10.1371/journal.pone.0190682.g003 Martin Grundy Martin Grundy Claire Seedhouse Claire Seedhouse Thomas Jones Thomas Jones Liban Elmi Liban Elmi Michael Hall Michael Hall Adam Graham Adam Graham Nigel Russell Nigel Russell Monica Pallis Monica Pallis Co-operative induction of apoptosis by ABT-199 with pladienolide B or torin1. Public Library of Science 2018 drugs sensitising pro-apoptotic anti-leukaemic drug combinations BH 3-only apoptosis agonists BAD MCL -1-targeting MS 1-BH peptide etoposide BAD-BH 3-mediated mitochondrial NOXA target BCL -2 anti-leukaemic drugs sensitising AC 220 BCL -2-targeting BAD-BH 3 peptide 4 hours membrane permeabilisation agents sensitised cells BH 3 BCL -2 DNA inhibitors pladienolide B FLT 3 inhibitor AC 220 cytochrome C release pladienolide B compounds ABT -199 BCL -2 inhibitors ABT -199 BET domain inhibitor JQ 1 downregulate BCL -2 BCL -2 antagonism 2018-01-03 18:39:24 Figure https://plos.figshare.com/articles/figure/Co-operative_induction_of_apoptosis_by_ABT-199_with_pladienolide_B_or_torin1_/5755176 <p><b>(A)</b> MCL-1 long form (L) and short form (S) transcripts (i) and protein (ii) were quantified in untreated cells and cells treated with 10 nM pladienolide B (PLB) for 4 hours. <b>(B)</b> 4E-BP1 phosphorylation (i) and MCL-1 protein (ii) were quantified in untreated cells and cells treated with 1μM torin1 for 4 hours. (<b>C, D)</b> Cells were incubated with 10 nM ABT-199 (199, turquoise), 10 nM pladienolide B (PLB, red), 1 μM torin1 (green) or the indicated combinations (bright blue bar, height = effect with both agents in combination–sum of effects with agents individually). <b>(C)</b> After 4 hours cells were fixed and processed for Cytochrome C release. <b>(D)</b> After 4 hours DiOC6 was added for a further 75 minutes and 7-amino actinomycin D for the last 30 minutes. (Mean+/- SD for n = 3). Fold excess additivism (FEA) is shown on the figures and was calculated as a ratio of observed to expected values after corrections according to the Bliss algorithm (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190682#sec002" target="_blank">methods</a>). Asterisks indicate observed values significantly higher than expected values (P<0.05).</p>