AR420626 elicits an extrinsic apoptotic pathway and histone deacetylase inhibition. (a, b) HepG2 and HLE cells were treated with vehicle or AR420626 (10, 25 µM) for 48 h. Western blotting was used to detect histone H3 acetylation and the apoptosis-related proteins, cleaved caspase-3, -8, and -9, in cell lysates. Levels of cleaved caspase-3, -8, and -9 and acetyl-H3 (all relative to β-actin) were set to 1.0 in cells treated with vehicle. Data are shown as the mean ± SD of 3 separate experiments. *p < 0.05, **p < 0.01, NS: not significant by one-way analysis of variance with a Tukey–Kramer multiple comparison test. (c) HepG2 and HLE cells were treated with AR420626 (25 µM) for 1, 3, 12, and 24 h. Western blotting was used to detect histone H3 acetylation and cleaved caspase-3 and -8 in cell lysates. (d) Immunoblotting of GPR41 in cells with small interfering RNA (siRNA)-mediated GPR41 knockdown for 48 h. (e) HepG2 cells treated with control or GPR41 siRNA were treated with vehicle or AR420626 (25 µM). Western blotting was used to detect histone H3 acetylation and cleaved caspase-3 in cell lysates.