{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:11:08Z","timestamp":1790428268180,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017964","name":"Tianjin Health Technology Project","doi-asserted-by":"publisher","award":["TJWJ2023QN040"],"award-info":[{"award-number":["TJWJ2023QN040"]}],"id":[{"id":"10.13039\/100017964","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: Colorectal cancer (CRC) is the third most common cancer worldwide, with liver metastasis being the leading cause of mortality. De novo fatty acid synthesis plays a critical role in CRC progression and metastasis. Bufalin, a cardiotonic steroid isolated from toad skin, has demonstrated anticancer activity in multiple preclinical models. However, the mechanisms underlying its suppression of CRC metastasis and modulation of fatty acid synthesis remain to be elucidated. Methods: The effects of bufalin on CRC cell proliferation, migration, and apoptosis were assessed via colony formation, wound healing, and flow cytometry assays. Transcriptome analysis identified bufalin-affected pathways, with changes in gene and protein expression. FASN protein levels were quantified using ELISA. Results: Bufalin inhibited proliferation and migration of CRC cells and induced the apoptosis of LoVo and HCT8 cells. Transcriptome analysis highlighted lipid metabolism pathways as potential mediators of bufalin\u2019s anti-metastatic activity. Notably, bufalin reduced the expression of fatty acid synthase (FASN) and suppressed CRC metastasis. In vivo experiments demonstrated that bufalin attenuated CRC progression and liver metastasis by inhibiting de novo fatty acid synthesis through the PI3K\/AKT-mediated SREBP1\/FASN pathway. Conclusions: Bufalin inhibits de novo fatty acid synthesis via the PI3K\/AKT-mediated SREBP1\/FASN pathway, suppressing CRC progression and liver metastasis.<\/jats:p>","DOI":"10.3390\/molecules30173634","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T14:53:01Z","timestamp":1757083981000},"page":"3634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bufalin Suppresses Colorectal Cancer Liver Metastasis by Inhibiting De Novo Fatty Acid Synthesis via the PI3K\/AKT-Mediated SREBP1\/FASN Pathway"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3892-8707","authenticated-orcid":false,"given":"Wenwen","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China"},{"name":"Tianjin Integrative Traditional Chinese and Western Medicine Oncology Institute, Tianjin 300121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1868-0039","authenticated-orcid":false,"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suying","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junshi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology Center, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7910-5193","authenticated-orcid":false,"given":"Bowei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2063-5631","authenticated-orcid":false,"given":"Chunze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China"},{"name":"The Institute of Translational Medicine, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China"},{"name":"Tianjin Institute of Coloproctology, Tianjin 300121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1038\/s41591-024-03083-7","article-title":"Botensilimab plus balstilimab in relapsed\/refractory microsatellite stable metastatic colorectal cancer: A phase 1 trial","volume":"30","author":"Bullock","year":"2024","journal-title":"Nat. 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