OIS model | Senolytic | Reference |
---|---|---|
In vitro: H-Ras–induced WI-38 fibroblasts | Navitoclax (ABT-263) | Chang et al., 2016 |
In vitro: KIAA1549:BRAF fusion–driven pilocytic astrocytoma DKFZ-BT66 cells | Navitoclax (ABT-263), ABT-737 | Buhl et al., 2019 |
In vitro: Ras-induced WI-38 fibroblasts | Piperlongumine | Wang et al., 2016 |
In vitro: N-RasG12V–induced murine hepatocytes | Ouabain | Guerrero et al., 2019 |
In vivo: C.B17 SCID/beige mice | Ouabain | Guerrero et al., 2019 |
Ex vivo: β-catenin–positive Hesx1+ embryonic precursor cells | Ouabain, ABT-737 | Guerrero et al., 2019 |
In vitro: Ras-induced IMR90 lung fibroblasts | Navitoclax (ABT-263) | Guerrero et al., 2019 |
In vivo: K-Ras–induced pancreatic premalignant senescence in transgenic mice | ABT-737 | Kolodkin-Gal et al., 2021 |
In vitro: BRAF-V600E–induced BJ human fibroblasts | Ouabain | L’Hôte et al., 2021 |
The table lists examples of senolytics that have been successfully tested in models of OIS both in vitro and in vivo. Despite the limited number of studies, senolytics such as Bcl-2 inhibitors or cardiac glycosides have a promising potential for eliminating oncogene-induced senescent cells accumulating in premalignant lesions. Both ABT-263 and ABT-737 are pan-Bcl-2 inhibitors that interfere with Bcl-2, Bcl-XL, and Bcl-w. Ouabain is a cardiac glycoside that inhibits the Na+/K+-ATPase ion pump. Piperlongumine is a phytochemical that exerts its senolytic activity through inducing oxidative stress in senescent cells.