{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:08:41Z","timestamp":1772712521739,"version":"3.50.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"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. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Leukemia is a malignant hematologic disease that poses a serious threat to human health. Realgar-Indigo Naturalis formula (RIF), a traditional Chinese medicine formula, have demonstrated anti-tumor activity, but its mechanisms of action remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to establish a zebrafish HL-60 tumor transplantation model to investigate the anti-leukemic effects of RIF and explore its underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The zebrafish HL-60 tumor transplantation model was established, with RIF as the intervention drug and all-trans retinoic acid (ATRA) as the control. Anti-tumor efficacy was assessed via pharmacodynamic analysis. Transcriptomic analysis further elucidated gene expression profiles, differentially expressed genes, and relevant biological pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RIF significantly reduced tumor cell fluorescence intensity, demonstrating anti-tumor efficacy. Additionally, it improved HL-60-induced liver damage in zebrafish, as evidenced by a reduction in fatty vacuolar degeneration in liver tissue. Transcriptomic analysis revealed that ATRA mainly affected the FoxO signaling pathway, PI3K-Akt signaling pathway, apoptosis, and complement and coagulation cascades in leukemia treatment. RIF primarily influenced the ubiquitin-proteasome system, ferroptosis, and glutathione metabolism. The combination of ATRA and RIF also affected autophagosome and lysosome pathways, in addition to the aforementioned pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RIF exhibit significant anti-tumor effects through modulation of multiple pathways. This study provides a theoretical foundation for the potential clinical application of RIF in leukemia treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1619352","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T08:53:32Z","timestamp":1752828812000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of realgar-indigo naturalis formula on a zebrafish tumor xenograft model induced by human acute promyelocytic leukemia cells: antitumor activity, hepatotoxicity, and transcriptomic analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Donghan","family":"Bai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyue","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaochu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remy","family":"Macdonald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziwen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shumin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanxi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/s41375-023-02117-2","article-title":"Mitochondrial regulation of GPX4 inhibition\u2013mediated ferroptosis in acute myeloid leukemia","volume":"38","author":"Akiyama","year":"2024","journal-title":"Leukemia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1542560","DOI":"10.3389\/fphar.2025.1542560","article-title":"The outcast of medicine: metals in medicine--from traditional mineral medicine to metallodrugs","volume":"16","author":"Bai","year":"2025","journal-title":"Front. 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