Fig. 4. Astemizole initiates apoptosis in the G0/G1 cell cycle phase independently of the H1 receptor.

a Viability of AML 8227 cells treated with the H1-antihistamines cetirizine, fexofenadine and diphenhydramine up to 50 μM for 6 days. b Viability of AML 8227 after the addition of 10 μM histamine to 10 μM astemizole or 4 μM terfenadine treatment for 4 days. c Enrichment map of CMap expression data revealing astemizole modulated pathways. Nodes (circles) represent gene sets and edges (lines) represent shared genes. d GSEA plot of negative enrichment of cell cycle and G1/S transition using the gene expression signature of cells treated with astemizole from CMap. e Apo-BrdU TUNEL assay on MOLM-13 cells treated with 10 μM astemizole for 24 h. f Cell cycle analysis using Ki-67 on MOLM-13 and 8227 cells with 10 μM astemizole for 24 h. g Viability of MOLM-13 cell growth in serum-starved (0% FBS) or normal conditions (20% FBS) after 24 h of treatment with indicated doses of astemizole. Data are representative of at least two independent experiments performed in triplicate and represent the mean ± s.d.; **p ≤ 0.01, ***p ≤ 0.001