In MV4.11 AML cells, ABT-199 combined with pladienolide B or torin1 enhanced early apoptotic responses beyond Bliss-expected effects. These are combination results from one cell line; the authors reported that dynamic profiling did not predict synergy in 48-hour dose-response assays. [2]
Response is model dependent: 1 μM ABT-199 induced no more than 26% cell death in any of six tested patient-derived glioblastoma stem-like cell lines over the reported 24–48-hour assay interval. [3]
Mitochondrial BCL-2 dependence and AML cell sensitivity
Cell-based study · Panel of 12 human AML cell lines; digitonin-permeabilized cells for JC-1 BH3 profiling and intact cells for viability IC50. [1]
Mitochondrial response to ABT-199 correlated with intact-cell sensitivity. BAD alone did not significantly correlate with ABT-199 IC50 across the full panel; subtracting the BCL-XL-selective HRK response improved specificity. This supports BCL-2-dependent activity without establishing universal AML sensitivity.
Literature-Reported Treatment Conditions
- Treatment concentration
- ABT-199 0.1 μM in mitochondrial profiling; BAD and HRK peptides each 80 μM. Intact-cell ABT-199 was titrated for IC50.
- Exposure duration
- 48 h for intact-cell viability; profiling duration not specified in the reviewed cell-line profiling method.
- Method
- JC-1 mitochondrial membrane-potential loss; intact-cell Annexin V−/PI− viable counts by flow cytometry and Calcusyn IC50 fitting.
- Reported limits
- Profiling vehicle and exact exposure interval not specified in the reviewed cell-line methods; no purified-protein binding Ki extracted.
Methods and source locations
Compound reported in the paper: ABT-199 (venetoclax); Compound label in the paper: ABT-199
Research results for the reported material and model; no claim of validation of an Adooq lot.
Fig. 3B,D,F; Fig. 1A; Results: ABT-199 Operates Selectively on BCL-2 Dependent Mitochondria; Methods: BH3 Profiling of Cell Lines and Treatment of AML Cell Lines
Mitochondrial depolarization by ABT-199 versus intact-cell ABT-199 IC50: JC-1 BH3 profiling; one-tailed Spearman correlation across 12 cell lines. — Fig. 3B and caption
BAD-induced depolarization versus ABT-199 IC50: BAD peptide response; one-tailed Spearman test. — Fig. 3D and caption
BAD minus HRK depolarization response versus ABT-199 IC50: Differential BAD-HRK mitochondrial response; one-tailed Spearman test. — Fig. 3F and caption
Early apoptotic co-operation with pladienolide B or torin1
Cell-based study · Human MV4.11 AML cells. [2]
ABT-199 combined with pladienolide B or torin1 produced supra-additive early cytochrome c release and apoptosis versus the single agents. Pladienolide B plus torin1 did not show comparable co-operation. The authors could not predict synergy in 48-hour dose-response assays with the dynamic profiling assay (data not shown).
Literature-Reported Treatment Conditions
- Treatment concentration
- ABT-199 10 nM; pladienolide B 10 nM; torin1 1 μM; tested individually and in the indicated pairs.
- Exposure duration
- 4 h for cytochrome c release; for apoptosis, DiOC6 added after 4 h for another 75 min, with 7-AAD during the last 30 min.
- Method
- Flow cytometry; combination effects assessed against Bliss expected response.
- Co-treatment
- ABT-199 + pladienolide B or ABT-199 + torin1. Single agents and pladienolide B + torin1 as comparisons.
- Reported limits
- Solvent/vehicle concentration not specified in reviewed Materials and methods.
Methods and source locations
Compound reported in the paper: ABT-199 (venetoclax); Compound label in the paper: ABT-199
Research results for the reported material and model; no claim of validation of an Adooq lot.
Fig. 3A-D; Results section 3; Materials and methods: Materials, Cells, Determination of apoptosis, Bliss calculation; Discussion
Cytochrome c release in ABT-199 combinations: Observed/Bliss-expected response; Fig. 3C: mean ± SD, n = 3. Both ABT-199 combinations marked P < 0.05 versus expected values. — Fig. 3C and caption; Methods Bliss paragraph
Apoptotic response by membrane-potential loss/7-AAD assay: DiOC6 and 7-AAD flow cytometry; mean ± SD, n = 3. Torin1 combination is marked significant; pladienolide B combination is not marked significant in panel D. — Fig. 3D and caption
Limited single-agent response in glioblastoma stem-like cells
Cell-based study · Six patient-derived IDH-wild-type glioblastoma stem-like cell lines (E2, G1, G7, R9, R15, R24); U87MG comparator. [3]
At 1 μM, ABT-199 induced no more than 26% cell death in any tested patient-derived GSC line. BCL-xL- or MCL-1-targeting comparators showed stronger activity in subsets; E2 resisted all tested single agents.
Literature-Reported Treatment Conditions
- Treatment concentration
- ABT-199 1 μM; A-1331852 1 μM and S63845 1 μM as separate comparator treatments.
- Exposure duration
- 24–48 h as reported for the panel; per-line timing not assigned.
- Method
- IncuCyte live cell imaging with SYTOX Green; maximal death control: 1 μM actinomycin D, 10 μM ABT-737 and 1 μM S63845.
- Co-treatment
- Single-agent ABT-199; three-drug mixture used only as maximal cell-death normalization control.
- Reported limits
- Fig. 1 does not specify the solvent control or exact endpoint time for each line.
Methods and source locations
Compound reported in the paper: ABT-199 (venetoclax); Compound label in the paper: ABT-199
Research results for the reported material and model; no claim of validation of an Adooq lot.
Fig. 1A-B; first Results subsection; Methods: Cell culture, Cell proliferation and live cell viability assay
Cell death in patient-derived GSC after ABT-199: IncuCyte/SYTOX Green exclusion, normalized to maximal cell-death control; n = 3 independent experiments per cell line. Bound stated in Results; no individual values inferred from heatmap. — First Results subsection; Fig. 1B and caption
