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000300114 1001_ $$aJin, Chunmei$$b0
000300114 245__ $$aTargeting sensitive and multidrug resistant leukemia cells with a novel benzofuran-isatin conjugate.
000300114 260__ $$aNew York, NY [u.a.]$$bElsevier$$c2025
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000300114 520__ $$aBenzofuran-isatin conjugates are considered as promising compounds in cancer prevention and treatment. However, it is not known yet whether these compounds are useful to effectively treat multidrug-resistant tumors. In this study, we investigated the activity of G-5e, a novel benzofuran-isatin conjugate in a panel of cell lines exhibiting well-known drug resistance mechanisms (P-gp, BCRP, TP53, EGFR). P-glycoprotein overexpressing CEM/ADR5000 cell line displayed notable hypersensitivity (collateral sensitivity) to G-5e, which was mediated through autophagic cell death activation including downregulation of the autophagy suppressor RND2, upregulation of the autophagy inducer LC3B, and G0/G1 phase arrest during cell cycle progression. Independent of collateral sensitivity, transcriptomic analyses also revealed that G-5e caused downregulation of NF-κB and ERK1/2 pathways. Our findings highlight the potential of benzofuran-isatin conjugates to combat multidrug resistance and the role of RND2 for collateral sensitivity.
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000300114 650_7 $$2Other$$aAutophagic cell death
000300114 650_7 $$2Other$$aBenzofuran-isatin conjugate
000300114 650_7 $$2Other$$aCollateral sensitivity
000300114 650_7 $$2Other$$aMultidrug resistance
000300114 650_7 $$2Other$$aP-glycoprotein
000300114 7001_ $$aEmam, Mahmoud$$b1
000300114 7001_ $$0P:(DE-He78)514f8ac681adb9f76d5de4b07ccd143b$$aKlauck, Sabine M$$b2$$udkfz
000300114 7001_ $$aAli, Nadeen T$$b3
000300114 7001_ $$aSalem, Rofaida$$b4
000300114 7001_ $$aEldehna, Wagdy M$$b5
000300114 7001_ $$aEfferth, Thomas$$b6
000300114 7001_ $$aHegazy, Mohamed-Elamir F$$b7
000300114 7001_ $$aDawood, Mona$$b8
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