.67±1.15 μg/ml, respectively. Both compounds also inhibited MDA-MB-231 with the IC50 12.0 8±0.38 μg/ml for betulin and 17.0 0±1.09 μg/ml for lupeol. The anti-proliferation assay was also tested on normal embryonic kidney cells (293T) and the results suggested that betulin did not affect the cell proliferation in normal cell when compared to lupeol with ICso 17.17±1.04 μg/ml. Squalene did not exert any effect on all cells' proliferation. Betulin was then selected for further apoptosis and morphology investigation by DNA fragmentation, DAPI and scaning electron microscopy analysis. Betulin appeared to induce apoptosis with DNA laddering effects and apoptotic-related morphological changes when examined using DAPI and SEM. Betulin treatment on MCF-7 and MDA-MB-231 were then subjected gene expression analysis by RT-PCR with 9 genes related to apoptosis (BAX BCL,..2/ Caspase-3/ MYC and PTEN), autophagy (ATG-5 and BECN-1) and necrosis (CYLD-1 and RIPK-1). Further examination on the protein expression with apoptosis-related protein such as BAX, BCL-2, Caspase-3 and P53. Taken together, the results on gene and protein expression analysis showed that betulin demonstrated the capability in inducing cell death but not limited to apoptosis only as it might trigger other pathways that activated cell death such as autophagy and necrosis. In conclusion, further study must be conducted to understand more of the inter-relations between these cell deaths caused by betulin as this compound has the potential to be developed into a promising anticancer agent. 2020 Thesis NonPeerReviewed text en https://eprints.ums.edu.my/id/eprint/42603/1/24%20PAGES.pdf text en https://eprints.ums.edu.my/id/eprint/42603/2/FULLTEXT.pdf Robert, Alex Walzico (2020) Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines. Masters thesis, Institut Borneo Tropika dan Pemuliharaan.
institution Universiti Malaysia Sabah
building UMS Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sabah
content_source UMS Institutional Repository
url_provider http://eprints.ums.edu.my/
language English
English
topic QP501-801 Animal biochemistry
spellingShingle QP501-801 Animal biochemistry
Robert, Alex Walzico
Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines
description An increasing number of terpenoids that possess anticancer activity has attracted researchers' attention worldwide. This study focused on how selected terpenoids affect the cell proliferation, morphology alteration and the mechanism of cell death in breast cancer cells. The results in anti-proliferative assay showed that betulin and lupeol inhibited cell proliferation of MCF-7 with ICso 13.97±3.02 μg/ml and 24.67±1.15 μg/ml, respectively. Both compounds also inhibited MDA-MB-231 with the IC50 12.0 8±0.38 μg/ml for betulin and 17.0 0±1.09 μg/ml for lupeol. The anti-proliferation assay was also tested on normal embryonic kidney cells (293T) and the results suggested that betulin did not affect the cell proliferation in normal cell when compared to lupeol with ICso 17.17±1.04 μg/ml. Squalene did not exert any effect on all cells' proliferation. Betulin was then selected for further apoptosis and morphology investigation by DNA fragmentation, DAPI and scaning electron microscopy analysis. Betulin appeared to induce apoptosis with DNA laddering effects and apoptotic-related morphological changes when examined using DAPI and SEM. Betulin treatment on MCF-7 and MDA-MB-231 were then subjected gene expression analysis by RT-PCR with 9 genes related to apoptosis (BAX BCL,..2/ Caspase-3/ MYC and PTEN), autophagy (ATG-5 and BECN-1) and necrosis (CYLD-1 and RIPK-1). Further examination on the protein expression with apoptosis-related protein such as BAX, BCL-2, Caspase-3 and P53. Taken together, the results on gene and protein expression analysis showed that betulin demonstrated the capability in inducing cell death but not limited to apoptosis only as it might trigger other pathways that activated cell death such as autophagy and necrosis. In conclusion, further study must be conducted to understand more of the inter-relations between these cell deaths caused by betulin as this compound has the potential to be developed into a promising anticancer agent.
format Thesis
author Robert, Alex Walzico
author_facet Robert, Alex Walzico
author_sort Robert, Alex Walzico
title Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines
title_short Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines
title_full Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines
title_fullStr Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines
title_full_unstemmed Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines
title_sort anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines
publishDate 2020
url https://eprints.ums.edu.my/id/eprint/42603/1/24%20PAGES.pdf
https://eprints.ums.edu.my/id/eprint/42603/2/FULLTEXT.pdf
https://eprints.ums.edu.my/id/eprint/42603/
_version_ 1823092312524193792
score 13.244413

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