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@ARTICLE{Jin:300114,
author = {C. Jin and M. Emam and S. M. Klauck$^*$ and N. T. Ali and
R. Salem and W. M. Eldehna and T. Efferth and M. F. Hegazy
and M. Dawood},
title = {{T}argeting sensitive and multidrug resistant leukemia
cells with a novel benzofuran-isatin conjugate.},
journal = {European journal of pharmacology},
volume = {997},
issn = {0014-2999},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2025-00612},
pages = {177538},
year = {2025},
note = {2025 Mar 22:997:177538},
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.},
keywords = {Autophagic cell death (Other) / Benzofuran-isatin conjugate
(Other) / Collateral sensitivity (Other) / Multidrug
resistance (Other) / P-glycoprotein (Other)},
cin = {B063},
ddc = {610},
cid = {I:(DE-He78)B063-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40122501},
doi = {10.1016/j.ejphar.2025.177538},
url = {https://inrepo02.dkfz.de/record/300114},
}