SWATH-MS based quantitative proteomics analysis reveals that curcumin alters the metabolic enzyme profile of CML cells by affecting the activity of miR-22/IPO7/HIF-1α axis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30045750", "kind": "science-record", "revision": 6, "content_hash": "sha256:35fa22946c06c2910e4c0203c9365005624bc88a34a6d8b10fa688d2f57366ac", "created_at": "2026-11-01T15:40:36Z", "updated_at": "2026-11-01T21:21:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "SWATH-MS based quantitative proteomics analysis reveals that curcumin alters the metabolic enzyme profile of CML cells by affecting the activity of miR-22/IPO7/HIF-1α axis.", "doi": "10.1186/s13046-018-0843-y", "pmid": "30045750", "authors": ["Francesca Monteleone", "Simona Taverna", "Riccardo Alessandro", "Simona Fontana"], "journal": "Journal of experimental & clinical cancer research : CR", "year": 2018, "abstract": "BACKGROUND: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, resulting from the t(9;22) chromosomal translocation. Imatinib (gleevec, STI-571) is a selective inhibitor of BCR-ABL activity highly effective in the treatment of CML. However, even though almost all CML patients respond to treatment with imatinib or third generation inhibitors, these drugs are not curative and need to be taken indefinitely or until patients become resistant. Therefore, to get a definitive eradication of leukemic cells, it is necessary to find novel therapeutic combinations, for achieving greater efficacy and fewer side effects. Curcumin is an Indian spice with several therapeutic properties: anti-oxidant, analgesic, anti-inflammatory, antiseptic and anti-cancer. In cancer disease, it acts by blocking cell transformation, proliferation, and invasion and by inducing cell apoptosis.\nMETHODS: In the present study, the effect of a sub-toxic dose of curcumin on K562 cells was evaluated by using the technique of Sequential Window Activation of All Theoretical Mass Spectra (SWATH-MS). Bioinformatic analysis of proteomic data was performed to highlight the pathways mostly affected by the treatment. The involvement of Hypoxia inducible factor 1 α (HIF-1α) was assayed by evaluating its activation status and the modulation of importin 7 (IPO7) and miR-22 was assessed by quantitative PCR and western blot analysis. Finally, K562 cells transfected with miR-22 inhibitor were used to confirm the ability of curcumin to elicit miR-22 expression.\nRESULTS: Our findings revealed that the most relevant effect induced by curcumin was a consistent decrease of several proteins involved in glucose metabolism, most of which were HIF-1α targets, concomitant with the up-regulation of functional and structural mitochondrial proteins. The mechanism by which curcumin affects metabolic enzyme profile was associated with the reduction of HIF-1α activity, due to the miR-22-mediated down-regulation of IPO7 expression. Finally, the ability of curcumin to enhance in vitro the efficiency of imatinib was reported.\nCONCLUSIONS: In summary, our data indicates that the miR-22/IPO7/HIF-1α axis may be considered as a novel molecular target of curcumin adding new insights to better define therapeutic activity and anticancer properties of this natural compound. The MS proteomic data have been deposited to the ProteomeXchange with identifier <PXD007771>.", "claims": [{"id": "claim-method", "statement": "The protein list with FDR lower than 5% generated by analyzing SWATH data with PeakView 2.2, was exported to MarkerView 1.2.1 (AB SCIEX; Framingham, US) for normalization of protein intensity (peak area) using the total area sums algorithm and t-test analysis [13, 16]. Mean of all biological and technical replicates was used to compare proteins of Ctrl-K562 and Curcu-K562. Fold Change (FC) Curcu-K562 vs Ctrl-K562 thresholds at ±1.5 with a corrected p-value inferior to 0.05 were used to consider a protein up or down-regulated. GraphPad Prism 7.00 for Windows was used for (i) performing the p-value Benjamini-Yekutieli (BY-Pvalue) correction (13); (ii) to make a volcano plot scaling in which the FC was transformed using the log2 function, so that the data is centered on zero, while the BY corrected p-value was −log10 transformed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30045750", "locator": "sections[8] \"Statistical analysis, gene ontology analysis, functional networks and pathway mapping\" paragraph 2", "quote": "The protein list with FDR lower than 5% generated by analyzing SWATH data with PeakView 2.2, was exported to MarkerView 1.2.1 (AB SCIEX; Framingham, US) for normalization of protein intensity (peak area) using the total area sums algorithm and t-test analysis [13, 16]. Mean of all biological and technical replicates was used to compare proteins of Ctrl-K562 and Curcu-K562. Fold Change (FC) Curcu-K562 vs Ctrl-K562 thresholds at ±1.5 with a corrected p-value inferior to 0.05 were used to consider a protein up or down-regulated. GraphPad Prism 7.00 for Windows was used for (i) performing the p-value Benjamini-Yekutieli (BY-Pvalue) correction (13); (ii) to make a volcano plot scaling in which the FC was transformed using the log2 function, so that the data is centered on zero, while the BY corrected p-value was −log10 transformed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) [14] via the PRIDE partner repository [15] with the dataset identifier <PXD007771>.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30045750", "locator": "sections[7] \"SWATH-MS analysis and targeted data extraction\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) [14] via the PRIDE partner repository [15] with the dataset identifier <PXD007771>."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30045750"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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(http://proteomecentral.proteomexchange.org) [14] via the PRIDE partner repository [15] with the dataset identifier <PXD007771>.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) [14] via the PRIDE partner repository [15] with the dataset identifier <PXD007771>.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "SWATH-MS based quantitative proteomics analysis reveals that curcumin alters the metabolic enzyme profile of CML cells by affecting the activity of miR-22/IPO7/HIF-1α axis.", "resolution_checked_at": "2026-10-31T18:28:56Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, 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"Proteins implicated in nuclear import/export identified by MS in K562cells", "structure": {"pmcid": "PMC6060558", "section_index": 17, "section_title": "Effects of curcumin on HIF-1α activity and IPO7 expression", "row_count": 15, "column_count": 7}, "table": {"label": "Table 4", "caption": "Proteins implicated in nuclear import/export identified by MS in K562cells", "rows": [["UniProt Accession Number", "UniProt Entry Name", "Gene Name", "Protein Name", "Fold Change (Curcu-K562 vs Ctrl K562)", "p-Value", "BY-Pvalue"], ["O00410", "IPO5_HUMAN", "IPO5", "Importin-5", "-1.530", "0.002162", "0.0383"], ["O95373", "IPO7_HUMAN", "IPO7", "Importin-7", "-2.332", "0.000107", "0.0030"], ["Q96P70", "IPO9_HUMAN", "IPO9", "Importin-9", "−2.241", "0.121934", "> 0.999"], ["P52292", "IMA1_HUMAN", "KPNA2", "Importin subunit alpha-1", "−1.040", "0.040815", "0.5065"], ["O00629", "IMA3_HUMAN", "KPNA4", "Importin subunit alpha-3", "−1.279", "0.002692", "0.0465"], ["O00505", "IMA4_HUMAN", "KPNA3", "Importin 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Mean of all biological and technical replicates was used to compare proteins of Ctrl-K562 and Curcu-K562. Fold Change (FC) Curcu-K562 vs Ctrl-K562 thresholds at ±1.5 with a corrected p-value inferior to 0.05 were used to consider a protein up or down-regulated. GraphPad Prism 7.00 for Windows was used for (i) performing the p-value Benjamini-Yekutieli (BY-Pvalue) correction (13); (ii) to make a volcano plot scaling in which the FC was transformed using the log2 function, so that the data is centered on zero, while the BY corrected p-value was −log10 transformed."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["ols_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ols."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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