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Nano-encapsulation in liposomes enhances its therapeutic potential by improving protein stability, bioavailability, and sustained release. Previous studies demonstrated that nano-encapsulated tarin induces cell cycle arrest, migration inhibition, apoptosis, and autophagy in triple-negative breast cancer cells; however, the molecular mechanisms underlying these effects remain poorly understood. To investigate the proteomic response elicited by nano-encapsulated tarin, MDA-MB-231 cells were treated for 24 and 48 h. Methods: Intracellular proteins were extracted, digested with trypsin, and analyzed by label-free LC-2D-MS\/MS using HDMSE acquisition. Differentially expressed proteins were identified and quantified using the Progenesis QI platform, and then functional classification and pathway enrichment analyses were performed. Results: A total of 2818 proteins were identified, of which 2150 displayed time-dependent modulation following treatment. After 24 h, cells exhibited an adaptive stress response profile characterized by increased DNA repair proteins (CHEK1, CDK12), migration\/remodeling factors (LAMA4, CTTN, A2M), and immune\/cell cycle regulators (PER2, HLA-B), while antioxidant proteins (SOD1, GPX1) and BRCA1 were reduced, indicating oxidative stress and DNA damage. After 48 h, the proteomic profile shifted toward cell death, with increased PARK7, OPA1, ATL3, and CASP8 expression, disruption of DNA repair and cell cycle regulators (CHEK1, CDK12, MSH6, KIF2C), and decreased migration-related proteins (LAMA4, CTTN, ITGB3, A2M). Conclusions: Nano-encapsulated tarin promotes a time-dependent transition from early adaptive stress responses to apoptosis, autophagy, cell cycle disruption, and loss of migratory capacity. These findings provide novel insights into the molecular mechanisms underlying tarin antitumoral activity and support its potential as a promising therapeutic strategy against triple-negative breast cancer.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091123","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:23:37Z","timestamp":1788773017000},"page":"1123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protein Expression Dynamics in Breast Cancer Cells Exposed to Nano-Encapsulated Tarin, the Taro Lectin"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4672-0674","authenticated-orcid":false,"given":"Raiane V.","family":"Cardoso","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos 149, Sala 545, Cidade Universit\u00e1ria, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9008-9904","authenticated-orcid":false,"given":"Patricia R.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos 149, Sala 545, Cidade Universit\u00e1ria, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyntia S.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos 149, Sala 545, Cidade Universit\u00e1ria, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8592-9670","authenticated-orcid":false,"given":"Yuri P.","family":"Souza","sequence":"additional","affiliation":[{"name":"Unidade de Espectrometria de Massas e Prote\u00f4mica, Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Cidade Universit\u00e1ria, Rio de Janeiro 21941-599, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4194-7404","authenticated-orcid":false,"given":"D\u00e1rio E.","family":"Kalume","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Instituto Oswaldo Cruz, Av. Brasil 4365, Manguinhos, Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2721-0238","authenticated-orcid":false,"given":"Giovani Carlo","family":"Verissimo da Costa","sequence":"additional","affiliation":[{"name":"Instituto de Sa\u00fade, Universidade Federal Fluminense, Rua Dr. Silvio Henrique Braune 22, Centro, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6133-5080","authenticated-orcid":false,"given":"Carlos A.","family":"Conte-Junior","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Av. 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