Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells

The Triple Negative Breast Cancer (TNBC) is the most invasive breast cancer subtype enriched with cancer stem cells (CSCs). The absence of estrogen, progesterone and HER2 receptors make TNBCs difficult to be targeted by existing chemotherapy treatments. This study aimed to identify the effects of ci...

Full description

Saved in:

Bibliographic Details
Main Author:	Abu Bakar, Nur Fitriyani Afiqah
Format:	Thesis
Language:	English
Published:	2021
Subjects:	QD Chemistry
Online Access:	http://eprints.utm.my/id/eprint/102143/1/NurFitriyaniAfiqahMFS2021.pdf.pdf
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my-utm-ep.102143
record_format	uketd_dc
spelling	my-utm-ep.1021432023-08-07T08:09:40Z Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells 2021 Abu Bakar, Nur Fitriyani Afiqah QD Chemistry The Triple Negative Breast Cancer (TNBC) is the most invasive breast cancer subtype enriched with cancer stem cells (CSCs). The absence of estrogen, progesterone and HER2 receptors make TNBCs difficult to be targeted by existing chemotherapy treatments. This study aimed to identify the effects of cisplatin and C. nutans as combined treatment on MDA-MB-231 and MDA-MB-468 breast cancer cells representing the Triple Negative Breast Cancer subtype. The effect of cisplatin, C. nutans and their combination were investigated on the viability and proliferative ability of MDA-MB-231 and MDA-MB-468 cells using Cell Titer-Glo® 2.0 and CyQuant NF Proliferation Assays, respectively. Three different treatments were studied, Cisplatin at 0-15.23 µg/mL, C. nutans at 0-50 µg/mL and combined treatment of 3.05 µg/mL cisplatin with C. nutans at 0-50 µg/mL. Next, a drug interaction study was done using isobologram-combination index analysis. The effect of these treatments to induce apoptosis in both cancer cells was also determined using Caspase-Glo® 3/7. Additionally, cell invasion inhibition of MDA-MB-231 breast cancer cells was examined using Cultrex BME Cell Invasion assays. The expression of cancer stem cells protein (CD49f) and differentiation marker (CK18) was also elucidated using flow cytometry analysis. The results showed that the combined cisplatin-C. nutans treatment exhibited potent and synergistic anticancer effects on MDA-MB-231 and MDA-MB-468 breast cancer cells. Cisplatin and C. nutans alone reduced MDA-MB-231 cell viability and proliferation in a dose-dependent manner by 6-69% and 1-59% respectively, whereas 13-78% when in combination. Greater cell viability and proliferation inhibition was seen in MDA-MB-468 by cisplatin (11-75%) or C. nutans (2-73%) alone or as combined treatment (15-77%). Significant apoptotic induction were exhibited in MDA-MB-231 (2.73%) and MDA-MB-468 cells (3.53%) upon combined treatment in comparison to a negligible apoptotic induction exerted by cisplatin or C. nutans alone. Furthermore, the MDA-MB-231 cell invasion ability was significantly reduced to 36% upon combined treatment compared to cisplatin (51%) and C. nutans (58%) alone. At protein level, cisplatin and C. nutans differentially regulated protein markers associated with cancer stem cells (CD49f) and differentiation (CK18). The expression of CK18 upon cisplatin, C. nutans and combined treatments were up-regulated whereas the expression of CD49f was down-regulated upon cisplatin and combined cisplatin-C. nutans treatments. Interestingly, C. nutans alone caused a negligible change to CD49f expression. Altogether, these findings suggest that cisplatin-C. nutans combination is a potent anticancer agent for a targeted therapy against MDA-MB-231 cells and other CSCs-enriched cancers. The up-regulation of CK18 correlates with the induction of CSCs differentiation, on the other hand, down-regulation of CD49f links to cancer stem cells inhibition. The ability of C. nutans in sensitizing breast cancer cells against cisplatin was highlighted as a promising strategy to enhance anticancer effect of cisplatin and thus for the treatment and management of TNBC as a whole. 2021 Thesis http://eprints.utm.my/id/eprint/102143/ http://eprints.utm.my/id/eprint/102143/1/NurFitriyaniAfiqahMFS2021.pdf.pdf application/pdf en public http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:146350 masters Universiti Teknologi Malaysia Faculty of Science
institution	Universiti Teknologi Malaysia
