Fig. 4 ALRN-6924 inhibits cellular proliferation and clonogenic capacity, and induces cell cycle arrest and apoptosis in AML cell lines. ALRN-6924 inhibits.

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Fig. 4 ALRN-6924 inhibits cellular proliferation and clonogenic capacity, and induces cell cycle arrest and apoptosis in AML cell lines. ALRN-6924 inhibits cellular proliferation and clonogenic capacity, and induces cell cycle arrest and apoptosis in AML cell lines. (A) Cellular proliferation measured by trypan blue exclusion in AML cell lines 24 hours after treatment with increasing concentrations of ALRN-6924 (n = 3). (B) Time-dependent changes in proliferation in AML cell lines treated with 1 μM ALRN-6924 (n = 3). (C) Fluorescence-activated cell sorting (FACS) analysis of cellular viability, apoptosis, and necrosis measured by annexin V and 4′,6-diamidino-2-phenylindole (DAPI) staining in AML cell lines 24 hours after treatment with increasing concentration of ALRN-6924 (n = 3). (D) Colony-forming capacity (CFC) assay of AML cell lines that were treated with vehicle, 0.5 μM RG7388, or 0.5 μM ALRN-6924 and grown in cytokine-free methylcellulose semisolid medium for 10 days (n = 3). (E) Western blot analysis of p53 in cell lines expressing an empty vector or one of two different p53 short hairpin RNAs (shRNAs) (a representative blot is shown). (F) Cellular proliferation measured by trypan blue exclusion in isogeneic p53 shRNA AML cell lines treated with ALRN-6924 (n = 3). (G) Apoptosis analysis by annexin V and DAPI staining in isogeneic p53 shRNA AML cell lines treated with ALRN-6924 (n = 3). Data are shown as the mean ± SD, and *P < 0.05, **P < 0.01, ***P < 0.001. Luis A. Carvajal et al., Sci Transl Med 2018;10:eaao3003 Published by AAAS