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| Home > Publications database > Targeting sensitive and multidrug resistant leukemia cells with a novel benzofuran-isatin conjugate. |
| Home > Publications database > Targeting sensitive and multidrug resistant leukemia cells with a novel benzofuran-isatin conjugate. |
| Journal Article | DKFZ-2025-00612 |
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2025
Elsevier
New York, NY [u.a.]
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Please use a persistent id in citations: doi:10.1016/j.ejphar.2025.177538
Abstract: 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.
Keyword(s): Autophagic cell death ; Benzofuran-isatin conjugate ; Collateral sensitivity ; Multidrug resistance ; P-glycoprotein
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