-
Tytuł:
-
Disulfiram potentiates the anticancer effect of cisplatin in atypical teratoid/rhabdoid tumors (AT/RT).
-
Autorzy:
-
Jangra A; Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, South Korea; Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Choi SA; Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, South Korea; Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Yang J; Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, South Korea; Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Koh EJ; Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, South Korea; Regional Emergency Medical Center, Seoul National University Hospital, Seoul, South Korea.
Phi JH; Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, South Korea; Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Lee JY; Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, South Korea; Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea; Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea.
Wang KC; Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, South Korea; Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Kim SK; Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, South Korea; Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: .
-
Źródło:
-
Cancer letters [Cancer Lett] 2020 Aug 28; Vol. 486, pp. 38-45. Date of Electronic Publication: 2020 May 16.
-
Typ publikacji:
-
Journal Article; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Publication: Limerick : Elsevier Science Ireland
Original Publication: Amsterdam, Elsevier/North-Holland.
-
MeSH Terms:
-
Brain Neoplasms/*drug therapy
Cisplatin/*pharmacology
Disulfiram/*pharmacology
Rhabdoid Tumor/*drug therapy
Teratoma/*drug therapy
Activating Transcription Factor 3/physiology ; Aldehyde Dehydrogenase/metabolism ; Animals ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Cisplatin/administration & dosage ; Disulfiram/administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Rhabdoid Tumor/pathology ; Teratoma/pathology
-
Contributed Indexing:
-
Keywords: ALDH; AT/RT; ATF3; Cisplatin; Combination therapy; Disulfiram
-
Substance Nomenclature:
-
0 (ATF3 protein, human)
0 (Activating Transcription Factor 3)
EC 1.2.1.3 (Aldehyde Dehydrogenase)
Q20Q21Q62J (Cisplatin)
TR3MLJ1UAI (Disulfiram)
-
SCR Disease Name:
-
Typical Teratoid Rhabdoid Tumor
-
Entry Date(s):
-
Date Created: 20200520 Date Completed: 20210127 Latest Revision: 20210127
-
Update Code:
-
20240105
-
DOI:
-
10.1016/j.canlet.2020.05.006
-
PMID:
-
32428661
-
Atypical teratoid/rhabdoid tumor (AT/RT) is the most malignant tumor of the central nervous system that generally occurs in young children. Despite the use of intensive multimodal therapy for AT/RT, the prognosis is still poor. The brain tumor initiating cells in AT/RT cells has been suggested as one of the challenges in AT/RT treatment. These cells have high expression of aldehyde dehydrogenase (ALDH). We investigated the combination effect of the ALDH inhibitor, disulfiram and cisplatin in the treatment of AT/RT cells. Isobologram analysis revealed that the combination therapy synergistically increases AT/RT cell death. The enzyme activity of ALDH AT/RT cells was effectively reduced by the combination therapy. We proposed that the synergistic augmentation occurs, at least partially through an increase in cleaved Poly (ADP-ribose) polymerase (PARP)-dependent apoptosis mediated by activating transcription factor 3 (ATF3). In the AT/RT mouse model, the combination therapy decreased tumor volume and prolonged survival. Immunofluorescence assay in mouse brain tissues were consistent with the expression of ATF3 and cleaved PARP. Our study demonstrates enhanced anti-cancer effect of combination therapy of disulfiram and cisplatin. This combination might provide a viable therapeutic strategy for AT/RT patients.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest in regard to this study.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
