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Mitoxantrone impacts on proteoform abundance in HR proficient and deficient ovarian cancer cells

ABSTRACT: Mitoxantrone (MX) is regularly used to treat several cancers, yet despite its long history in the clinic, recent studies continue to unveil novel protein targets that may contribute to the cytotoxic effects of the drug, as well as potential non-canonical antitumor activity. A better understanding of MX’s cellular targets is required to fully comprehend the molecular consequences of treatment and to interpret MX-sensitivity in homologous recombination (HR)-deficient cancer. The mass spectrometry samples reported here represent the analysis of MX impacts on proteoform abundance in HR-deficient or proficient UWB1.289 ovarian cancer cells using TMT-labeled quantitative proteomics.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Nicholas Woods

LAB HEAD: Nicholas Woods

PROVIDER: PXD069401 | Pride | 2025-12-01

REPOSITORIES: Pride

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			Action	DRS
	20250214_SW_F.msf	Msf
	20250214_SW_F1.raw	Raw
	20250214_SW_F10.raw	Raw
	20250214_SW_F11.raw	Raw
	20250214_SW_F12.raw	Raw

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Publications

Surveying the Proteome-Wide Landscape of Mitoxantrone and Examining Drug Sensitivity in BRCA1-Deficient Ovarian Cancer Using Quantitative Proteomics.

Wallin Savanna S Pandithar Sneha S Singh Sarbjit S Kumar Siddhartha S Natarajan Amarnath A Borgstahl Gloria E O GEO Woods Nicholas N

Proteomes 20251114 4

<b>Background</b>: Mitoxantrone (MX) is regularly used to treat several cancers. Despite its long history in the clinic, recent studies continue to unveil novel protein targets. These targets may contribute to the cytotoxic effects of the drug, as well as potential non-canonical antitumor activity. A better understanding of MX's cellular targets is required to fully comprehend the molecular consequences of treatment and to interpret MX sensitivity in homologous recombination (HR)-deficient cance ...[more]

PMID: 41283651

Similar Datasets

Surveying the proteome-wide landscape of Mitoxantrone and examining drug-sensitivity in BRCA1-deficient ovarian cancer using quantitative proteomics

Project description:Mitoxantrone (MX) is regularly used to treat several cancers, yet despite its long history in the clinic, recent studies continue to unveil novel protein targets that may contribute to the cytotoxic effects of the drug, as well as potential non-canonical antitumor activity. A better understanding of MX’s cellular targets is required to fully comprehend the molecular consequences of treatment and to interpret MX-sensitivity in homologous recombination (HR)-deficient cancer. Here, we describe two approaches used to evaluate MX-activity in HR-deficient UWB1.289 ovarian cancer cells and survey the binding profile of MX using TMT-labeled quantitative proteomics and chemoproteomics. Mass spectrometry (MS) analysis of cellular extracts from MX-treated BRCA1- UWB1.289 cells revealed a unique downregulation of pathways instrumental to maintaining genomic stability, including single-strand annealing. Moreover, the BRCA1- cells exhibited a significant upregulation of proteins involved in ribosome biogenesis and RNA processing. Additional MS analyses following affinity-purification using a biotinylated-mitoxantrone probe (MXP) corrobo-rated these findings, which showed considerable targeting of proteins involved in ge-nomic maintenance and RNA processing. Our results suggest that an interplay of both canonical and non-canonical MX-antitumor activity overwhelms the BRCA1- cells. Fur-thermore, this study aids in characterizing the target landscape of MX, ultimately providing insights into off-target effects and MX-action in HR-deficient cancer.

2025-12-01 | PXD069034 | Pride

Proteomic profiling of HT1080 fibrosarcoma cells of mesenchymal or amoeboid migratory phenotype

Project description:Amoeboid and mesenchymal migration of cancer cells both contribute to metastatic spreading of tumors. To characterize proteome changes underlying the different migratory modes, we performed mass spectrometry profiling of HT1080 fibrosarcoma cells undergoing mesenchymal-amoeboid transition induced by either doxycycline-inducible constitutively active RhoA or dasatinib treatment. Cells were kept in three-dimensional collagen gels with or without induction for 48 hours, lysed and processed for mass spectrometry analysis. In case of the inducible RhoA system, we also performed parallel two-dimensional experiments with cells on top of a dense layer of collagen (it was not feasible with dasatinib treatment).

