{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:53:33Z","timestamp":1790189613616,"version":"4.1.0"},"reference-count":80,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Current toxicology and cancer biology investigations have focused on developing alternative models that better recapitulate the in vivo architecture of tissues and organs. The present study evaluated the anticancer effects of the flavone cirsimarin, which presented successful antitumor activity on breast tumor cells. We assessed the impact of flavone on cell viability, proliferation, and migration, as well as on DNA integrity and modulation of related cellular pathways. In the 2D model, cirsimarin reduced cell viability at concentrations \u2265\u200980\u2009\u03bcM after 24\u2009h of treatment (resazurin assay), selectively in A549 cells compared to MRC\u20105 non\u2010tumor cells. Apoptosis was induced at concentrations \u2265\u200940\u2009\u03bcM, and clonogenicity was reduced by approximately 50% only at 160\u2009\u03bcM. In the wound healing assay, cirsimarin (1\u201380\u2009\u03bcM) completely inhibited cell migration and induced DNA damage (comet assay). These apoptotic and anti\u2010migratory effects were associated with the downregulation of key genes involved in cell proliferation, death, and extracellular matrix remodeling, including\n                    <jats:italic>TNF\u2010\u03b1<\/jats:italic>\n                    (0.32\u2010fold),\n                    <jats:italic>TP53<\/jats:italic>\n                    (0.17\u2010fold),\n                    <jats:italic>MMP\u20102<\/jats:italic>\n                    (0.18\u2010fold),\n                    <jats:italic>MMP\u20109<\/jats:italic>\n                    (0.43\u2010fold), and\n                    <jats:italic>MMP\u201011<\/jats:italic>\n                    (0.04\u2010fold), as revealed by RT\u2010qPCR analysis. In the 3D model, after 216\u2009h of treatment, cirsimarin reduced cell viability (\u2265\u200940\u2009\u03bcM) and spheroid area (\u2265\u200980\u2009\u03bcM) while antimigratory effects were observed only in the highest concentration evaluated (160\u2009\u03bcM). These findings could indicate a potential reduction in lung tumor growth and metastasis, warranting further investigation, particularly of the antimetastatic effect of this flavone.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70772","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T06:02:26Z","timestamp":1773122546000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Modulatory Effects of Cirsimarin on Lung Cancer A549 Cells Migration in 2D and 3D Cultures Involves Transcriptional Regulation of Metalloproteinases"],"prefix":"10.1002","volume":"40","author":[{"given":"Anna Gabriele Prado dos","family":"Santos","sequence":"first","affiliation":[{"name":"Department of General Biology, Center of Biological Sciences State University of Londrina (UEL) Londrina Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celina Yung\u2010Ai Lin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of General Biology, Center of Biological Sciences State University of Londrina (UEL) Londrina Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9rica Rom\u00e3o","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of General Biology, Center of Biological Sciences State University of Londrina (UEL) Londrina Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andresa Hiromi","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of General Biology, Center of Biological Sciences State University of Londrina (UEL) Londrina Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Lu\u00eds","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences University of S\u00e3o Paulo (ICB\/USP) S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Neuro\u2010Oncology Branch, Center for Cancer Research, National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Ant\u00f4nio Silva","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Exact Sciences and Technology Federal University of Maranh\u00e3o (UFMA) S\u00e3o Lu\u00eds Maranh\u00e3o Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Bispo Pinheiro","family":"Camara","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Exact Sciences and Technology Federal University of Maranh\u00e3o (UFMA) S\u00e3o Lu\u00eds Maranh\u00e3o Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3578-1869","authenticated-orcid":false,"given":"Cl\u00e1udia Quintino da","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Exact Sciences and Technology Federal University of Maranh\u00e3o (UFMA) S\u00e3o Lu\u00eds Maranh\u00e3o Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3288-7331","authenticated-orcid":false,"given":"Sabine A. 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