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Targeting sensitive and multidrug resistant leukemia cells with a novel benzofuran-isatin conjugate

Benzofuran-isatin conjugates are considered as promising compounds in cancer prevention and treatment. However, it is not known yet whether these compounds are useful to effectively treat multidrug-resistant tumors. In this study, we investigated the activity of G-5e, a novel benzofuran-isatin conju...

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Main Authors: Jin, Chunmei (Author) , Emam, Mahmoud (Author) , Klauck, Sabine (Author) , Ali, Nadeen T. (Author) , Salem, Rofaida (Author) , Eldehna, Wagdy M. (Author) , Efferth, Thomas (Author) , Hegazy, Mohamed-Elamir F. (Author) , Dawood, Mona (Author)
Format: Article (Journal)
Language:English
Published: 22 March 2025
In: European journal of pharmacology
Year: 2025, Volume: 997, Pages: 1-14
ISSN:1879-0712
DOI:10.1016/j.ejphar.2025.177538
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ejphar.2025.177538
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0014299925002924
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Author Notes:Chunmei Jin, Mahmoud Emam, Sabine M. Klauck, Nadeen T. Ali, Rofaida Salem, Wagdy M. Eldehna, Thomas Efferth, Mohamed-Elamir F. Hegazy, Mona Dawood
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Summary:Benzofuran-isatin conjugates are considered as promising compounds in cancer prevention and treatment. However, it is not known yet whether these compounds are useful to effectively treat multidrug-resistant tumors. In this study, we investigated the activity of G-5e, a novel benzofuran-isatin conjugate in a panel of cell lines exhibiting well-known drug resistance mechanisms (P-gp, BCRP, TP53, EGFR). P-glycoprotein overexpressing CEM/ADR5000 cell line displayed notable hypersensitivity (collateral sensitivity) to G-5e, which was mediated through autophagic cell death activation including downregulation of the autophagy suppressor RND2, upregulation of the autophagy inducer LC3B, and G0/G1 phase arrest during cell cycle progression. Independent of collateral sensitivity, transcriptomic analyses also revealed that G-5e caused downregulation of NF-κB and ERK1/2 pathways. Our findings highlight the potential of benzofuran-isatin conjugates to combat multidrug resistance and the role of RND2 for collateral sensitivity.
Item Description:Online verfügbar: 22 März 2025
Gesehen am 20.04.2026
Physical Description:Online Resource
ISSN:1879-0712
DOI:10.1016/j.ejphar.2025.177538

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