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

• Main Authors: Shaik M. Fakiruddin, Shaik Ahmad Kamal, Lim, Moon Nian, Nordin, Norshariza, Rosli, Rozita, Zakaria, Zubaidah, Abdullah, Syahrilnizam
• Format: Article
• Language: English
• Published: MDPI 2019
• Online Access: http://psasir.upm.edu.my/id/eprint/38282/1/38282.pdf; http://psasir.upm.edu.my/id/eprint/38282/; https://www.mdpi.com/2072-6694/11/9/1261
• Institution: Universiti Putra Malaysia

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.