PXD028398 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Comprehensive chemical proteomics analyses reveal that the new TRi-1 and TRi-2 compounds are more specific thioredoxin reductase 1 inhibitors than Auranofin |
Description | Anticancer drugs that target cellular antioxidant systems have recently attracted much attention. Auranofin (AF) is currently evaluated in several clinical trials as an anticancer agent and targets the cytosolic and mitochondrial forms of the selenoprotein thioredoxin reductase, Txnrd1 and Txnrd2. Recently, two novel Txnrd1 inhibitors (TRi-1 and TRi-2) have been developed that showed anticancer efficacy comparable to AF, but with lower mitochondrial toxicity. However, the cellular action mechanisms of these drugs have not yet been thoroughly studied. Here we used several proteomics analyses to determine the effects of AF, TRi-1 and TRi-2 when used at IC50 concentrations with the mouse B16 melanoma and LLC lung adenocarcinoma cells, as these are often used for preclinical mouse models in evaluation of anticancer drugs. The results demonstrate that TRi-1 and TRi-2 are more specific Txnrd1 inhibitors than AF and reveal additional AF-specific effects on the cellular proteome. Interestingly, AF triggered stronger Nrf2-driven antioxidant responses than the other two compounds. Furthermore, AF affected several additional proteins, including Gsk3a, Gsk3b, Mcmbp and Eefsec, implicating additional effects on glycogen metabolism, cellular differentiation, inflammatory pathways, DNA replication and selenoprotein synthesis processes. Our proteomics data should represent a resource for researchers interested in the multidimensional analysis of proteome changes associated with oxidative stress in general, and the effects of Txnrd inhibitors and AF protein targets in particular. |
HostingRepository | PRIDE |
AnnounceDate | 2021-12-15 |
AnnouncementXML | Submission_2021-12-15_09:33:24.957.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Pierre Sabatier |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Orbitrap Fusion; LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-09-09 08:35:39 | ID requested | |
⏵ 1 | 2021-12-15 09:33:25 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Proteomics, Thioredoxin reductase, Inhibition, Cancer, Mouse |
Contact List
Roman Zubarev |
contact affiliation | Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden. Department of Pharmacological & Technological Chemistry, I.M. Sechenov First Moscow State Medical University, Moscow 119146, Russia. |
contact email | roman.zubarev@ki.se |
lab head | |
Pierre Sabatier |
contact affiliation | Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden |
contact email | pierre.sabatier@ki.se |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD028398
- Label: PRIDE project
- Name: Comprehensive chemical proteomics analyses reveal that the new TRi-1 and TRi-2 compounds are more specific thioredoxin reductase 1 inhibitors than Auranofin