{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:38:50Z","timestamp":1773005930750,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Brucine (BRU), a naturally occurring indole alkaloid primarily derived from\n                    <jats:italic>Strychnos nux\u2010vomica<\/jats:italic>\n                    , has recently gained attention for its notable anticancer potential. Preclinical studies using both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models have demonstrated that BRU and its semi\u2010synthetic derivatives exhibit significant inhibitory effects on tumor development across various cancer types, including cervical, breast, liver, skin, colon, and prostate cancers. This review explores the phytochemical properties of BRU, its chemical modifications, bioavailability, pharmacokinetics, mechanisms of anticancer activity, as well as findings from clinical research, toxicity profiles, and safety evaluations. Compared to conventional chemotherapeutic agents, BRU offers a promising alternative due to its broad\u2010spectrum efficacy and natural origin, although its therapeutic application is limited by a narrow safety margin. Therefore, future research should focus on the development of optimized semi\u2010synthetic derivatives and advanced drug delivery systems to enhance its pharmacological performance while minimizing toxicity, supporting its potential as a viable candidate in anticancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/cbin.70143","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T06:51:53Z","timestamp":1770101513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brucine as a Natural Modulator of Cancer Signaling: Cellular Mechanisms, Therapeutic Potential, and Translational Perspectives"],"prefix":"10.1002","volume":"50","author":[{"given":"Putri Cahaya","family":"Situmorang","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences Universitas Sumatera Utara Medan Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Helen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara Medan Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2016-0151","authenticated-orcid":false,"given":"Rony Abdi","family":"Syahputra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara Medan Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8849-2481","authenticated-orcid":false,"given":"Sony Eka","family":"Nugraha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Faculty of Pharmacy Universitas Sumatera Utara Medan Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etti Sartina","family":"Siregar","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences Universitas Sumatera Utara Medan Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doni Aldo Samuel","family":"Siahaan","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences Universitas Sumatera Utara Medan Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-2612","authenticated-orcid":false,"given":"Zainab M.","family":"Almarhoon","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science King Saud University Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3639-0528","authenticated-orcid":false,"given":"William N.","family":"Setzer","sequence":"additional","affiliation":[{"name":"Aromatic Plant Research Center Lehi Utah USA"},{"name":"Department of Chemistry University of Alabama in Huntsville Huntsville Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-8151","authenticated-orcid":false,"given":"Javad","family":"Sharifi\u2010Rad","sequence":"additional","affiliation":[{"name":"Universidad Esp\u00edritu Santo Samborond\u00f3n Ecuador"},{"name":"Department of Medicine, College of Medicine Korea University Seoul Republic of Korea"},{"name":"Centro de Estudios Tecnol\u00f3gicos y Universitarios del Golfo Veracruz Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2021.111868"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bab.2719"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-021-02841-5"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/4646855"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16010047"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/6957519"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-1758895"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2024.42.16_suppl.10564"},{"key":"e_1_2_18_10_1","unstructured":"Dassault Syst\u00e8mes BIOVIA.2025. \"BIOVIA Discovery Studio Visualizer. Version 2025\" San Diego (CA): Dassault Syst\u00e8mes.https:\/\/www.3ds.com\/products\/biovia."},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.33371\/ijoc.v17i2.982"},{"key":"e_1_2_18_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2020.1797237"},{"key":"e_1_2_18_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3056802"},{"key":"e_1_2_18_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18040757"},{"key":"e_1_2_18_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/pm.pm_95_20"},{"key":"e_1_2_18_16_1","doi-asserted-by":"publisher","DOI":"10.14233\/ajchem.2013.14674"},{"key":"e_1_2_18_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-024-01348-z"},{"key":"e_1_2_18_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28031341"},{"key":"e_1_2_18_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2024.106159"},{"key":"e_1_2_18_20_1","doi-asserted-by":"publisher","DOI":"10.3923\/pjbs.2022.49.55"},{"key":"e_1_2_18_21_1","doi-asserted-by":"publisher","DOI":"10.4103\/pm.pm_126_22"},{"key":"e_1_2_18_22_1","doi-asserted-by":"publisher","DOI":"10.4103\/pm.pm_126_22"},{"key":"e_1_2_18_23_1","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20231205.401"},{"key":"e_1_2_18_24_1","doi-asserted-by":"crossref","unstructured":"Huang R. J.Jin L.Lu et al.2020. \u201cBrucine: A Review of Phytochemistry Pharmacology and Toxicology.\u201d Frontiers in Pharmacology 11.https:\/\/doi.org\/10.3389\/fphar.2020.00377.","DOI":"10.3389\/fphar.2020.00377"},{"key":"e_1_2_18_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S445206"},{"key":"e_1_2_18_26_1","doi-asserted-by":"publisher","DOI":"10.3923\/pjbs.2022.29.36"},{"key":"e_1_2_18_27_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21858"},{"key":"e_1_2_18_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26113454"},{"key":"e_1_2_18_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phyplu.2023.100490"},{"key":"e_1_2_18_30_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.87514"},{"key":"e_1_2_18_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118200"},{"key":"e_1_2_18_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02246-y"},{"key":"e_1_2_18_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym16101428"},{"key":"e_1_2_18_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2023.104859"},{"key":"e_1_2_18_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115680096274284231116104554"},{"key":"e_1_2_18_36_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.53689"},{"key":"e_1_2_18_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00377"},{"key":"e_1_2_18_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00700-w"},{"key":"e_1_2_18_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16060800"},{"key":"e_1_2_18_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.886433"},{"key":"e_1_2_18_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00104"},{"key":"e_1_2_18_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.136667"},{"key":"e_1_2_18_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.11.013"},{"key":"e_1_2_18_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23304"},{"key":"e_1_2_18_45_1","doi-asserted-by":"publisher","DOI":"10.3897\/pharmacia.70.e96811"},{"key":"e_1_2_18_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/bab.2719"},{"key":"e_1_2_18_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-45741-9"},{"key":"e_1_2_18_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000035101"},{"key":"e_1_2_18_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/gead033"},{"key":"e_1_2_18_50_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0044-1791937"},{"key":"e_1_2_18_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2021.111332"},{"key":"e_1_2_18_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-024-01606-w"},{"key":"e_1_2_18_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28248038"},{"key":"e_1_2_18_54_1","unstructured":"World Health Organization (WHO); International Agency for Research on Cancer (IARC).2024. GLOBOCAN 2022: Indonesia Cancer Fact Sheet. Lyon (FR): International Agency for Research on Cancer; 2024 [cited 2025 Jan 21].https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/populations\/360-indonesia-fact-sheet.pdf."},{"key":"e_1_2_18_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2023.213566"},{"key":"e_1_2_18_56_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S17255"},{"key":"e_1_2_18_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01213-z"},{"key":"e_1_2_18_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000033625"},{"key":"e_1_2_18_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43450-021-00204-y"},{"key":"e_1_2_18_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43450-021-00204-y"},{"key":"e_1_2_18_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joim.2025.03.001"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.70143","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbin.70143","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.70143","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:21:32Z","timestamp":1772997692000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.70143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/cbin.70143"],"URL":"https:\/\/doi.org\/10.1002\/cbin.70143","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70143"}}