Figure 5.

Flavopiridol-mediated downregulation of MCL-1 sensitizes BCL2^High NHL cell lines to navitoclax and venetoclax in a caspase-dependent manner. BCL2^High NHL cell lines were co-treated with navitoclax (1 μM) or venetoclax (1 μM) in combination with flavopiridol at 0, 16.67, 50 or 150 nM (a) or 50 nM (b) for 24 h before assessing effects on MCL-1, BCL-2, caspase-3, PARP and β-actin by western blot. Alternatively BCL2^High cell lines were pre-treated with z-VAD-fmk (50 μM) for 1 h and then co-treated with navitoclax (1 μM) or venetoclax (1 μM) in combination with A-1210477 (5 μM) or flavopiridol (50 nM) for a further 24 h and the effect on apoptosis determined by flow cytometric analysis of Annexin-V/7-AAD staining. Representative flow cytometry histograms in SU-DHL-4 cells from three independent experiments are shown in c and quantified in d.