Research Paper Volume 9, Issue 3 pp 955—963

New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463

Figure 3. A1155463 targets senescent cells. (a) Structure of A1155463. (b-d) A1155463 is more effective in reducing viability (ATPLite) of senescent HUVECs and IMR90 cells than primary human preadipocytes. Proliferating or senescent cells were exposed to different concentrations of A1155463 for 3 days. The red lines denote ATPLite intensities on day 0 of senescent and non-senescent cells, both set to 100%. HUVEC and IMR90 data are means±SEM of 5 replicates at each drug concentration. Preadipocyte data are means±SEM of 5 replicates from each of 4 different subjects at each concentration. (e-g) A1155463 selectively reduces senescent but not proliferating HUVECs and IMR90 cell numbers (crystal violet). The red lines denote cell numbers at plating on day 0 of senescent and non-senescent cells, both set to 100%. HUVEC and IMR90 data are means±SEM of 5 replicates at each drug concentration. Preadipocyte data are means±SEM of 5 replicates from each of 4 different subjects at each concentration. (h-i) A1155463 induces apoptosis in senescent HUVECs and IMR90 cells. HUVECs were treated with A1155463 for 12h and then caspases-3&7 were assayed using a luminescent substrate. A1155463 (1 nM) induced apoptosis in senescent cells by caspase 3/7 activity assay.