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Targeting of CD133+ cancer stem cells by mesenchymal stem cell expressing TRAIL reveals a prospective role of apoptotic gene regulation in non-small cell lung cancer


Citation

Shaik M. Fakiruddin, Shaik Ahmad Kamal and Lim, Moon Nian and Nordin, Norshariza and Rosli, Rozita and Zakaria, Zubaidah and Abdullah, Syahrilnizam (2019) Targeting of CD133+ cancer stem cells by mesenchymal stem cell expressing TRAIL reveals a prospective role of apoptotic gene regulation in non-small cell lung cancer. Cancers, 11 (9). art. no. 1261. pp. 1-29. ISSN 2072-6694

Abstract

Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Using assays to evaluate cell proliferation, apoptosis, and gene expression, we investigated the efficacy of MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) to target and destroy CD133+ (prominin-1 positive) NSCLC-derived CSCs. Characterization of TRAIL death receptor 5 (DR5) revealed that it was highly expressed in the CD133+ CSCs of both H460 and H2170 cell lines. The human MSC-TRAIL generated in the study maintained its multipotent characteristics, and caused significant tumor cell inhibition in NSCLC-derived CSCs in a co-culture. The MSC-TRAIL induced an increase in annexin V expression, an indicator of apoptosis in H460 and H2170 derived CD133+ CSCs. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. Using pathway-specific gene expression profiling, we uncovered candidate genes such as NFKB1, BAG3, MCL1, GADD45A, and HRK in CD133+ CSCs, which, if targeted, might increase the sensitivity of NSCLC to MSC-TRAIL-mediated inhibition. As such, our findings add credibility to the utilization of MSC-TRAIL for the treatment of NSCLC through targeting of CD133+ CSCs.


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Additional Metadata

Item Type: Article
Divisions: Faculty of Medicine and Health Science
Institute of Bioscience
DOI Number: https://doi.org/10.3390/cancers11091261
Publisher: MDPI
Keywords: Mesenchymal stem cell; TRAIL; Cytotherapy; Apoptosis; Cancer stem cells; Non-small cell lung cancer
Depositing User: Nabilah Mustapa
Date Deposited: 04 May 2020 16:11
Last Modified: 04 May 2020 16:11
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.3390/cancers11091261
URI: http://psasir.upm.edu.my/id/eprint/38282
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