{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:25:52Z","timestamp":1786951552943,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Non\u2010small cell lung cancer (NSCLC) progression is strongly influenced by tumor\u2010associated macrophages (TAMs), which frequently acquire an M2\u2010like phenotype that promotes proliferation, epithelial\u2010mesenchymal transition (EMT), angiogenesis, stemness, and therapy resistance. Previous studies from our group established the direct cytostatic and macrophage\u2010polarizing effects of the synthetic coumarin derivative 4\u2010fluorophenylacetamide\u2010acetyl coumarin (4\u2010FPAC), including ROS\u2010mediated apoptosis, G0\/G1 cell\u2010cycle arrest, suppression of EMT\u2010associated signaling in A549 cells, and promotion of M1\u2010like macrophage polarization. In the present study, we investigated whether 4\u2010FPAC\u2010modulated TAM\u2010derived conditioned media could suppress tumor\u2010promoting behavior in A549 NSCLC cells. THP\u20101 monocytes were differentiated into macrophages and polarized using A549\u2010conditioned medium to generate TAM\u2010like macrophages. These TAMs were subsequently treated with 4\u2010FPAC, and conditioned media from control or treated TAMs were applied to A549 cells to evaluate macrophage\u2010associated anti\u2010tumor effects. MTT analysis further showed that direct exposure of A549 cells to 4\u2010FPAC under TAM\u2010CM\u2010supported conditions reduced cell viability in a dose\u2010dependent manner. Functional assays demonstrated that conditioned media derived from 4\u2010FPAC\u2010treated TAMs significantly reduced A549 proliferation, inhibited migration and invasion, and impaired angiogenic responses in a chick chorioallantoic membrane model. Flow cytometry revealed G0\/G1 cell\u2010cycle arrest and reduced NANOG\u2010positive stem\u2010like cells, while DNA fragmentation and TUNEL assays confirmed enhanced apoptosis. Mechanistically, qRT\u2010PCR and immunoblotting demonstrated EMT reversal, suppression of AKT signaling, VEGF\u03b1, IL8, OCT3\/4, and NANOG, and upregulation of p21, p53, and caspase\u20103\/cleaved caspase\u20103. Collectively, these findings demonstrate that 4\u2010FPAC directly suppresses A549 viability under TAM\u2010CM\u2010supported conditions and modulates TAM\u2010derived conditioned\u2010media activity, highlighting its potential to target both tumor cells and tumor\u2010macrophage interactions within the NSCLC microenvironment.<\/jats:p>","DOI":"10.1002\/jbt.71066","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:15:17Z","timestamp":1786360517000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["4\u2010FPAC\u2010Modulated Tumor\u2010Associated Macrophage Conditioned Media Suppresses Malignant Phenotypes and Promotes Cell\u2010Cycle Arrest and Apoptosis in NSCLC"],"prefix":"10.1002","volume":"40","author":[{"given":"Anjali","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda Vadodara 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