{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:36:59Z","timestamp":1788629819772,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Research Plan of the National Natural Science Foundation of China","award":["92359202"],"award-info":[{"award-number":["92359202"]}]},{"name":"Major Research Plan of the National Natural Science Foundation of China","award":["2024YFC3405500"],"award-info":[{"award-number":["2024YFC3405500"]}]},{"name":"Major Research Plan of the National Natural Science Foundation of China","award":["NCTIB2022HS01016"],"award-info":[{"award-number":["NCTIB2022HS01016"]}]},{"name":"Major Research Plan of the National Natural Science Foundation of China","award":["XK2023-21"],"award-info":[{"award-number":["XK2023-21"]}]},{"name":"National Key Research and Development Program","award":["92359202"],"award-info":[{"award-number":["92359202"]}]},{"name":"National Key Research and Development Program","award":["2024YFC3405500"],"award-info":[{"award-number":["2024YFC3405500"]}]},{"name":"National Key Research and Development Program","award":["NCTIB2022HS01016"],"award-info":[{"award-number":["NCTIB2022HS01016"]}]},{"name":"National Key Research and Development Program","award":["XK2023-21"],"award-info":[{"award-number":["XK2023-21"]}]},{"name":"\u201cOpen Competition to Select the Best Candidates\u201d Key Technology Program for Nucleic Acid Drugs of NCTIB","award":["92359202"],"award-info":[{"award-number":["92359202"]}]},{"name":"\u201cOpen Competition to Select the Best Candidates\u201d Key Technology Program for Nucleic Acid Drugs of NCTIB","award":["2024YFC3405500"],"award-info":[{"award-number":["2024YFC3405500"]}]},{"name":"\u201cOpen Competition to Select the Best Candidates\u201d Key Technology Program for Nucleic Acid Drugs of NCTIB","award":["NCTIB2022HS01016"],"award-info":[{"award-number":["NCTIB2022HS01016"]}]},{"name":"\u201cOpen Competition to Select the Best Candidates\u201d Key Technology Program for Nucleic Acid Drugs of NCTIB","award":["XK2023-21"],"award-info":[{"award-number":["XK2023-21"]}]},{"name":"Joint Project of Biomedical Translational Engineering Research Center of Beijing University of Chemical Technology","award":["92359202"],"award-info":[{"award-number":["92359202"]}]},{"name":"Joint Project of Biomedical Translational Engineering Research Center of Beijing University of Chemical Technology","award":["2024YFC3405500"],"award-info":[{"award-number":["2024YFC3405500"]}]},{"name":"Joint Project of Biomedical Translational Engineering Research Center of Beijing University of Chemical Technology","award":["NCTIB2022HS01016"],"award-info":[{"award-number":["NCTIB2022HS01016"]}]},{"name":"Joint Project of Biomedical Translational Engineering Research Center of Beijing University of Chemical Technology","award":["XK2023-21"],"award-info":[{"award-number":["XK2023-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer (BC) remains a significant therapeutic challenge, necessitating novel agents with multi-target efficacy. Here, we demonstrate that triptophenolide (TRI), a bioactive compound from Tripterygium wilfordii, exerts potent anti-BC activity across hormone-responsive (MCF-7) and triple-negative (MDA-MB-231) subtypes. In vitro, TRI inhibited proliferation in a concentration-dependent manner, with IC50 values decreasing from 180.3 \u03bcg\/mL (24 h) to 127.2 \u03bcg\/mL (48 h) in MCF-7 cells, and from 322.5 \u03bcg\/mL to 262.1 \u03bcg\/mL in MDA-MB-231 cells. TRI treatment induced G1-phase arrest in both breast cancer subtypes, increasing the G1 population by 22.27% in MCF-7 cells and 10.64% in MDA-MB-231 cells. Concurrently, TRI triggered apoptosis, elevating apoptotic rates from 3.36% to 9.78% in MCF-7 cells and from 7.01% to 17.02% in MDA-MB-231 cells. These effects were associated with the significant upregulation of pro-apoptotic proteins BAX, BAK1, BIM, and cytochrome c (CYCS). Notably, TRI suppressed migration by 61.5% (MCF-7) and 71.5% (MDA-MB-231). In vivo, TRI treatment inhibited MCF-7 xenograft growth and reduced tumor volume (1207.5 vs. 285 mm3) and weight (0.22 vs. 0.1 g), while extending the survival time of tumor-bearing mice from 14\u201320 days to 24 days. These results position TRI as a promising lead therapeutic candidate against diverse BC subtypes, with mechanistic versatility surpassing single-target agents.<\/jats:p>","DOI":"10.3390\/ijms26125469","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"5469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multi-Targeted Anti-Cancer Effects of Triptophenolide in Hormone-Responsive and Triple-Negative Breast Cancer Models"],"prefix":"10.3390","volume":"26","author":[{"given":"Zufa","family":"Sabeel","sequence":"first","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangshuai","family":"Chai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ying","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangyang","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2856-7167","authenticated-orcid":false,"given":"Zhao","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12943-025-02258-1","article-title":"Lipid metabolic reprograming: The unsung hero in breast cancer progression and tumor microenvironment","volume":"24","author":"Wan","year":"2025","journal-title":"Mol. 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