Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans

Stapelberg, M.; Zobalová, Renata; Nguyen, M.N.; Walker, T.; Stantic, M.; Goodwin, J.; Pasdar, E.A.; Thai, T.; Prokopová, Kateřina; Yan, B.; Hall, S.; de Pennington, N.; Thomas, S.R.; Grant, G.; Štursa, Jan; Bajziková, Martina; Meedeniya, A.C.B.; Truksa, Jaroslav; Ralph, S. J.; Ansorge, O.; Dong, L.-F.; Neužil, Jiří

doi:https://dx.doi.org/10.1016/j.freeradbiomed.2013.10.003

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Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans

1.

SYSNO ASEP	0431273
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans
Author(s)	Stapelberg, M. (AU) Zobalová, Renata (BTO-N)_RID Nguyen, M.N. (AU) Walker, T. (AU) Stantic, M. (AU) Goodwin, J. (AU) Pasdar, E.A. (AU) Thai, T. (AU) Prokopová, Kateřina (BTO-N)_ORCID Yan, B. (AU) Hall, S. (GB) de Pennington, N. (GB) Thomas, S.R. (AU) Grant, G. (AU) Štursa, Jan (UOCHB-X) Bajziková, Martina (BTO-N)_RID Meedeniya, A.C.B. (AU) Truksa, Jaroslav (BTO-N)_{RID, ORCID} Ralph, S. J. (AU) Ansorge, O. (GB) Dong, L.-F. (AU) Neužil, Jiří (BTO-N)_RID
Source Title	Free Radical Biology and Medicine. - : Elsevier - ISSN 0891-5849 Roč. 67, FEB (2014), s. 41-50
Number of pages	10 s.
Language	eng - English
Country	US - United States
Keywords	IDO ; Tumor-initiating cells ; Mitocans ; Mitochondrially targeted vitamin E succinate
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	GAP301/10/1937 GA ČR - Czech Science Foundation (CSF)
	GAP305/12/1708 GA ČR - Czech Science Foundation (CSF)
Institutional support	BTO-N - RVO:86652036 ; UOCHB-X - RVO:61388963
UT WOS	000331854200005
DOI	10.1016/j.freeradbiomed.2013.10.003
Annotation	Tumor-initiating cells (TICs) often survive therapy and give rise to second-line tumors. We tested the plausibility of sphere cultures as models of TICs. Microarray data and microRNA data analysis confirmed the validity of spheres as models of TICs for breast and prostate cancer as well as mesothelioma cell lines. Microarray data analysis revealed the Trp pathway as the only pathway upregulated significantly in all types of studied TICs, with increased levels of indoleamine-2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme of Trp metabolism along the kynurenine pathway. All types of TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. IDO1 expression was regulated via both transcriptional and posttranscriptional mechanisms, depending on the cancer type. Serial transplantation of TICs in mice resulted in gradually increased IDO1. Mitocans, represented by et-tocopheryl succinate and mitochondrially targeted vitamin E succinate (MitoVES), suppressed IDO1 in TICs. MitoVES suppressed IDO1 in TICs with functional mitochondrial complex II, involving transcriptional and posttranscriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work indicates that IDO1 is increased in TICs and that mitocans suppress the protein. (C) 2013 Elsevier Inc. All rights reserved.
Workplace	Institute of Biotechnology
Contact	Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
Year of Publishing	2015

Number of the records: 1