Journal: Scientific Reports

Article Title: Inhibition of MCL1 induces apoptosis in anaplastic large cell lymphoma and in primary effusion lymphoma

doi: 10.1038/s41598-022-04916-6

Figure Lengend Snippet: Expression of BCL2 family genes in the LL-100 panel. ( a ) Heat map of RNA-seq gene expression data of BCL2 family members. Framed in red are expression levels of MCL1 and BCL2 in ALCL and PEL. ( b ) Results of qRT-PCR showing expression of BCL2 family members. ( c ) Western blot analysis showing the protein expression of MCL1, BCL2 and BCLXL in ALCL and PEL cell lines. DLBCL and MM cell lines were included as controls. Note that ALCL and PEL cell lines are consistently MCL1 pos /BCL2 neg .

Article Snippet: Life cell imaging data showing the effect of the MCL1 inhibitor AZD-5991 (300 nM) and the BCL2/BCLXL inhibitor ABT-263 (300 nM) on growth (48 h) and apoptosis (12 h) of ( a ) L-82, SU-DHL-1 and ( b ) SR-786, KARPAS-299. ( c ) shows effects of AZD-5991 and BEZ-235 on growth and apoptosis of cell lines L-82 and SU-DHL-1.

Techniques: Expressing, RNA Sequencing, Gene Expression, Quantitative RT-PCR, Western Blot

Journal: Scientific Reports

Article Title: Inhibition of MCL1 induces apoptosis in anaplastic large cell lymphoma and in primary effusion lymphoma

doi: 10.1038/s41598-022-04916-6

Figure Lengend Snippet: SiRNA-mediated knockdown of BCL2 family members in ALCL cell lines. Life cell imaging shows effects of knockdown of BCL2 family members on growth (cell counts) and apoptosis (caspase 3/7 activity) 48 h after onset of treatment with siRNA oligos. ( a ) Knockdown of MCL1 and BCLXL; ( b ) knockdown of MCL1 and BCL2A1. Note synergistic effects of MCL1 and BCLXL knockdown in cell line L-82 and additive effects of MCL1 and BCL2A1 knockdown in cell line SU-DHL-1. The horizontal line shows the expected additive effects of the combination of siRNA oligos.

Article Snippet: Life cell imaging data showing the effect of the MCL1 inhibitor AZD-5991 (300 nM) and the BCL2/BCLXL inhibitor ABT-263 (300 nM) on growth (48 h) and apoptosis (12 h) of ( a ) L-82, SU-DHL-1 and ( b ) SR-786, KARPAS-299. ( c ) shows effects of AZD-5991 and BEZ-235 on growth and apoptosis of cell lines L-82 and SU-DHL-1.

Techniques: Knockdown, Imaging, Activity Assay

Journal: Scientific Reports

Article Title: Inhibition of MCL1 induces apoptosis in anaplastic large cell lymphoma and in primary effusion lymphoma

doi: 10.1038/s41598-022-04916-6

Figure Lengend Snippet: Effect of AZD-5991 and ABT-263 on growth and apoptosis of ALCL cell lines. Life cell imaging data showing the effect of the MCL1 inhibitor AZD-5991 (300 nM) and the BCL2/BCLXL inhibitor ABT-263 (300 nM) on growth (48 h) and apoptosis (12 h) of ( a ) L-82, SU-DHL-1 and ( b ) SR-786, KARPAS-299. ( c ) shows effects of AZD-5991 and BEZ-235 on growth and apoptosis of cell lines L-82 and SU-DHL-1. Apoptosis was assessed by caspase 3/7 activity. The horizontal line shows the expected additive effects of the combination of both inhibitors. Note that the only cell line that does not respond to ABT-263 is the BCLXL low cell line KARPAS-299.

Article Snippet: Life cell imaging data showing the effect of the MCL1 inhibitor AZD-5991 (300 nM) and the BCL2/BCLXL inhibitor ABT-263 (300 nM) on growth (48 h) and apoptosis (12 h) of ( a ) L-82, SU-DHL-1 and ( b ) SR-786, KARPAS-299. ( c ) shows effects of AZD-5991 and BEZ-235 on growth and apoptosis of cell lines L-82 and SU-DHL-1.

Techniques: Imaging, Activity Assay

Journal: Frontiers in Oncology

Article Title: Co-operation of MCL-1 and BCL-X L anti-apoptotic proteins in stromal protection of MM cells from carfilzomib mediated cytotoxicity

doi: 10.3389/fonc.2024.1394393

Figure Lengend Snippet: Effect of combining BH-3 mimetics with CFZ in MM cells co-cultured with HS5 and cooperativity of anti-apoptotic proteins on resistance to CFZ. (A) 48h co-cultures of MM1.s with HS5 were set up, following treatment with 25nM CFZ. BH-3 mimetics (100nM S63845, 1µM ABT-199, 1nM A-1331852) were added to co-cultures. Data are presented as mean +/- SEM of 3 independent experiments. p<0.05 deemed statistically significant.**** p<0.0001, **p=0.01 (B) The combination of CFZ (25nM) and BH-3 mimetics (10nM) tested on MNCs derived from newly diagnosed MM patients (n=8). The loss of CD138+ MM cells was measured by flow cytometry following staining with CD138 Ab. Note: Patient marked with a pink triangle is missing three data points (not enough cells). (C) MCL-1 IP- Protein lysates from MM1.s were subjected to MCL-1 immunoprecipitation. Protein lysates were prepared 6h post-CFZ and BH-3 mimetics exposure (D, E) BIM IP- Protein lysates from MM1.s were subjected to BIM immunoprecipitation. Protein lysates were prepared 24h post-CFZ and BH-3 mimetics exposure. Line: 1.Ctrl; 2. 25nM CFZ; 3.100nM CFZ; 4.100nM S63845 (MCL-1 inhibitor); 5.1nM A-1331852 (BCL-X L inhibitor); 6.25nM CFZ+ S63845; 7.25nM CFZ+ A-1331852; 8. S63845+ A-1331852.

Article Snippet: The following BH-3 mimetics were used: MCL-1 inhibitors: S63845 (CymanChem), AZD5991 (Stratech Scientific), BCL-X L inhibitor: A-1331852 (Abcam), BCL-2 inhibitor: ABT-199 (Venetoclax; BioVision), BCL-2/BCL-X L dual inhibitor: ABT-263 (Navitoclax; Abcam).

Techniques: Cell Culture, Derivative Assay, Flow Cytometry, Staining, Immunoprecipitation