PMID- 32168763
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 3
DP  - 2020 Mar 11
TI  - Benefits of Combined All-Trans Retinoic Acid and Arsenic Trioxide Treatment of 
      Acute Promyelocytic Leukemia Cells and Further Enhancement by Inhibition of 
      Atypically Expressed Transglutaminase 2.
LID - 10.3390/cancers12030648 [doi]
LID - 648
AB  - Randomized trials in acute promyelocytic leukemia patients have shown that 
      treatment with a combination of all-trans retinoic acid (ATRA) and arsenic 
      trioxide (ATO) is superior in efficacy to monotherapy, with significantly 
      decreased mortality. So far, there are little data available to explain the 
      success of the ATRA and ATO combination treatment in molecular terms. We showed 
      that ATRA- and ATO-treated cells had the same capacity for superoxide production, 
      which was reduced by two-thirds in the combined treatment. Secreted inflammatory 
      biomarkers (monocyte chemoattractant protein-1 [MCP-1], interleukin-1 beta 
      [IL-1beta] and tumor necrosis factor-alpha [TNF-alpha]) were significantly decreased and 
      were further reduced in a transglutaminase 2 (TG2) expression-dependent manner. 
      The amount of secreted TNF-alpha in the supernatant of NB4 TG2 knockout cells was 
      close to 50 times lower than in ATRA-treated differentiated wild-type NB4 cells. 
      The irreversible inhibitor of TG2 NC9 not only decreased reactive oxygen species 
      production 28-fold, but decreased the concentration of MCP-1, IL-1beta and TNF-alpha 8-, 
      15- and 61-fold, respectively in the combined ATRA + ATO-treated wild-type NB4 
      cell culture. We propose that atypical expression of TG2 leads to the generation 
      of inflammation, which thereby serves as a potential target for the prevention of 
      differentiation syndrome.
FAU - Jambrovics, Karoly
AU  - Jambrovics K
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, 4032 Debrecen, Hungary.
FAU - Uray, Ivan P
AU  - Uray IP
AD  - Department of Clinical Oncology, Faculty of Medicine, University of Debrecen, 
      4032 Debrecen, Hungary.
FAU - Keillor, Jeffrey W
AU  - Keillor JW
AD  - Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, 
      ON K1N 6N5, Canada.
FAU - Fesus, Laszlo
AU  - Fesus L
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, 4032 Debrecen, Hungary.
AD  - MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy 
      of Sciences, 4032 Debrecen, Hungary.
FAU - Balajthy, Zoltan
AU  - Balajthy Z
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, 4032 Debrecen, Hungary.
LA  - eng
GR  - NKFI129139K/Nemzeti Kutatasi, Fejlesztesi es Innovacios Alap/
GR  - K129218/Nemzeti Kutatasi, Fejlesztesi es Innovacios Alap/
GR  - 05893/Natural Sciences and Engineering Research Council of Canada/
GR  - GINOP-2.3.2-15-2016-00020 | 2.3.2-15-2016-00020/MolMedEx TUMORDNS/
PT  - Journal Article
DEP - 20200311
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7139906
OTO - NOTNLM
OT  - NB4
OT  - acute promyelocytic leukemia
OT  - all-trans retinoic acid (ATRA)
OT  - arsenic trioxide (ATO), ATRA and ATO combination treatment
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/03/15 06:00
MHDA- 2020/03/15 06:01
PMCR- 2020/03/11
CRDT- 2020/03/15 06:00
PHST- 2020/02/02 00:00 [received]
PHST- 2020/03/06 00:00 [revised]
PHST- 2020/03/09 00:00 [accepted]
PHST- 2020/03/15 06:00 [entrez]
PHST- 2020/03/15 06:00 [pubmed]
PHST- 2020/03/15 06:01 [medline]
PHST- 2020/03/11 00:00 [pmc-release]
AID - cancers12030648 [pii]
AID - cancers-12-00648 [pii]
AID - 10.3390/cancers12030648 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Mar 11;12(3):648. doi: 10.3390/cancers12030648.