SK053 An Inhibitor Of Enzymes Involved In Allosteric Disulfide Bonds Formation Induces Differentiation Of Human AML Cells by Justyna Chlebowska, Malgorzata.

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SK053 An Inhibitor Of Enzymes Involved In Allosteric Disulfide Bonds Formation Induces Differentiation Of Human AML Cells by Justyna Chlebowska, Malgorzata Firczuk, Karolina Furs, Angelika Muchowicz, Radoslaw Sadowski, Adam D. Staruch, Szymon Klossowski, Ryszard Ostaszewski, Anna Paulina Dabrowska-Iwanicka, Jakub Golab, and Dominika Nowis Blood Volume 122(21):4215-4215 November 15, 2013 ©2013 by American Society of Hematology

SK053 is a potent anti-leukemic agent that induces differentiation of human AML cells. SK053 is a potent anti-leukemic agent that induces differentiation of human AML cells. (A) Cytostatic/cytotoxic activity of SK053 in human AML cell lines evaluated with trypan blue staining, mean percentage of dead cells ± SD, n=6; *P<0.05 vs controls, one-way ANOVA with Dunett’s post test; (B) SK053 inhibits enzymatic activity of recombinant human PDI in a turbidimetric assay of insulin disulfide reduction; 130 µM bacitracin served as a positive control; (C) qPCR results presented as mean target-to-reference ratio ± SD (left) CEBPA expression in HL60 cells incubated for indicated time with 10 µM SK053; (right) HK3 expression in HL60 cells incubated for 48 hours with 10 µM SK053, or 1 µM ATRA (positive control); (D) SK053 increases amount of CEBPA protein in nuclear fraction of HL60 cells incubated for 2 or 5 days with 1 µM ATRA (positive control), 2 mM bacitracin (PDI inhibitor) or 10 µM SK053; the figure presents results of Western blot, HDAC2 served as a marker of nuclear fraction, ß-actin served as a loading control. Malgorzata Firczuk et al. Blood 2013;122:4215 ©2013 by American Society of Hematology