collection	UTM Institutional Repository
language	English
topic	QD Chemistry
spellingShingle	QD Chemistry Abu Bakar, Nur Fitriyani Afiqah Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells
description	The Triple Negative Breast Cancer (TNBC) is the most invasive breast cancer subtype enriched with cancer stem cells (CSCs). The absence of estrogen, progesterone and HER2 receptors make TNBCs difficult to be targeted by existing chemotherapy treatments. This study aimed to identify the effects of cisplatin and C. nutans as combined treatment on MDA-MB-231 and MDA-MB-468 breast cancer cells representing the Triple Negative Breast Cancer subtype. The effect of cisplatin, C. nutans and their combination were investigated on the viability and proliferative ability of MDA-MB-231 and MDA-MB-468 cells using Cell Titer-Glo® 2.0 and CyQuant NF Proliferation Assays, respectively. Three different treatments were studied, Cisplatin at 0-15.23 µg/mL, C. nutans at 0-50 µg/mL and combined treatment of 3.05 µg/mL cisplatin with C. nutans at 0-50 µg/mL. Next, a drug interaction study was done using isobologram-combination index analysis. The effect of these treatments to induce apoptosis in both cancer cells was also determined using Caspase-Glo® 3/7. Additionally, cell invasion inhibition of MDA-MB-231 breast cancer cells was examined using Cultrex BME Cell Invasion assays. The expression of cancer stem cells protein (CD49f) and differentiation marker (CK18) was also elucidated using flow cytometry analysis. The results showed that the combined cisplatin-C. nutans treatment exhibited potent and synergistic anticancer effects on MDA-MB-231 and MDA-MB-468 breast cancer cells. Cisplatin and C. nutans alone reduced MDA-MB-231 cell viability and proliferation in a dose-dependent manner by 6-69% and 1-59% respectively, whereas 13-78% when in combination. Greater cell viability and proliferation inhibition was seen in MDA-MB-468 by cisplatin (11-75%) or C. nutans (2-73%) alone or as combined treatment (15-77%). Significant apoptotic induction were exhibited in MDA-MB-231 (2.73%) and MDA-MB-468 cells (3.53%) upon combined treatment in comparison to a negligible apoptotic induction exerted by cisplatin or C. nutans alone. Furthermore, the MDA-MB-231 cell invasion ability was significantly reduced to 36% upon combined treatment compared to cisplatin (51%) and C. nutans (58%) alone. At protein level, cisplatin and C. nutans differentially regulated protein markers associated with cancer stem cells (CD49f) and differentiation (CK18). The expression of CK18 upon cisplatin, C. nutans and combined treatments were up-regulated whereas the expression of CD49f was down-regulated upon cisplatin and combined cisplatin-C. nutans treatments. Interestingly, C. nutans alone caused a negligible change to CD49f expression. Altogether, these findings suggest that cisplatin-C. nutans combination is a potent anticancer agent for a targeted therapy against MDA-MB-231 cells and other CSCs-enriched cancers. The up-regulation of CK18 correlates with the induction of CSCs differentiation, on the other hand, down-regulation of CD49f links to cancer stem cells inhibition. The ability of C. nutans in sensitizing breast cancer cells against cisplatin was highlighted as a promising strategy to enhance anticancer effect of cisplatin and thus for the treatment and management of TNBC as a whole.
format	Thesis
qualification_level	Master's degree
author	Abu Bakar, Nur Fitriyani Afiqah
author_facet	Abu Bakar, Nur Fitriyani Afiqah
author_sort	Abu Bakar, Nur Fitriyani Afiqah
title	Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells
title_short	Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells
title_full	Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells
title_fullStr	Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells
title_full_unstemmed	Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells
title_sort	cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and mda-mb-468 triple negative breast cancer cells
granting_institution	Universiti Teknologi Malaysia
granting_department	Faculty of Science
publishDate	2021
url	http://eprints.utm.my/id/eprint/102143/1/NurFitriyaniAfiqahMFS2021.pdf.pdf
_version_	1776100856064638976

Cytotoxic effects of combined cisplatin and clinacanthus nutans in mda-mb-231 and MDA-MB-468 triple negative breast cancer cells

Similar Items