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Natural compounds, including quassinoids such as bruceantin and brusatol, derived from\n                    <jats:italic>Brucea javanica<\/jats:italic>\n                    (L.) Merr., have demonstrated potential as novel cancer chemopreventive agents. Bruceantin exhibits cytotoxic effects against diverse cancer cell lines, including leukemia, lymphoma, and myeloma, primarily through inhibition of protein synthesis and induction of apoptosis via caspase and mitochondrial pathways. Similarly, brusatol has shown broad\u2010spectrum anticancer activities by modulating cellular processes such as apoptosis, cell\u2010cycle arrest, autophagy, and attenuation of epithelial\u2013mesenchymal transition. Mechanistically, it targets key oncogenic signaling pathways, including PI3K\/AKT\/mTOR and Keap1\/NRF2, and enhances chemosensitivity and radiosensitivity. This review evaluates preclinical findings on the pharmacological properties, mechanisms of action, and anticancer efficacy of bruceantin and brusatol. Their structural modifications, safety profiles, and challenges such as poor bioavailability and systemic toxicity are also explored. Advances in semi\u2010synthetic derivatives and drug delivery systems are discussed as strategies to enhance therapeutic potential. Comprehensive insights are provided into the molecular and cellular mechanisms underlying their anticancer effects, supported by in vitro and in vivo evidence. Collectively, these findings highlight the promise of bruceantin and brusatol as therapeutic agents and underscore the need for further translational research to optimize their clinical utility. These quassinoids represent a compelling avenue for the development of targeted and adjunctive cancer therapies, potentially overcoming limitations of conventional treatments.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70142","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T05:54:49Z","timestamp":1764309289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bruceantin and Brusatol: Molecular Insights and Therapeutic Promise of Quassinoids in Cancer Drug Discovery"],"prefix":"10.1002","volume":"358","author":[{"given":"Shumaila","family":"Ijaz","sequence":"first","affiliation":[{"name":"Department of Burn and Plastic Surgery Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9032-2622","authenticated-orcid":false,"given":"Javed","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Botany Bacha Khan University, Charsadda Khyber Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banzeer Ahsan","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Department of Botany Rawalpindi Women University Rawalpindi Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farishta","family":"Zarshan","sequence":"additional","affiliation":[{"name":"Department of Botany Bacha Khan University, Charsadda Khyber Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tabassum","family":"Yaseen","sequence":"additional","affiliation":[{"name":"Department of Botany Bacha Khan University, Charsadda Khyber Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-5753","authenticated-orcid":false,"given":"Zakir","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Plant Sciences, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siraj","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Plant Sciences, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sobia","family":"Kanwal","sequence":"additional","affiliation":[{"name":"Department of Biology and Environmental Sciences Allama Iqbal Open University Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Department of Plant Sciences, Faculty of Biological Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-9116","authenticated-orcid":false,"given":"Daniela","family":"Calina","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Medicine and Pharmacy of Craiova Craiova Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"issue":"1","key":"e_1_2_13_2_1","first-page":"451","article-title":"Global Cancer Statistics 2022: The Trends Projection Analysis","volume":"10","author":"Chhikara B. 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