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- W3042084711 abstract "1800 We previously reported that ABT-737, a BH3-mimetic, synergistically increased cytotoxcity in combination with 4-HPR, a cytotoxic retinoid in acute lymphobastic leukemia (ALL) cell lines (Proc AACR, abstract #1336, 2006). We further investigated the mechanism of synergy and the differential cytotoxicity between leukemia cells and normal cells of ABT-737 + 4-HPR. Cytotoxicity was determined using a fluorescence-based digital imaging assay (DIMSCAN). Changes in Bcl-2 family proteins were detected by immunoblotting. Reactive oxygen species (ROS) generation (DCFDA fluorescence) and phospho-Jun kinase (p-JNK) were measured by flow cytometry. ABT-737 increased Mcl-1 protein only in ABT-737-resistant ALL cell lines, while 4-HPR inactivated Mcl-1 via reactive oxygen species (ROS) generation and JNK phosphorylation. In CEM cells the antioxidant ascorbic acid (AA), completely abrogated ROS generation (43.5 ± 2.67-fold increase by 10 μM 4-HPR alone versus 0.75 ± 0.07-fold increase by AA + 4-HPR relative to untreated control), JNK phosphorylation and Mcl-1 inactivation, and attenuated the cytotoxicity of 4-HPR (p" @default.
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- W3042084711 date "2007-05-01" @default.
- W3042084711 modified "2023-09-23" @default.
- W3042084711 title "Fenretinide inactivation of Mcl-1 enhanced activity of the Bcl-2 family inhibitor ABT-737 in acute lymphoblastic leukemia cell lines" @default.
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