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. 2020 Jul 12;12(7):1876. doi: 10.3390/cancers12071876

Figure 5.

Figure 5

(A) The inhibition of DNPEP activity potentiates AB737-induced CLL cell death. Mec-1 CLL cells were treated with 300 nM of the BH3-mimetic (ABT737) and with the indicated doses of the developmental DNPEP inhibitor DI93293 for 48 h—after which, the percentage of dead cells was determined with the annexin V assay. * p < 0.05. (B) The potentiating effect of DNPEP inhibition is retained in a microenvironment-modeling culture of CLL. Mec-1 cells were seeded on a monolayer of CD40L-expressing bone marrow stromal cells for 24 h before exposing them to 300-nM ABT737 and indicated doses of the DNPEP inhibitor DI93293 for 48 h. Cell deaths induced were determined with the annexin V assay. The tables under the graphs of parts (A,B) list the combination indices calculated using the Chou-Talalay method (Compusyn). (C–E) The potentiating effect with DNPEP inhibition on primary CLL cells was tested on ABT737 (ABT), the PI3K inhibitor (idelalisib. Idl), and the BTK inhibitor (ibrutinib, Ibt). Mononuclear cells isolated from 5 patients were cultured with bone marrow mesenchymal stromal cell support for 24 h before exposing the cultures to DI93293 alone or in combination with the above drugs for 48 h. The induction of cell death was measured with To-Pro3 staining in the CLL cell population. p-values: * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.