{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T02:59:25Z","timestamp":1782442765425,"version":"3.54.5"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"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>\n                      Colorectal cancer (CRC) progression involves complex interactions between tumor cells, immune evasion, and metabolic reprogramming. Cryptotanshinone (CTS), a bioactive diterpenoid from\n                      <jats:italic>Salvia miltiorrhiza<\/jats:italic>\n                      , has demonstrated anticancer potential, but its integrated effects on CRC remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      models to evaluate the therapeutic effects and mechanism of CTS. Using MC38 cells and mouse-derived CRC organoids, we assessed its impact on proliferation and apoptosis through CCK-8, clonogenic, and Annexin V\/PI assays. For\n                      <jats:italic>vivo<\/jats:italic>\n                      evaluation, a murine AOM\/DSS-induced CRC model was established and administered CTS via intraperitoneal injection for 8 weeks. Comprehensive analyses included histopathology, immune profiling by flow cytometry, 16S rRNA sequencing of gut microbiota, and LC-MS-based metabolomics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CTS exerted potent anti-CRC effects, suppressing tumor cell proliferation and inducing apoptosis\n                      <jats:italic>in vitro<\/jats:italic>\n                      . In AOM\/DSS-induced mice, CTS significantly inhibited tumor growth, ameliorated colon shortening and pathological damage, and reduced inflammation. Mechanistically, CTS alleviated T cell exhaustion, reversed metabolic dysregulation, and restored gut microbiota community structure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CTS effectively suppresses CRC progression. Its efficacy is associated with the coordinated modulation of the tumor-immune-microbiome axis, involving direct cytotoxicity, reduced PD-1+ T cell levels, and restructuring of the gut microbial community. These results highlight CTS as a promising multi-faceted therapeutic candidate and provide a preclinical rationale for its further development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1667500","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T06:29:28Z","timestamp":1765261768000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cryptotanshinone targets tumor-immune-microbiome axis to suppress colorectal cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhenya","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeneng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"438","DOI":"10.37201\/req\/056.2024","article-title":"Human intestinal microbiome: role in health and disease","volume":"37","author":"Cant\u00f3n","year":"2024","journal-title":"Rev. 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