PXD064464

PXD064464 is an original dataset announced via ProteomeXchange.

Title	Mechanistic Insights into the Antitumor Activity of Cu²⁺-based Complexes: Targeting Apoptosis and Cellular Pathways in MCF-7 Breast Cancer Cells
Description	Cancer’s global burden highlights the urgent need for more effective therapies. Metalbased drugs, particularly copper complexes, offer promising alternatives due to copper’s diverse biological functions. This study investigates the antitumor potential of two novel dinuclear Cu²⁺ complexes, [Cu2(µ-CH3COO)(L)(OH2)]·2H2O (R9) and [Cu2(µ-OH)(HL)(OH2)]ClO4·2H2O (R10), in MCF-7 breast cancer cells. Both compounds exhibited greater cytotoxicity than cisplatin, with IC₅₀ values of 1.01 ± 0.09 μM (R9) and 1.27 ± 0.14 μM (R10), while showing selectivity toward cancer cells, as indicated by higher IC₅₀ values in healthy MCF10A cells. Treated MCF-7 cells showed increased granularity, mitochondrial membrane depolarization, and elevated reactive oxygen species. At IC₅₀ concentrations, cell cycle analysis revealed Sub-G1 accumulation and DNA fragmentation (TUNEL assay), indicating apoptosis via intrinsic pathways, supported by caspase 9 activation. Label-free proteomics revealed distinct mechanisms for R10 compared to cisplatin. In R10-treated cells, key downregulated pathways included actin cytoskeleton regulation, viral carcinogenesis, and PI3K-Akt signaling; upregulated pathways involved ribosome biogenesis, necroptosis, and metabolism. Apoptosis-related proteins such as lamin B1, NRAS, and MAPKs were downregulated, while AIFM1 was upregulated. These findings support the potential of dinuclear Cu²⁺ complexes as effective antitumor agents with mechanisms distinct from cisplatin, possibly offering superior efficacy through apoptosis induction.
HostingRepository	PRIDE
AnnounceDate	2025-11-24
AnnouncementXML	Submission_2025-11-23_17:48:53.372.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Proteomics Unit
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-30 17:52:25	ID requested
⏵ 1	2025-11-23 17:48:56	announced

Ghasemishahrestani Z, de Oliveira SSC, Dos Santos Moraes Francisco R, Ramos LFC, Dos Santos RM, Domont GB, Rey NA, Dos Santos ALS, Nogueira FCS, Pereira MD, -complexes disrupt cellular pathways and rewire the breast cancer proteome. J Proteomics, 323():105570(2026) [pubmed]

10.1016/j.jprot.2025.105570;

submitter keyword: Cu2+ complexes

Reactive oxygen species

Apoptosis

Anticancer activity

Cytotoxicity

Proteomics

Fábio César Sousa Nogueira
contact affiliation	Proteomics Unit, Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-909 Rio de Janeiro, RJ, Brazil; Laboratory of Proteomics, LADETEC, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-598 Rio de Janeiro, RJ, Brazi
contact email	fabiocsn@gmail.com
lab head
Proteomics Unit
contact affiliation	UFRJ
contact email	unidadeproteomica@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD064464

PRIDE project URI

• PRIDE
  1. PXD064464
     1. Label: PRIDE project
     2. Name: Mechanistic Insights into the Antitumor Activity of Cu²⁺-based Complexes: Targeting Apoptosis and Cellular Pathways in MCF-7 Breast Cancer Cells