Fig. 8: Primary senescent fibroblast and epithelial cells are resistant to PI3K-inhibitor-induced senolysis. | Cell Death & Disease

Fig. 8: Primary senescent fibroblast and epithelial cells are resistant to PI3K-inhibitor-induced senolysis.

From: Combined inhibition of class 1-PI3K-alpha and delta isoforms causes senolysis by inducing p21WAF1/CIP1 proteasomal degradation in senescent cells

Fig. 8

A The immortalized primary fibroblast BJ/hTERT and epithelial RPE-340/hTERT cell lines were exposed to 20 Gy γIR and senescence induction was determined by staining for senescence-associated beta-galactosidase activity at day 4 and day 7 following irradiation. Senescent cells display a strong blue color. Microscopic pictures were taken with the same 10x magnification (scale bar 100 µM in the lower right panel) and are representative of at least three independent experiments. B Western blot analyses of the expression of the indicated proteins in BJ/hTERT and RPE-340/hTERT cells at one, three and seven days after 20 Gy γIR. The blots shown are representative of at least three independent experiments. C, D Proliferating and senescent (day 7 after γIR) BJ/hTERT (C) and RPE-340/hTERT (D) cells were exposed to the indicated concentrations of the PI3K inhibitors PX-866 and BAY80-6946, the senolytic compound Navitoclax, and the pan-kinase inhibitor staurosporine (3 µM) as a positive control. After 24 h, LDH activity in the cell culture supernatant as a marker for cell death was determined. The data shown are the mean ± SD of at least three independent experiments. Individual data points are represented in the bar charts by small black squares. Significance indicators relate to the corresponding control (proliferating/senescent) treated with DMSO. *p < 0.05, **p < 0.01, ***p < 0.001.

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