{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:23:04Z","timestamp":1788535384433,"version":"build-2803163510"},"reference-count":82,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["31092"],"award-info":[{"award-number":["31092"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Recovery and Resilience Plan","award":["PNC0000003"],"award-info":[{"award-number":["PNC0000003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Melittin, the cytolytic peptide of honeybee venom, exhibits potent anticancer activity in triple-negative breast cancer (TNBC), yet the molecular programs underlying its cytotoxic effects remain incompletely defined. To address this gap, MDA-MB-231 TNBC cells were exposed to melittin at half-maximal inhibitory concentration(half IC50) and IC50 across early(0.5, 1, and 2 h), mid(3, 4 h), and late (12, 24 h) time windows. Proteomic profiling was performed using label-free data-independent acquisition(DIA) parallel accumulation\u2013serial fragmentation(PASEF). Approximately 5800 proteins were quantified, revealing distinct dose-dependent stress responses. An integrative exploratory framework combining time-resolved log2 fold-change trajectories, area-under-the-curve(AUC) based temporal prioritization, and independent heatmap visualization identified proteins associated with melittin-induced stress remodeling. Half IC50 exposure showed a transient stress-adaptive signature characterized by chromatin remodeling(HMGN2, H2AZ1), structural and RNA-associated buffering(LRRC7), and indirect mitochondrial quality-control signaling(CPAMD8, SPATA4), which progressively weakened over time. In contrast, IC50 treatment induced rapid chromatin remodeling dominated by histone H1 variants(H1.4, H1.2), early RNA instability(LRRC7), and late-stage cytoskeletal disassembly marked by MICAL3 induction, consistent with progression toward apoptosis. These trajectories paralleled dose-dependent apoptotic phenotypes. Overall, data suggest that melittin elicits dose- and time-dependent proteomic stress responses in TNBC cells and identify candidate trajectory-associated proteins and pathways linked to adaptive stress remodeling or progression toward cytotoxic collapse.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00241","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T14:22:46Z","timestamp":1786026166000},"page":"4704-4718","source":"Crossref","is-referenced-by-count":0,"title":["Time- and\nDose-Resolved DIA-PASEF Proteomics Maps\nthe Transition from Adaptive Stress to Apoptotic Collapse in Melittin-Treated\nMDA-MB-231 Cells"],"prefix":"10.1021","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9167-5061","authenticated-orcid":true,"given":"Farnaz","family":"Fatahian","sequence":"first","affiliation":[{"name":"Shahid Beheshti University , , ,","place":["Tehran, Iran, 1983969411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3543-0894","authenticated-orcid":true,"given":"Seyed Mohammad Jafar","family":"Seyed Golestan","sequence":"additional","affiliation":[{"name":"Shahid Beheshti University , , ,","place":["Tehran, Iran, 1983969411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-7768","authenticated-orcid":true,"given":"Clizia","family":"Chinello","sequence":"additional","affiliation":[{"name":"University of Milano Bicocca , , ,","place":["Vedano al Lambro, Italy, 20854"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Pagani","sequence":"additional","affiliation":[{"name":"University of Milano Bicocca , , ,","place":["Vedano al Lambro, Italy, 20854"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Rezadoost","sequence":"additional","affiliation":[{"name":"Shahid Beheshti University , , ,","place":["Tehran, Iran, 1983969411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6613-3936","authenticated-orcid":true,"given":"Hossein","family":"Behboudi","sequence":"additional","affiliation":[{"name":"Shahid Beheshti University , , ,","place":["Tehran, Iran, 1983969411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Ghassempour","sequence":"additional","affiliation":[{"name":"Shahid Beheshti University , , ,","place":["Tehran, Iran, 1983969411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6530-6113","authenticated-orcid":true,"given":"Andrew","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Milano Bicocca , , ,","place":["Vedano al Lambro, Italy, 20854"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"issue":"3","key":"2026090409133532900_cit1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN\nEstimates of Incidence and Mortality Worldwide for 36 Cancers in 185\nCountries","volume":"74","author":"Bray","year":"2024","journal-title":"Ca-Cancer J. 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