2020-04-23 | PXD010425 | Pride

affy_cotton_2011_12 - Comparative transcriptional profiling of cotton fibers in Gossypium hirsutum and Gossypium barbadense using EST pyrosequencing and microarray hybridization

Project description:affy_cotton_2011_12 - affy_cotton_2011_12 - In this study we characterized the fiber transcriptomes of the two species, Gossypium hirsutum and Gossypium barbadense that were parental genotypes of a RIL mapping population used previously for phenotypic QTL and expression QTL mapping., We used 454 deep pyrosequencing to characterize cDNAs from developing fibers at two key developmental time-points; 10 and 22 days post anthesis. A unigene set was assembled and annotated, and differential digital gene expression was assessed from the different time-point and genotype representations of the reads within assembled contigs. As a complementary approach, we conducted microarray-based hybridization profiling using the cotton Affymetrix gene chip and labeled cDNAs from fibers at 11 dpa and for the same two genotypes and compared differentially expressed genes identified by the two platforms. The 454 unigenes were also mined for the presence of microsatellite repeats and SNPs that will be useful markers for mapping and marker-assisted selection in cotton improvement.-Total RNA was extracted from 11 dpa-old fibers from the two genotypes, Guazuncho 2 (Gossypium hirsutum) and VH8-4602 (G. barbadense), and included two replicates of each. RNA was checked for quality and quantity using an Agilent Bioanalyser 2100 (Agilent Technologies, Santa Clara, CA, USA, http://www.home.agilent.com) following the manufacturer’s recommendations. The RNA was sent to the Australian Genome Research Facility Ltd. (http://www.agrf.org.au, Melbourne, Victoria, Australia) for labeling and hybridization to the Affymetrix Genechip® Cotton Genome Array (21,854 genes) (Affymetrix, http://www.affymetrix.com/). - 4 arrays - Cotton; x comparison between two genotypes in cell type This represents the gene expression component of the study only

2012-10-03 | E-GEOD-36876 | biostudies-arrayexpress

affy_cotton_2011_12-Comparative transcriptional profiling of cotton fibers in Gossypium hirsutum and Gossypium barbadense using EST pyrosequencing and microarray hybridization

2013-07-01 | E-GEOD-43528 | biostudies-arrayexpress

Characterization of the redox proteome of Drosophila melanogaster S2 cells and w1118 fly eyes.

Project description:Reactive oxygen species (ROS) serve as intracellular signaling molecules; however, in excess ROS molecules are damaging to biomacromolecules such as DNA, lipids, and proteins. The excess accumulation of ROS leads to oxidative stress, disrupting redox homeostasis in the cell and has been linked with aging and neurodegenerative disease. The eye is particularly vulnerable to oxidative stress due to the tissue’s high energy demand and generation of ROS by products. In proteins, the thiol group on cysteine residues is susceptible to oxidation. Cysteine residues have multiple oxidation states that can be classified into two categories—reversible and irreversible. Irreversible oxidation states include sulfinic and sulfonic acids, which may alter or impair the activity of the protein depending on the position of the cysteine residue. In contrast, reversible oxidation states include sulfenic acid or inter- and intramolecular disulfides, and can often function as redox sensors in the cell. Here, we sought to evaluate how increasing amounts of oxidative stress alters the redox proteome landscape in Drosophila. To characterize the redox proteome, we developed an iodoTMT-multiplex isolation, labeling, and enrichment method to identify cysteine availability and potential oxidation in both S2 cells and w1118 fly eyes. To do this, we exposed S2 cells to 20mM H2O2 relative to control (untreated), and w1118 flies to prolonged blue light versus an untreated control, followed by redox proteome profiling with iodoTMT-sixplex reagents.

2023-04-27 | PXD034050 | Pride

Characterization of the redox proteome in Drosophila melanogaster aging eyes.

