{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:43:27Z","timestamp":1791287007967,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sirtuin 1 (SIRT1), a member of histone deacetylase III family, plays a pivotal role in mediating chemoresistance in several cancers, including breast cancer. However, the molecular mechanism by which the deregulated SIRT1 promotes doxorubicin (Dox) resistance is still elusive. Here, we showed that the cell proliferation rates and invasive properties of MDA\u2010MB\u2010231 breast cancer cells were increased from low\u2010 to high\u2010Dox\u2010resistant cells. In agreement, severe combined immunodeficiency disease (SCID) mice bearing labeled MDA\u2010MB\u2010231<jats:sup>high Dox\u2010Res<\/jats:sup> cells showed significantly higher tumor growth, angiogenesis, and metastatic ability than parental MDA\u2010MB\u2010231 cells. Interestingly, the levels of SIRT1 and glutathione (GSH) were positively correlated with the degree of Dox\u2010resistance. Dox\u2010induced SIRT1 promoted NRF2 nuclear translocation with an accompanying increase in the antioxidant response element promotor activity and GSH levels. In contrast, inhibition of SIRT1 by EX527 greatly reversed these events. More so, Dox\u2010resistance\u2010induced pro\u2010proliferative, proangiogenic, and invasive effects were obviated with depletion of either SIRT1 or GSH. Together, Dox\u2010induced SIRT1 promotes dysregulation of redox homeostasis leading to breast cancer chemoresistance, tumor aggressiveness, angiogenesis, and metastasis.<\/jats:p>","DOI":"10.1002\/mc.23809","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T18:09:26Z","timestamp":1723572566000},"page":"2291-2304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["SIRT1 promotes doxorubicin\u2010induced breast cancer drug resistance and tumor angiogenesis via regulating GSH\u2010mediated redox homeostasis"],"prefix":"10.1002","volume":"63","author":[{"given":"Shashikanta","family":"Sahoo","sequence":"first","affiliation":[{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology Hyderabad India"},{"name":"Academy of Scientific and Innovative Research Ghaziabad 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