Fig. 3.

VPA and ATRA show synergistic effects on cell viability and cell death. (A) The combined effect of VPA and ATRA on BE (2)-C (Left) and IMR-32 (Right) cell viability at 5 days, as determined by ATP level, is shown by isobologram. Synergy appears as points below the line of additivity. (B) BE (2)-C cells were treated with compounds for 3 days. Combination treatment induced increased annexin V positive cells consistent with apoptosis with an additive interaction at the low-dose ATRA and synergistic interaction with high-dose ATRA as evaluated by excess over Bliss independence. (C) Western blot analysis of histone acetylation at 6 h in BE (2)-C cells treated with VPA 1 mm (V), ATRA 10 nM (A), and both agents in combination. HeLa cell controls ± butyrate are included.