TY  - JOUR
AU  - Jin, Chunmei
AU  - Emam, Mahmoud
AU  - Klauck, Sabine M
AU  - Ali, Nadeen T
AU  - Salem, Rofaida
AU  - Eldehna, Wagdy M
AU  - Efferth, Thomas
AU  - Hegazy, Mohamed-Elamir F
AU  - Dawood, Mona
TI  - Targeting sensitive and multidrug resistant leukemia cells with a novel benzofuran-isatin conjugate.
JO  - European journal of pharmacology
VL  - 997
SN  - 0014-2999
CY  - New York, NY [u.a.]
PB  - Elsevier
M1  - DKFZ-2025-00612
SP  - 177538
PY  - 2025
N1  - 2025 Mar 22:997:177538
AB  - 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.
KW  - Autophagic cell death (Other)
KW  - Benzofuran-isatin conjugate (Other)
KW  - Collateral sensitivity (Other)
KW  - Multidrug resistance (Other)
KW  - P-glycoprotein (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40122501
DO  - DOI:10.1016/j.ejphar.2025.177538
UR  - https://inrepo02.dkfz.de/record/300114
ER  -