{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:01:57Z","timestamp":1785391317709,"version":"3.55.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bufothionine, a major bioactive component of dried toad skin, has shown anti-tumor potential. However, its efficacy and underlying mechanisms in colorectal cancer (CRC) remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the therapeutic potential of bufothionine and its underlying mechanisms against CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Anti-tumor efficacy was assessed using\n                      <jats:italic>in vitro<\/jats:italic>\n                      (CCK-8, migration assays) and\n                      <jats:italic>in vivo<\/jats:italic>\n                      (HT-29 xenograft) models. Network pharmacology, molecular docking and molecular dynamics simulations were employed to predict targets. Mechanisms were validated by biochemical assays, Western blot, IHC, and qPCR, with ferrostatin-1 applied to confirm ferroptosis specificity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bufothionine significantly inhibited HT-29 cell proliferation and migration. Integrated network pharmacology and computational modeling identified p53 and STAT3 as core targets, with potential interactions predicted between bufothionine and key ferroptosis regulators (including SLC7A11).\n                      <jats:italic>In vitro<\/jats:italic>\n                      , bufothionine induced ferroptosis, characterized by increased Fe\n                      <jats:sup>2+<\/jats:sup>\n                      , ROS, and MDA levels, and a decreased GSH\/GSSG ratio; these effects were partially reversed by ferrostatin-1.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , bufothionine reduced tumor weight indices, improved liver function by attenuating AST and ALP elevations without hepatosplenic toxicity, and regulated inflammatory cytokines. Mechanistically, bufothionine suppressed inflammatory activation (NLRP3, IL-1\u03b2), inhibited STAT3 phosphorylation, and modulated p53 activity, leading to the subsequent inhibition of the SLC7A11\/GPX4 axis in both cells and tumor tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bufothionine suppresses CRC by the STAT3\/p53\/SLC7A11 signaling axis in a manner associated with ferroptosis, suggesting its potential as a therapeutic agent for colorectal cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1885072","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:39:12Z","timestamp":1785389952000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bufothionine inhibits colorectal cancer progression via the STAT3\/p53\/SLC7A11 signaling axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruifang","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeye","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingru","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.2147\/CPAA.S153780","article-title":"Pramlintide, an antidiabetic, is antineoplastic in colorectal cancer and synergizes with conventional chemotherapy","volume":"10","author":"Al-Keilani","year":"2018","journal-title":"Clin. 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