{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T08:08:33Z","timestamp":1780301313717,"version":"3.54.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515140169"],"award-info":[{"award-number":["2022A1515140169"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Prostate cancer often reaches bone, which poses a challenge in orthopedic oncology since few therapies directly suppress tumor growth in bone. Bruceine D (BD) is a quassinoid from Brucea javanica. It is known anticancer activity but its effects on prostate cancer have not been defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this paper, we studied BD\u2019s drug effects on PC-3 and C4-2B prostate cancer cells using CCK-8, colony formation, wound healing, and Transwell assays. We measured apoptosis by Annexin V-FITC\/PI staining and flow cytometry. RNA sequencing, Western Blotting and molecular docking were used to identify signaling pathways and potential targets. We evaluated BD\u2019s antitumor effects and toxicities in a subcutaneous xenograft model in nude mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BD inhibited proliferation, migration, invasion and induced apoptosis in prostate cancer cells in a time- and dose-dependent manner. Transcriptomic analysis showed BD downregulated PI3K\/AKT pathway components (PIK3AP1, PIK3C2B, PIK3CB, PIK3R2, AKT1) and CXCL16. Western blotting showed decreased expression of p-PI3K, p-AKT, PCNA, MMP9, CXCL16, BCL-2 and BAX. Molecular docking predicted favorable binding to these targets. BD (0,0.7 mg\/kg) reduced tumor volume by 87.4% without liver\/kidney toxicity, and reduced Ki-67, PCNA, MMP9, CXCL16 in tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BD reduced prostate cancer growth and motility by inhibiting PI3K\/AKT signaling and concomitantly downregulating CXCL16, and showed anti-tumor activity in a subcutaneous xenograft model with good safety. These results provide mechanistic information on skeletal metastasis in orthopedic oncology. Dedicated bone metastasis models need to be evaluated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1819854","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T07:55:41Z","timestamp":1780300541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bruceine D attenuates prostate cancer growth and motility by suppressing PI3K\/AKT signaling and downregulating CXCL16: implications for skeletal metastasis in orthopedic oncology"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiwei","family":"Chen","sequence":"first","affiliation":[{"name":"Foshan Clinical Medical School of Guangzhou University of Chinese Medicine","place":["Foshan, China"]},{"name":"Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingbin","family":"Huang","sequence":"additional","affiliation":[{"name":"Foshan Clinical Medical School of Guangzhou University of Chinese Medicine","place":["Foshan, China"]},{"name":"Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Foshan Clinical Medical School of Guangzhou University of Chinese Medicine","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Garu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Department of Orthopedics, The Second Affiliated Hospital of Zunyi Medical University","place":["Zunyi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xitao","family":"LingHu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Department of Orthopedics, The Second Affiliated Hospital of Zunyi Medical University","place":["Zunyi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchong","family":"Yu","sequence":"additional","affiliation":[{"name":"Foshan Clinical Medical School of Guangzhou University of Chinese Medicine","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangquan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Department of Orthopedics, The Second Affiliated Hospital of Zunyi Medical University","place":["Zunyi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"The Second Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tian","sequence":"additional","affiliation":[{"name":"Foshan Clinical Medical School of Guangzhou University of Chinese Medicine","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Huang","sequence":"additional","affiliation":[{"name":"The First People\u2019s Hospital of Foshan, Foshan Hospital Affiliated to Southern University of Science and Technology","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Foshan Clinical Medical School of Guangzhou University of Chinese Medicine","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"163. e7","DOI":"10.1016\/j.urolonc.2014.11.018","article-title":"Natural history of surgically treated high-risk prostate cancer[C]\/\/Urologic oncology: seminars and original investigations","volume":"33","author":"Briganti","year":"2015","journal-title":"Elsevier"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1038\/s41416-021-01329-6","article-title":"Bone marrow niches in the regulation of bone metastasis","volume":"124","author":"Chen","year":"2021","journal-title":"Br. 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