PXD051376

PXD051376 is an original dataset announced via ProteomeXchange.

Title	Unlocking Selective Anticancer Mechanisms: Dinuclear Manganese Superoxide Dismutase Mimetics Combined with Pt(II) Complexes
Description	We explored the in vitro activities of the dinuclear Mn2L2Ac and Mn2L2 complexes (where HL=2-{[di(2-pyridyl)- methylamino]-methyl}phenol), possessing dual superoxide dismutase (SOD) and catalase (CAT) activity, both individually and in conjunction with various Pt(II)-complexes, either as mixtures or as the Mn2-Pt adducts. Our findings revealed a notable up to 50% enhancement in the viability of healthy human breast cells, contrasted with a viability decrease as low as 50% in breast cancer cells upon combined treatments with Mn2 SOD mimics and Pt(II) complexes. Specifically, we synthesized and characterized the self-assembled Mn2-Pt adducts (isolated Mn2L2Pt and in situ Mn2L2Pt’), linking Mn2L2-core with the carboxylate group of PtDAPCl2 (dichloro(2,3-diaminopropionic acid) platinum(II)). The SOD activity of the isolated Mn2L2Pt adduct (kSOD=1.7×107 M-1 s-1) remained intact. We elucidated key mechanisms underlying the observed biological effects. We demonstrated that Mn2-containing formulations predominantly target mitochondrial processes, differently affecting the proteome of cancerous and healthy cells. They induced downregulation of H2S signaling and expression of mitochondrial complex I and III, as well as increased oxidative phosphorylation pathways and upregulation of EGFR in cancer cells. In contrast, healthy cells showed a decrease in EGFR expression and a moderate enrichment in oxidative phosphorylation pathways.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:56:55.263.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD051376
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thibaut Vignane
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-11 16:33:57	ID requested
1	2024-08-28 08:11:10	announced
⏵ 2	2024-10-22 06:56:55	announced	2024-10-22: Updated project metadata.

10.6019/PXD051376;

10.1002/CHEM.202402685;

submitter keyword: Super-oxide dismutase mimetic,anticancer

Milos Filipovic
contact affiliation	SULFAGING group; Leibniz Institute for Analytical Sciences - ISAS - eV. Dortmund, GERMANY
contact email	milos.filipovic@isas.de
lab head
Thibaut Vignane
contact affiliation	Leibniz-Institut für Analytische Wissenschaften - ISAS - eV
contact email	thibaut.vignane@isas.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051376
     1. Label: PRIDE project
     2. Name: Unlocking Selective Anticancer Mechanisms: Dinuclear Manganese Superoxide Dismutase Mimetics Combined with Pt(II) Complexes