PXD028398-1

PXD028398 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:35:39	ID requested
⏵ 1	2021-12-15 09:33:25	announced

Dataset with its publication pending

submitter keyword: Proteomics, Thioredoxin reductase, Inhibition, Cancer, Mouse

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

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PRIDE project URI

• PRIDE
  1. PXD028398
     1. Label: PRIDE project
     2. Name: Comprehensive chemical proteomics analyses reveal that the new TRi-1 and TRi-2 compounds are more specific thioredoxin reductase 1 inhibitors than Auranofin