PMID- 31466290
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 11
IP  - 9
DP  - 2019 Aug 28
TI  - 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.
LID - 10.3390/cancers11091261 [doi]
LID - 1261
AB  - 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.
FAU - Fakiruddin, Kamal Shaik
AU  - Fakiruddin KS
AUID- ORCID: 0000-0003-3646-3317
AD  - UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra 
      Malaysia, Selangor 43400, Malaysia. kamal@imr.gov.my.
AD  - Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), 
      National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam 
      40170, Malaysia. kamal@imr.gov.my.
FAU - Lim, Moon Nian
AU  - Lim MN
AD  - Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), 
      National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam 
      40170, Malaysia.
FAU - Nordin, Norshariza
AU  - Nordin N
AUID- ORCID: 0000-0003-1019-0496
AD  - Medical Genetics Laboratory, Department of Biomedical Sciences, Faculty of 
      Medicine & Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.
AD  - Genetics and Regenerative Medicine Research Centre, Faculty of Medicine & Health 
      Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.
FAU - Rosli, Rozita
AU  - Rosli R
AD  - UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra 
      Malaysia, Selangor 43400, Malaysia.
AD  - Medical Genetics Laboratory, Department of Biomedical Sciences, Faculty of 
      Medicine & Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.
AD  - Genetics and Regenerative Medicine Research Centre, Faculty of Medicine & Health 
      Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.
FAU - Zakaria, Zubaidah
AU  - Zakaria Z
AD  - Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), 
      National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam 
      40170, Malaysia.
FAU - Abdullah, Syahril
AU  - Abdullah S
AD  - UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra 
      Malaysia, Selangor 43400, Malaysia.
AD  - Medical Genetics Laboratory, Department of Biomedical Sciences, Faculty of 
      Medicine & Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.
AD  - Genetics and Regenerative Medicine Research Centre, Faculty of Medicine & Health 
      Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.
LA  - eng
GR  - JPP-IMR-16-038 / NMRR-16-869-30708/MINISTRY OF HEALTH (MOH) 
      MALAYSIA/International
PT  - Journal Article
DEP - 20190828
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC6770521
OTO - NOTNLM
OT  - TRAIL
OT  - apoptosis
OT  - cancer stem cells
OT  - cytotherapy
OT  - mesenchymal stem cell
OT  - non-small cell lung cancer
COIS- The authors declare no conflict of interest.
EDAT- 2019/08/31 06:00
MHDA- 2019/08/31 06:01
PMCR- 2019/08/28
CRDT- 2019/08/31 06:00
PHST- 2019/06/21 00:00 [received]
PHST- 2019/08/05 00:00 [revised]
PHST- 2019/08/06 00:00 [accepted]
PHST- 2019/08/31 06:00 [entrez]
PHST- 2019/08/31 06:00 [pubmed]
PHST- 2019/08/31 06:01 [medline]
PHST- 2019/08/28 00:00 [pmc-release]
AID - cancers11091261 [pii]
AID - cancers-11-01261 [pii]
AID - 10.3390/cancers11091261 [doi]
PST - epublish
SO  - Cancers (Basel). 2019 Aug 28;11(9):1261. doi: 10.3390/cancers11091261.