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Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans
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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) RIDSource Title Free Radical Biology and Medicine. - : Elsevier - ISSN 0891-5849
Roč. 67, FEB (2014), s. 41-50Number 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
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