Goniothalamin as a Styryl-Lactone Toxicophore in Cancer Models: Electrophile-Driven DNA Damage, Reactive Oxygen Species-Endoplasmic Reticulum Stress Signaling and Detoxification-Relevant Safety Considerations.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Goniothalamin as a Styryl-Lactone Toxicophore in Cancer Models: Electrophile-Driven DNA Damage, Reactive Oxygen Species-Endoplasmic Reticulum Stress Signaling and Detoxification-Relevant Safety Considerations.
Συγγραφείς:	Joković N; Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Niš, Serbia., Pešić S; Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Niš, Serbia., Novaković M; Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Niš, Serbia., Krstić AD; Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš, Niš, Serbia., Setzer WN; Aromatic Plant Research Center, Lehi, Utah, USA.; Department of Chemistry, University of Alabama in Huntsville, Huntsville, Alabama, USA., Sharifi-Rad J; Universidad Espíritu Santo, Samborondón, Ecuador.; Department of Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.; Centro de Estudios Tecnológicos y Universitarios del Golfo, Veracruz, Mexico., Calina D; Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
Πηγή:	Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2026 Aug; Vol. 40 (8), pp. e71040.
Τύπος έκδοσης:	Journal Article; Review
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Wiley Country of Publication: United States NLM ID: 9717231 Publication Model: Print Cited Medium: Internet ISSN: 1099-0461 (Electronic) Linking ISSN: 10956670 NLM ISO Abbreviation: J Biochem Mol Toxicol Subsets: MEDLINE
Imprint Name(s):	Original Publication: New York, NY : Wiley, c1998-
Ιατρικοί όροι (MeSH):	Pyrones/chemistry , Pyrones/pharmacology , Pyrones/therapeutic use , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology, Antineoplastic Agents/pharmacology ; Endoplasmic Reticulum Stress/drug effects ; Reactive Oxygen Species/metabolism ; DNA Damage/drug effects ; Signal Transduction/drug effects ; Humans
Περίληψη:	Goniothalamin (GTN), a natural styryl-lactone from the Goniothalamus 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-synthetic 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 in-vitro cytotoxicity, half-maximal inhibitory concentration (IC50) values, mechanisms of action, synergistic drug effects, and in-vivo antitumor efficacy were included. Data on GTN enantiomers and semisynthetic derivatives were also analyzed. GTN exhibited potent, dose- and time-dependent cytotoxicity in breast, colorectal, hepatoma, leukemia, and other cancer cell lines (IC50 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-line dependent: although the (R)-enantiomer showed higher potency in several cancer models, the (S)-enantiomer 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-synthetic derivatives, including methoxy- and nitro-substituted 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-vivo studies, bioavailability, and pharmacokinetic investigations are warranted to advance GTN towards clinical application. (© 2026 The Author(s). Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC.)
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Contributed Indexing:	Keywords: DNA damage; autophagy; cancer cell lines; chemotherapeutic synergy; goniothalamin; natural product; styryl‐lactone
Substance Nomenclature:	34W9GO6B2Z (goniothalamin) 0 (Pyrones) 0 (Antineoplastic Agents) 0 (Reactive Oxygen Species)
Entry Date(s):	Date Created: 20260727 Date Completed: 20260925 Latest Revision: 20260925
Update Code:	20260926
PubMed Central ID:	PMC13403094
DOI:	10.1002/jbt.71040
PMID:	42504622
Βάση Δεδομένων:	MEDLINE

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