Table 4.
In vitro senolytic effect of tested drugs on different cell lines and different manners of senescence induction.
| Group | Drug | Target | Cell line | Induction | Senolytic | Reference |
|---|---|---|---|---|---|---|
| BH3 mimetics | Navitoclax (ABT-263) | BCL-2, BCL-XL, BCL-W inhibitor | -WI-38 | -Radiation -Replicative exhaustion -Oncogenic RAS expression |
-Yes -Yes -Yes |
(Chang et al., 2016; Zhu et al., 2016; Fuhrmann-Stroissnigg et al., 2017; Pan et al., 2017; Schafer et al., 2017; Grezella et al., 2018) |
| -IMR90 | -Radiation -Etoposide |
-Yes -No |
||||
| -RECs | -Radiation | -Yes | ||||
| -MEFs | -Radiation -Premature aging |
-Yes -Yes |
||||
| -HUVECs | -Radiation | -Yes | ||||
| -Human preadipocytes | -Radiation | -No | ||||
| -Human MSCs | -Replicative exhaustion | -Yes | ||||
| -AECIIs primary pneumocytes (C57BL/6J mice) | -Radiation | -Yes | ||||
| Venetoclax (ABT-199) | BCL-2 inhibitor | -WI-38 | -Radiation | -Yes, in combination with WEHI-539 | (Chang et al., 2016) | |
| -IMR90 | -Etoposide -Oncogenic H-Ras expression |
-No -Yes |
(Yosef et al., 2016) | |||
| ABT-737 | BCL-2, BCL-XL, BCL-W inhibitor | -IMR90 | -Radiation -Etoposide -Oncogenic H-Ras expression -Replicative exhaustion |
-Yes -Yes -Yes -Yes |
(Yosef et al., 2016; Baar et al., 2017) | |
| WEHI-539 | BCL-XL inhibitor | -WI-38 | -Radiation | -Yes in combination with venetoclax | (Chang et al., 2016) | |
| TW-37 | BCL-2, MCL-1 inhibitor | -IMR90 | -Radiation | -Yes | (Zhu et al., 2016) | |
| -HUVECs | -Radiation | -Yes | ||||
| -Human readipocytes | -Radation | -Yes | ||||
| -MEFs | -Oxidative stress -Replicative exhaustion |
-No -No |
||||
| A1331852 | BCL-XL inhibitor | -IMR90 | -Radiation | -Yes | (Zhu et al., 2017) | |
| -HUVECs | -Radiation | -Yes | ||||
| -Human preadipocytes | -Radiation | -No | ||||
| A1155463 | BCL-XL inhibitor | -IMR90 | -Radiation | -Yes | ||
| -HUVECs | -Radiation | -Yes | ||||
| -Human preadipocytes | -Radiation | -No | ||||
| Obatoclax (GX15-070) | BCL-2, BCL-XL, BCL-W inhibitor | -IMR90 | -Etoposide -Oncogenic H-Ras expression |
-No | (Yosef et al., 2016) | |
| FOXO4 inhibitor | FOXO4-DRI | FOXO4-p53 interaction inhibition | -WI-38 | -Radiation | -Yes | (Baar et al., 2017) |
| -IMR90 | -Radiation -Doxorubicin |
-Yes -Yes |
||||
| -BJ | -Radiation | -Yes | ||||
| UBX0101 | UBX0101 | MDM2/p53 | -Primary human chondrocytes | -Osteoarthritis patient | -Yes | (Jeon et al., 2017) |
| Flavenoids and TKI | Quercetin and dasatinib | BCL-2 pathway inhibitor (proteasome activator) PI3K and serpine inhibitor Tyrosine kinase inhibitor (EFNB-dependent suppression of apoptosis) |
-IMR90 | -Radiation -Etoposide |
-Yes/no -Yes |
(Zhu et al., 2015; Baar et al., 2017; Fuhrmann-Stroissnigg et al., 2017; Lehmann et al., 2017; Schafer et al., 2017; Geng et al., 2019; Grezella et al., 2018; Xu et al., 2018) |
| -Pulmonary mouse ATII cells | -Bleomycin | -Yes | ||||
| -HUVECs | -Radiation -Replicative exhaustion |
-Yes -Yes |
||||
| -Human preadipocytes | -Radiation -Replicative exhaustion |
-Yes/no -Yes |
||||
| -MEFs | -Radiation -Premature aging |
-Yes -Yes |
||||
| -MSCs | -Replicative exhaustion -Premature aging |
-No -No |
||||
| Fisetin | BCL-2 pathway inhibitor (hydrophobic groove of BCL-2) | -IMR90 | -Etoposide | -No (decreased senescence, no apoptosis) | (Yousefzadeh et al., 2018) | |
| -HUVECs | -Etoposide | -Yes | ||||
| -MEFs | -Etoposide -Premature aging |
-No -No |
||||
| -MSCs | -Replicative exhaustion | -No | (Zhu et al., 2017) | |||
| HSP90 inhibitors | 17-DMAG | Inhibits the molecular chaperone HSP90, leading to AKT and ERK destabilization | -WI-38 | -Replicative exhaustion | -Yes | (Fuhrmann-Stroissnigg et al., 2017) |
| -IMR90 | -Etoposide | -Yes | ||||
| -MEFs | -Premature aging | -Yes | ||||
| -MSC | -Oxidative stress | -Yes | ||||
| Geldanamycin | -MEFs | -Premature aging | -Yes | |||
| Niacine | Nicotinamide riboside | Nicotinamide adenine dinucleotide (NAD+) increase | -MSCs | -Replicative exhaustion | -No | (Grezella et al., 2018) |
| Resveralogues | Resveratrol | Activation of SIRT1 (NAD-dependent protein deacetylase) | -NHDF (human fibroblasts) | -Replicative exhaustion | -No | (Latorre et al., 2017) |
| -HF043 (human dermal fibroblasts) | -Replicative exhaustion | -No | ||||
| -MRC5 (human lung fibroblasts) | -Replicative exhaustion | -No |
Senolytic effect is defined as a selective induction of apoptosis in senescent cells. Cell lines: WI-38, human lung fibroblasts; IMR90, human lung fibroblasts; RECs, human renal epithelial cells; HUVECs, human umbilical vein endothelial cells; BJ, human foreskin fibroblasts; MSC (femoral bone marrow); NHDFs, normal human dermal fibroblasts.