Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24145120
DOI
10.1016/j.freeradbiomed.2013.10.003
PII: S0891-5849(13)00634-5
Knihovny.cz E-resources
- Keywords
- Free radicals, IDO, Mitocans, Mitochondrially targeted vitamin E succinate, Tumor-initiating cells,
- MeSH
- alpha-Tocopherol pharmacology MeSH
- Fusion Regulatory Protein-1 genetics metabolism MeSH
- Antineoplastic Agents, Phytogenic pharmacology MeSH
- Indoleamine-Pyrrole 2,3,-Dioxygenase genetics metabolism MeSH
- Kynurenine metabolism MeSH
- Humans MeSH
- Metabolic Networks and Pathways drug effects genetics MeSH
- Mitochondria drug effects metabolism MeSH
- Cell Line, Tumor MeSH
- Neoplastic Stem Cells drug effects metabolism pathology MeSH
- Large Neutral Amino Acid-Transporter 1 genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Electron Transport Complex II genetics metabolism MeSH
- Signal Transduction MeSH
- Tryptophan metabolism MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Fusion Regulatory Protein-1 MeSH
- Antineoplastic Agents, Phytogenic MeSH
- IDO1 protein, human MeSH Browser
- Indoleamine-Pyrrole 2,3,-Dioxygenase MeSH
- Kynurenine MeSH
- Large Neutral Amino Acid-Transporter 1 MeSH
- Electron Transport Complex II MeSH
- Tryptophan MeSH
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 α-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.
Department of Neurosurgery John Radcliffe Hospital Oxford OX3 9DU UK
Institute of Biotechnology Academy of Sciences of the Czech Republic Prague 142 20 Czech Republic
School of Medical Science Griffith Health Institute Griffith University Southport 4222 QLD Australia
School of Pharmacy Griffith Health Institute Griffith University Southport 4222 QLD Australia
References provided by Crossref.org
Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents
