PMID- 34282169
OWN - NLM
STAT- MEDLINE
DCOM- 20211130
LR  - 20211130
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Jul 19
TI  - Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor 
      effect of IL-1beta-stimulated human umbilical cord mesenchymal stem cells.
PG  - 14720
LID - 10.1038/s41598-021-94006-w [doi]
LID - 14720
AB  - Breast cancer is the leading cause of cancer-related death for women. In breast 
      cancer treatment, targeted therapy would be more effective and less harmful than 
      radiotherapy or systemic chemotherapy. Tumor necrosis factor-related 
      apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in cancer 
      cells but not in normal cells. Mesenchymal stem cells have shown great 
      therapeutic potential in cancer therapy owing to their ability of homing to tumor 
      sites and secreting many kinds of anti-tumor proteins including TRAIL. In this 
      study, we found that IL-1beta-stimulated human umbilical cord-derived mesenchymal 
      stem cells (hUCMSCs) enhance the expression of membrane-bound and soluble TRAIL. 
      Cellular FADD-like IL-1beta-converting enzyme inhibitory protein (cFLIP) is an 
      important regulator in TRAIL-mediated apoptosis and relates to TRAIL resistance 
      in cancer cells. Previous studies have shown that embelin, which is extracted 
      from Embelia ribes, can increase the TRAIL sensitivity of cancer cells by 
      reducing cFLIP expression. Here we have demonstrated that cFLIP(L) is correlated 
      with TRAIL-resistance and that embelin effectively downregulates cFLIP(L) in 
      breast cancer cells. Moreover, co-culture of IL-1beta-stimulated hUCMSCs with 
      embelin-treated breast cancer cells could effectively induce apoptosis in breast 
      cancer cells. The combined effects of embelin and IL-1beta-stimulated hUCMSCs may 
      provide a new therapeutic strategy for breast cancer therapy.
CI  - (c) 2021. The Author(s).
FAU - Liang, Ya-Han
AU  - Liang YH
AD  - Department of Anatomy, Institute of Anatomy and Cell Biology, School of Medicine, 
      National Yang Ming Chiao Tung University, Peitou, Taipei, 112, Taiwan, ROC.
FAU - Wu, Jiann-Ming
AU  - Wu JM
AD  - General Surgery Division, Far Eastern Memorial Hospital, New Taipei City, Taiwan, 
      ROC.
FAU - Teng, Jui-Wen
AU  - Teng JW
AD  - Department of Anatomy, Institute of Anatomy and Cell Biology, School of Medicine, 
      National Yang Ming Chiao Tung University, Peitou, Taipei, 112, Taiwan, ROC.
FAU - Hung, Eric
AU  - Hung E
AD  - Department of Anatomy, Institute of Anatomy and Cell Biology, School of Medicine, 
      National Yang Ming Chiao Tung University, Peitou, Taipei, 112, Taiwan, ROC.
FAU - Wang, Hwai-Shi
AU  - Wang HS
AD  - Department of Anatomy, Institute of Anatomy and Cell Biology, School of Medicine, 
      National Yang Ming Chiao Tung University, Peitou, Taipei, 112, Taiwan, ROC. 
      hswang@ym.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210719
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Benzoquinones)
RN  - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein)
RN  - 0 (IL1B protein, human)
RN  - 0 (Interleukin-1beta)
RN  - SHC6U8F5ER (embelin)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Benzoquinones/*pharmacology
MH  - Breast Neoplasms/metabolism/*pathology/therapy
MH  - CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Down-Regulation/drug effects
MH  - Drug Screening Assays, Antitumor
MH  - Drug Synergism
MH  - Female
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - MCF-7 Cells
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/drug effects/*physiology
MH  - Umbilical Cord/cytology/drug effects
PMC - PMC8289868
COIS- The authors declare no competing interests.
EDAT- 2021/07/21 06:00
MHDA- 2021/12/01 06:00
PMCR- 2021/07/19
CRDT- 2021/07/20 06:24
PHST- 2021/02/01 00:00 [received]
PHST- 2021/07/05 00:00 [accepted]
PHST- 2021/07/20 06:24 [entrez]
PHST- 2021/07/21 06:00 [pubmed]
PHST- 2021/12/01 06:00 [medline]
PHST- 2021/07/19 00:00 [pmc-release]
AID - 10.1038/s41598-021-94006-w [pii]
AID - 94006 [pii]
AID - 10.1038/s41598-021-94006-w [doi]
PST - epublish
SO  - Sci Rep. 2021 Jul 19;11(1):14720. doi: 10.1038/s41598-021-94006-w.