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Anti-cancer potential of a new derivative of Caffeic Acid Phenethyl Ester targeting the centrosome
Department of Pathology, Medical University of Vienna, Vienna, Austria.
Department of Biological Sciences and Pathobiology, Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.
Department of Biological Sciences and Pathobiology, Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.
Department of Biological Sciences and Pathobiology, Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.
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2025 (Engelska)Ingår i: Redox Biology, E-ISSN 2213-2317, Vol. 81, artikel-id 103582Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds of structure-activity optimization of Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation of genes involved in oxidative stress response and downregulation of DNA replication genes leading to G2/M arrest and subsequent apoptosis induction. In accordance with this, an unbiased proteomics approach, confocal microscopy and molecular modeling showed that TUBGCP2, member of the centrosomal γ-TuRC complex, is a direct interaction partner of CM14. CM14 overcomes ALK inhibitor resistance in ALCL and is also active in T-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia. Interestingly, CM14 also induced cell death in docetaxel-resistant prostate cancer cells thus suggesting an unexpected role in solid cancers. Thus, we synthesized and thoroughly characterized a novel TUBGCP2 targeting drug that is active in ALCL but has also potential for other malignancies.

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Elsevier, 2025. Vol. 81, artikel-id 103582
Nationell ämneskategori
Cell- och molekylärbiologi
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URN: urn:nbn:se:umu:diva-237661DOI: 10.1016/j.redox.2025.103582ISI: 001446494100001PubMedID: 40073758Scopus ID: 2-s2.0-86000586796OAI: oai:DiVA.org:umu-237661DiVA, id: diva2:1954019
Tillgänglig från: 2025-04-23 Skapad: 2025-04-23 Senast uppdaterad: 2025-04-23Bibliografiskt granskad

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