{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:25:59Z","timestamp":1787199959021,"version":"build-2736575974"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To evaluate the apoptosis-modulating and therapeutic efficacy of hispidulin-loaded carboxymethyl cellulose nanoparticles (HIS-CMC NPs) in mammary carcinogenesis through\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      investigations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Apoptotic activity of HIS-CMC NPs was assessed in MCF-7 cells using cell viability, intracellular reactive oxygen species (ROS), DAPI, acridine orange\/ethidium bromide (AO\/EB), and Annexin-V\/PI flow cytometry assays. Therapeutic efficacy was further examined in a DMBA-induced mammary carcinogenesis BALB\/c mice model through haematological, biochemical, histopathological, immunohistochemical and oxidative stress analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HIS-CMC NPs significantly reduced MCF-7 cell viability and exhibited a lower IC\n                      <jats:sub>50<\/jats:sub>\n                      value (34.36 \u00b1 1.66 \u03bcg\/mL) than free hispidulin. Enhanced ROS generation, chromatin condensation, nuclear fragmentation, membrane destabilisation, and increased late apoptotic cell populations confirmed ROS-mediated apoptosis.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , HIS-CMC NPs improved haematological and biochemical parameters, restored tissue architecture, downregulated\n                      <jats:italic>Ki67<\/jats:italic>\n                      and\n                      <jats:italic>Nrf2<\/jats:italic>\n                      expression, restored antioxidant enzyme activities, and reduced lipid peroxidation and lactate dehydrogenase levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HIS-CMC NPs effectively promoted ROS-dependent apoptosis and attenuated oxidative stress in mammary carcinogenesis. The nanoformulation demonstrated enhanced therapeutic efficacy with reduced systemic toxicity, highlighting its potential as a promising nanotherapeutic strategy for breast cancer management. HIS-CMC NPs, mammary carcinogenesis, apoptosis, oxidative stress, proliferation biomarkers, immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1915182","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:15:41Z","timestamp":1787199341000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic efficacy of hispidulin-loaded carboxymethyl cellulose nanoparticles against mammary carcinogenesis through ROS-mediated apoptosis and tissue remodelling"],"prefix":"10.3389","volume":"16","author":[{"given":"Vrushali Manoj","family":"Hadkar","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT)","place":["Vellore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinnadurai 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