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Article

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

1
UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Selangor 43400, Malaysia
2
Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam 40170, Malaysia
3
Medical Genetics Laboratory, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia
4
Genetics and Regenerative Medicine Research Centre, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Cancers 2019, 11(9), 1261; https://doi.org/10.3390/cancers11091261
Received: 21 June 2019 / Revised: 5 August 2019 / Accepted: 6 August 2019 / Published: 28 August 2019
(This article belongs to the Special Issue TRAIL Signaling in Cancer Cells)
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. View Full-Text
Keywords: mesenchymal stem cell; TRAIL; cytotherapy; apoptosis; cancer stem cells; non-small cell lung cancer mesenchymal stem cell; TRAIL; cytotherapy; apoptosis; cancer stem cells; non-small cell lung cancer
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MDPI and ACS Style

Fakiruddin, K.S.; Lim, M.N.; Nordin, N.; Rosli, R.; Zakaria, Z.; Abdullah, S. 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 2019, 11, 1261. https://doi.org/10.3390/cancers11091261

AMA Style

Fakiruddin KS, Lim MN, Nordin N, Rosli R, Zakaria Z, Abdullah S. 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. 2019; 11(9):1261. https://doi.org/10.3390/cancers11091261

Chicago/Turabian Style

Fakiruddin, Kamal Shaik, Moon N. Lim, Norshariza Nordin, Rozita Rosli, Zubaidah Zakaria, and Syahril Abdullah. 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, no. 9: 1261. https://doi.org/10.3390/cancers11091261

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