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>