Fig. 2: Pharmacological inhibition of TrkB selectively induces apoptotic death of senescent cells.
From: A BDNF-TrkB autocrine loop enhances senescent cell viability
a Viability curves obtained after testing a range of concentrations of Trk inhibitor drugs (GNF 5837, ANA 12, PF 06273340) for 48 h in WI-38 fibroblasts that were either proliferating or undergoing etoposide-induced senescence (ETIS). b Representative micrographs of select doses for each drug tested in (a); bar, 100 µm. Cell viability (c) and caspase 3/7 activity (d) were assessed 48 h after the indicated treatments and doses in WI-38, BJ, IMR-90, HSAEC, HREC, and HUVEC cultures undergoing ETIS, and WI-38 cultures undergoing oxidative stress-induced senescence (OSIS), ionizing radiation-induced senescence (IRIS), and replicative senescence (RS). Assessments of cell viability (e) and caspase 3/7 activity (f) measured in WI-38 cells undergoing ETIS that were treated for 48 h with different Trk inhibitors, either alone or in combination with the pan-caspase inhibitor Z-VAD-FMK at the indicated doses. Graphs in a, c–f, represent the mean values ± SD of n = 3 experiments; significance (*p < 0.05, **p < 0.01, ***p < 0.001) was determined by using two-tailed Student’s t-test.
