Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines

Pre-clinical studies have demonstrated the efficacy of mesenchymal stem cells (MSCs) expressing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or MSC-TRAIL against several tumors. However, due to the existence of cancer stem cells (CSCs), some tumors, including non-small cell...

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Autores principales:	Kamal Shaik Fakiruddin, Moon Nian Lim, Norshariza Nordin, Rozita Rosli, Syahril Abdullah
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	non-small cell lung cancer cancer stem cell chemo-sensitization first-line chemotherapies mesenchymal stem cell TRAIL Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dd01ea0118ab45629205f86b0832e7ee
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spelling	oai:doaj.org-article:dd01ea0118ab45629205f86b0832e7ee2021-11-25T16:47:01ZChemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines10.3390/biology101111032079-7737https://doaj.org/article/dd01ea0118ab45629205f86b0832e7ee2021-10-01T00:00:00Zhttps://www.mdpi.com/2079-7737/10/11/1103https://doaj.org/toc/2079-7737Pre-clinical studies have demonstrated the efficacy of mesenchymal stem cells (MSCs) expressing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or MSC-TRAIL against several tumors. However, due to the existence of cancer stem cells (CSCs), some tumors, including non-small cell lung cancer (NSCLC), exhibit TRAIL resistance. This study was designed to evaluate the capacity of using first-line chemotherapies including cisplatin, 5-fluorouracil (5-FU) and vinorelbine to act as a chemo-sensitizer on CD133+ (prominin-1 positive) CSCs derived from NSCLC cell lines (A549, H460 and H2170) for the purpose of MSC-TRAIL-induced inhibition. We showed that MSC-TRAIL was resistant to all three chemotherapies compared to the NSCLC cell lines, suggesting that the chemotherapies had little effect on MSC-TRAIL viability. Pre-treatment using either cisplatin or 5-FU, but not with vinorelbine, was able to increase the efficacy of MSC-TRAIL to kill the TRAIL-resistant A549-derived CSCs. The study also demonstrated that both 5-FU and vinorelbine were an effective chemo-sensitizer, used to increase the anti-tumor effect of MSC-TRAIL against H460- and H2170-derived CSCs. Furthermore, pre-treatment using cisplatin was noted to enhance the effect of MSC-TRAIL in H460-derived CSCs; however, this effect was not detected in the H2170-derived CSCs. These findings suggest that a pre-treatment using certain chemotherapies in NSCLC could enhance the anti-tumor effect of MSC-TRAIL to target the CSCs, and therefore the combination of chemotherapies and MSC-TRAIL may serve as a novel approach for the treatment of NSCLC.Kamal Shaik FakiruddinMoon Nian LimNorshariza NordinRozita RosliSyahril AbdullahMDPI AGarticlenon-small cell lung cancercancer stem cellchemo-sensitizationfirst-line chemotherapiesmesenchymal stem cellTRAILBiology (General)QH301-705.5ENBiology, Vol 10, Iss 1103, p 1103 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	non-small cell lung cancer cancer stem cell chemo-sensitization first-line chemotherapies mesenchymal stem cell TRAIL Biology (General) QH301-705.5
spellingShingle	non-small cell lung cancer cancer stem cell chemo-sensitization first-line chemotherapies mesenchymal stem cell TRAIL Biology (General) QH301-705.5 Kamal Shaik Fakiruddin Moon Nian Lim Norshariza Nordin Rozita Rosli Syahril Abdullah Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines
description	Pre-clinical studies have demonstrated the efficacy of mesenchymal stem cells (MSCs) expressing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or MSC-TRAIL against several tumors. However, due to the existence of cancer stem cells (CSCs), some tumors, including non-small cell lung cancer (NSCLC), exhibit TRAIL resistance. This study was designed to evaluate the capacity of using first-line chemotherapies including cisplatin, 5-fluorouracil (5-FU) and vinorelbine to act as a chemo-sensitizer on CD133+ (prominin-1 positive) CSCs derived from NSCLC cell lines (A549, H460 and H2170) for the purpose of MSC-TRAIL-induced inhibition. We showed that MSC-TRAIL was resistant to all three chemotherapies compared to the NSCLC cell lines, suggesting that the chemotherapies had little effect on MSC-TRAIL viability. Pre-treatment using either cisplatin or 5-FU, but not with vinorelbine, was able to increase the efficacy of MSC-TRAIL to kill the TRAIL-resistant A549-derived CSCs. The study also demonstrated that both 5-FU and vinorelbine were an effective chemo-sensitizer, used to increase the anti-tumor effect of MSC-TRAIL against H460- and H2170-derived CSCs. Furthermore, pre-treatment using cisplatin was noted to enhance the effect of MSC-TRAIL in H460-derived CSCs; however, this effect was not detected in the H2170-derived CSCs. These findings suggest that a pre-treatment using certain chemotherapies in NSCLC could enhance the anti-tumor effect of MSC-TRAIL to target the CSCs, and therefore the combination of chemotherapies and MSC-TRAIL may serve as a novel approach for the treatment of NSCLC.
format	article
author	Kamal Shaik Fakiruddin Moon Nian Lim Norshariza Nordin Rozita Rosli Syahril Abdullah
author_facet	Kamal Shaik Fakiruddin Moon Nian Lim Norshariza Nordin Rozita Rosli Syahril Abdullah
author_sort	Kamal Shaik Fakiruddin
title	Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines
title_short	Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines
title_full	Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines
title_fullStr	Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines
title_full_unstemmed	Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines
title_sort	chemo-sensitization of cd133+ cancer stem cell enhances the effect of mesenchymal stem cell expressing trail in non-small cell lung cancer cell lines
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/dd01ea0118ab45629205f86b0832e7ee
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_version_	1718412987317878784

Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines

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