PXD060502

PXD060502 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of 4T1 (mouse cell line) and MDA-MB-231 (human cell line) treated with chlorpromazine hydrochloride
Description	Triple-negative breast cancer (TNBC) presents significant challenges due to its aggressive nature and high propensity for brain metastasis, often exhibiting resistance to standard treatments. In this study, we conducted a preliminary screening of potential therapeutic agents and identified chlorpromazine (CPZ) as a promising candidate for treating TNBC and its brain metastases. In vivo experiments demonstrated that CPZ robustly suppressed tumor growth and metastasis, particularly in lung and brain models, without affecting mouse body weight, indicating a favorable safety profile. Importantly, CPZ enhanced the efficacy of standard therapeutic agents such as vinorelbine and anti-PD-1 antibody. Mechanistically, CPZ induced G2/M phase arrest and triggered mitochondria-mediated intrinsic apoptosis in TNBC cells, characterized by increased ROS levels, decreased mitochondrial membrane potential, and alterations in related proteins. Furthermore, TMT-labeled quantitative proteomics analysis revealed that CPZ triggered incomplete autophagy and activated PINK1-Parkin-mediated mitophagy, marked by mitochondrial dysfunction in structure and physiological function. Inhibiting autophagy/mitophagy augmented CPZ's anticancer effects, indicating these processes may have protective roles. Overall, our study highlights the dual function of CPZ in suppressing TNBC growth and metastasis, positioning it as a promising candidate for treating this aggressive cancer. Additionally, targeting autophagy/mitophagy may serve as an effective strategy to enhance anticancer therapies against TNBC.
HostingRepository	iProX
AnnounceDate	2025-02-04
AnnouncementXML	Submission_2025-02-04_22:47:58.373.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yamin Pu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606; scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	TMT6plex reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-04 22:47:45	ID requested
⏵ 1	2025-02-04 22:47:58	announced

Dataset with its publication pending

submitter keyword: TMT;mouse,human,chlorpromazine hydrochloride,proteomics

Yong Xia
contact affiliation	Sichuan University
contact email	yxia4@scu.edu.cn
lab head
Yamin Pu
contact affiliation	Sichuan University
contact email	1935252292@qq.com
dataset submitter

iProX dataset URI