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

    Author(s)
    Stapelberg, Michael
    Zobalova, Renata
    Nguyen, Maria Nga
    Walker, Tom
    Stantic, Marina
    Goodwin, Jacob
    Pasdar, Elham Alizadeh
    Thai, Thuan
    Prokopova, Katerina
    Yan, Bing
    Hall, Susan
    de Pennington, Nicholas
    Thomas, Shane R
    Grant, Gary
    Stursa, Jan
    Bajzikova, Martina
    Meedeniya, Adrian CB
    Truksa, Jaroslav
    Ralph, Stephen J
    Ansorge, Olaf
    Dong, Lan-Feng
    Neuzil, Jiri
    Griffith University Author(s)
    Neuzil, Jiri
    Stapelberg, Michael
    Zobalova, Renata
    Nguyen, Maria T.
    Hall, Susan
    Stantic, Marina
    Ralph, Stephen J.
    Grant, Gary D.
    Dong, Lan-feng
    Meedeniya, Adrian C.
    Goodwin, Jacob
    Alizadeh Pasdar, Elham
    Stursa, Jan
    Walker, Tom
    Yan, Bing
    Year published
    2014
    Metadata
    Show full item record
    Abstract
    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 ...
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    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 a-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.
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    Journal Title
    Free Radical Biology and Medicine
    Volume
    67
    DOI
    https://doi.org/10.1016/j.freeradbiomed.2013.10.003
    Subject
    Medical and Health Sciences not elsewhere classified
    Medicinal and Biomolecular Chemistry
    Biochemistry and Cell Biology
    Medical Biochemistry and Metabolomics
    Publication URI
    http://hdl.handle.net/10072/65062
    Collection
    • Journal articles

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