Effects of ampelopsin E towards the invasiveness of triple negative breast cancer cell line, MDA-MB-231

Breast cancer is the most common cancer and the second leading cause of cancer-related deaths in women. Its two distinctive hallmarks are rapid abnormal growth and the ability to invade and spread (metastasis). During metastasis, the cancer cells form actin-rich protrusions, called invadopodia, whic...

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Main Author: Tieng, Francis Yew Fu
Format: Thesis
Language:English
Published: 2019
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Online Access:http://psasir.upm.edu.my/id/eprint/78478/1/IB%202019%206%20ir.pdf
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spelling my-upm-ir.784782022-01-17T07:00:58Z Effects of ampelopsin E towards the invasiveness of triple negative breast cancer cell line, MDA-MB-231 2019-04 Tieng, Francis Yew Fu Breast cancer is the most common cancer and the second leading cause of cancer-related deaths in women. Its two distinctive hallmarks are rapid abnormal growth and the ability to invade and spread (metastasis). During metastasis, the cancer cells form actin-rich protrusions, called invadopodia, which degrade extracellular matrix. The current breast cancer treatment, in particular chemotherapy, comes with adverse effects like immunosuppression, development of cancer resistance and secondary tumour formation. Hence, naturally-occurring molecules claimed to be less toxic are being studied as new drug candidates. Ampelopsin E, extracted from Dryobalanops species, exhibited various pharmacological properties including anticancer and anti-inflammation. Previous study reported that ampelopsin E exhibited strong cytotoxicity against the triple negative breast cancer (TNBC) cell line, MDA-MB-231. However, there is yet any scientific evidence of the effects of ampelopsin E towards metastasis. The objective of this study was to determine the effects of ampelopsin E towards the invasiveness of TNBC cells, MDA-MB-231. To prevent ampelopsin E from causing excessive cell death, the IC20 (concentration that caused 20% inhibition of cell growth compared to the untreated group) of ampelopsin E at 24 hours (17.92 ± 2.3 μM) was determined using 3-[4,5-dimethlthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Ampelopsin E was proven to halt the rate of migration of MDA-MB-231 cells treated with ampelopsin E through scratch assay at 8, 16 and 24 hours in both untreated group and serum-starved conditions. At 24 hours, a significant (p<0.05) reduction pattern was found in the transmigration and invasion of MDA-MB-231 cells when treated with 3.75, 7.5 and 15 μM of ampelopsin E as compared to untreated group. Invadopodia and gelatin degradation assays revealed a significant (p<0.05) inhibition effect of ampelopsin E towards invadopodia formation and their gelatin degradation capability in a concentration-dependent manner in all concentrations (1.88, 3.75, 7.5 and 15 μM) when compared to untreated group. Analysis of the proteins involved in metastasis and invadopodia formation showed that ampelopsin E reduced concentration of matrix metalloproteases (MMP2, MMP9 and MMP14) and platelet-derived growth factor (PDGF) in MDA-MB-231 cells treated with ampelopsin E. In conclusion, ampelopsin E reduced the invasiveness of MDA-MB-231 cells and was proven to be a potential alternative in treating TNBC. Metastasis Breast - Cancer Cancer - Treatment 2019-04 Thesis http://psasir.upm.edu.my/id/eprint/78478/ http://psasir.upm.edu.my/id/eprint/78478/1/IB%202019%206%20ir.pdf text en public masters Universiti Putra Malaysia Metastasis Breast - Cancer Cancer - Treatment Saiful Yazan, Latifah
institution Universiti Putra Malaysia
collection PSAS Institutional Repository
language English
advisor Saiful Yazan, Latifah
topic Metastasis
Breast - Cancer
Cancer - Treatment
spellingShingle Metastasis
Breast - Cancer
Cancer - Treatment
Tieng, Francis Yew Fu
Effects of ampelopsin E towards the invasiveness of triple negative breast cancer cell line, MDA-MB-231
description Breast cancer is the most common cancer and the second leading cause of cancer-related deaths in women. Its two distinctive hallmarks are rapid abnormal growth and the ability to invade and spread (metastasis). During metastasis, the cancer cells form actin-rich protrusions, called invadopodia, which degrade extracellular matrix. The current breast cancer treatment, in particular chemotherapy, comes with adverse effects like immunosuppression, development of cancer resistance and secondary tumour formation. Hence, naturally-occurring molecules claimed to be less toxic are being studied as new drug candidates. Ampelopsin E, extracted from Dryobalanops species, exhibited various pharmacological properties including anticancer and anti-inflammation. Previous study reported that ampelopsin E exhibited strong cytotoxicity against the triple negative breast cancer (TNBC) cell line, MDA-MB-231. However, there is yet any scientific evidence of the effects of ampelopsin E towards metastasis. The objective of this study was to determine the effects of ampelopsin E towards the invasiveness of TNBC cells, MDA-MB-231. To prevent ampelopsin E from causing excessive cell death, the IC20 (concentration that caused 20% inhibition of cell growth compared to the untreated group) of ampelopsin E at 24 hours (17.92 ± 2.3 μM) was determined using 3-[4,5-dimethlthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Ampelopsin E was proven to halt the rate of migration of MDA-MB-231 cells treated with ampelopsin E through scratch assay at 8, 16 and 24 hours in both untreated group and serum-starved conditions. At 24 hours, a significant (p<0.05) reduction pattern was found in the transmigration and invasion of MDA-MB-231 cells when treated with 3.75, 7.5 and 15 μM of ampelopsin E as compared to untreated group. Invadopodia and gelatin degradation assays revealed a significant (p<0.05) inhibition effect of ampelopsin E towards invadopodia formation and their gelatin degradation capability in a concentration-dependent manner in all concentrations (1.88, 3.75, 7.5 and 15 μM) when compared to untreated group. Analysis of the proteins involved in metastasis and invadopodia formation showed that ampelopsin E reduced concentration of matrix metalloproteases (MMP2, MMP9 and MMP14) and platelet-derived growth factor (PDGF) in MDA-MB-231 cells treated with ampelopsin E. In conclusion, ampelopsin E reduced the invasiveness of MDA-MB-231 cells and was proven to be a potential alternative in treating TNBC.
format Thesis
qualification_level Master's degree
author Tieng, Francis Yew Fu
author_facet Tieng, Francis Yew Fu
author_sort Tieng, Francis Yew Fu
title Effects of ampelopsin E towards the invasiveness of triple negative breast cancer cell line, MDA-MB-231
title_short Effects of ampelopsin E towards the invasiveness of triple negative breast cancer cell line, MDA-MB-231
title_full Effects of ampelopsin E towards the invasiveness of triple negative breast cancer cell line, MDA-MB-231
title_fullStr Effects of ampelopsin E towards the invasiveness of triple negative breast cancer cell line, MDA-MB-231
title_full_unstemmed Effects of ampelopsin E towards the invasiveness of triple negative breast cancer cell line, MDA-MB-231
title_sort effects of ampelopsin e towards the invasiveness of triple negative breast cancer cell line, mda-mb-231
granting_institution Universiti Putra Malaysia
publishDate 2019
url http://psasir.upm.edu.my/id/eprint/78478/1/IB%202019%206%20ir.pdf
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