Project description:During oxidative stress, reactive oxygen species (ROS) can modify and damage cellular proteins. In particular, the thiol groups of cysteine residues can undergo reversible or irreversible oxidative post-translation modifications (PTMs). Identifying the redox-sensitive cysteines on a proteome-wide scale can provide insight into those proteins that act as redox sensors or become irreversibly damaged upon exposure to high levels of ROS. Aging is accompanied by oxidative stress, and oxygen-rich tissues such as the eye are particularly vulnerable because of its high energy demand and generation of ROS byproducts, which increases the risk for ocular disease. In this study, we profiled the redox proteome of the aging Drosophila eye to identify cysteine residues that are modified by age-associated ROS.

2023-04-27 | PXD036110 | Pride

Transcription profiling of yeast transformed with five deleterious BRCA1 variants

Project description:In order to investigate the molecular mechanisms activated by deleterious BRCA1 variants in yeast, the RNA obtained from yeast cells transformed with five variants exhibiting a phenotypic effect, either on proliferation and/or on HR was hybridized on microarrays in comparison with the RNA from cells transformed with wild-type BRCA1

2009-03-31 | E-MEXP-1867 | biostudies-arrayexpress

RNASeq of ten human breast cancer cell lines

Project description:In order to identify new targets for basal-like breast cancers, we performed RNA-Seq of 10 breast cancer cell lines. Basal-like cell lines (MDAMB231, MDAMB436, HCC1937, SUM149, SUM1315 and MCF10A) were compared to luminal cell lines (MCF7 and T47D). Moreover we could also study BRCA1 influence on transcriptome of basal-like breast cancer. 4 of our cell lines are indeed BRCA1 mutated (MDAMB436, HCC1937, SUM149 and SUM1315) and we also developed 2 cell lines that come from the BRCA1 mutated SUM1315 cell line stably transfected with empty LXSN plasmid (SUM1315-LXSN) or with a BRCA1 coding plasmid (SUM1315-BRCA1).

2017-02-14 | E-MTAB-5465 | biostudies-arrayexpress

CGH profiles of primary breast carcinomas from HBOC (Hereditary Breast and Ovarian Cancer) families

Project description:89 tumors from women that were eligible for, and subjected to, routine diagnostic testing according to the HBOC criteria but were negative for pathogenic BRCA1/2-mutations or carried an UV in either BRCA1/2 A BRCA2-classifier was built using array-CGH profiles of 28 BRCA2-mutated and 28 sporadic breast tumors. The classifier was validated on an independent group of 19 BRCA2-mutated and 19 sporadic breast tumors. Subsequently, we tested 89 breast tumors from suspected hereditary breast (and ovarian) cancer (HBOC) families, in which either no BRCA1/2 mutation or an UV had been found by routine diagnostics.

2010-07-05 | E-GEOD-22481 | biostudies-arrayexpress

Gene expression by antigen activated OT-I T cells in vivo in the presence and absence of IL-2

Project description:Much is known concerning the cellular and molecular basis for CD8+ T memory immune responses. Nevertheless, conditions that selectively support memory generation have remained elusive. Here we show that an immunization regimen that delivers TCR signals through a defined antigenic peptide, inflammatory signals through LPS, and growth and differentiation signals through the IL-2R initially favors antigen-specific CD8+ T cells to rapidly and substantially develop into tissue-residing T effector-memory cells by TCR transgenic OVA-specific OT-I CD8+ T cells. Amplified CD8+ T memory development depends upon a critical frequency of antigen-specific T cells and direct responsiveness to IL-2. A homologous prime-boost immunization protocol with transiently enhanced IL-2R signaling in normal mice led to persistent polyclonal antigen-specific CD8+ T cells that supported protective immunity to Listeria monocytogenes. These results identify a general approach for amplified T memory development that may be useful to optimize vaccines aimed at generating robust cell-mediated immunity. Gene expression analysis was performed for OT-I T cells on day 3 and day 5 after activation with ovalbumin and LPS in vivo with and without treatment with IL-2 using an agonists IL-2/anti-IL-2 complexes (IL2/Jes-6.1) OT-I T cells were purified and adoptively transferred into congenic syngenic mice. 24 hours later mice were immunization with ovalbumin and LPS. 24 hr later some mice received agonist IL2/anti-IL2. 3 and 5 days after immunization, the activated OT-I T cells were purifed by FACS and total RNA was isolated for genome wide expression analysis using Affymetrix Mouse Gene ST1.0 arrays

2012-10-03 | E-GEOD-39110 | biostudies-arrayexpress

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