{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:26:00Z","timestamp":1786951560302,"version":"build-2736575974"},"reference-count":105,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Goniothalamin (GTN), a natural styryl\u2010lactone from the\n                    <jats:italic>Goniothalamus<\/jats:italic>\n                    genus, has demonstrated cytotoxic properties against a variety of human cancer cell lines with minimal effects on normal cells. Its traditional medicinal use and preliminary preclinical evidence suggest potential as a selective anticancer agent. The purpose of this review is to summarize the preclinical anticancer activity, molecular mechanisms, and therapeutic potential of GTN and its semi\u2010synthetic derivatives across cancer cell lines and animal models. A comprehensive literature search was conducted on the anticancer effects of GTN using databases including PubMed, Scopus, and ScienceDirect. Studies reporting\n                    <jats:italic>in\u2010vitro<\/jats:italic>\n                    cytotoxicity, half\u2010maximal inhibitory concentration (IC50) values, mechanisms of action, synergistic drug effects, and in\u2010vivo antitumor efficacy were included. Data on GTN enantiomers and semisynthetic derivatives were also analyzed. GTN exhibited potent, dose\u2010 and time\u2010dependent cytotoxicity in breast, colorectal, hepatoma, leukemia, and other cancer cell lines (IC\n                    <jats:sub>50<\/jats:sub>\n                    in the low micromolar range), while sparing normal cells. Mechanistically, GTN induced DNA damage, reactive oxygen species (ROS) generation, cell cycle arrest, endoplasmic reticulum stress, apoptosis, autophagy, necroptosis, and anoikis. The anticancer activity of GTN enantiomers appears to be cell\u2010line dependent: although the (R)\u2010enantiomer showed higher potency in several cancer models, the (S)\u2010enantiomer displayed greater activity in selected cancer cell lines. GTN synergized with chemotherapeutics such as paclitaxel, vinblastine, and cisplatin, enhancing apoptosis and reducing cell viability. Semi\u2010synthetic derivatives, including methoxy\u2010 and nitro\u2010substituted analogs, demonstrated enhanced potency and selectivity. In animal models, GTN exhibited antitumor activity without detectable toxicity. GTN is a promising natural anticancer agent with multimodal mechanisms of action and selective cytotoxicity. Semisynthetic derivatives further improve its potency and specificity. Further in\u2010vivo studies, bioavailability, and pharmacokinetic investigations are warranted to advance GTN towards clinical application.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71040","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:55:21Z","timestamp":1785142521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Goniothalamin as a Styryl\u2010Lactone Toxicophore in Cancer Models: Electrophile\u2010Driven DNA Damage, Reactive Oxygen Species\u2013Endoplasmic Reticulum Stress Signaling and Detoxification\u2010Relevant Safety Considerations"],"prefix":"10.1002","volume":"40","author":[{"given":"Nata\u0161a","family":"Jokovi\u0107","sequence":"first","affiliation":[{"name":"Department of Biology and Ecology, Faculty of Science and Mathematics University of Ni\u0161 Ni\u0161 Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Strahinja","family":"Pe\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Biology and Ecology, Faculty of Science and Mathematics University of Ni\u0161 Ni\u0161 Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Novakovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Biology and Ecology, Faculty of Science and Mathematics University of Ni\u0161 Ni\u0161 Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u0111ela Dubroja","family":"Krsti\u0107","sequence":"additional","affiliation":[{"name":"Department of Biology and Ecology, Faculty of Science and Mathematics University of Ni\u0161 Ni\u0161 Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-23-0411"},{"key":"e_1_2_10_3_1","volume-title":"Global Cancer Observatory: Cancer Today (Vol. 20182020)","author":"Ferlay J.","year":"2020"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5742(02)00046-7"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/life12010048"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01302-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.842376"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16101878"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12010201"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.18639\/RABM.2016.02.292264"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2006.05.010"},{"key":"e_1_2_10_12_1","first-page":"140","article-title":"Antimalarial Properties of Goniothalamin in Combination With Chloroquine Against Plasmodium Yoeliiand Plasmodium Berghei Growth in Mice","volume":"23","author":"MOHD Ridzuan M. 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