Fig. 2.

Impact of BH3 mimetics on metabolic activity. (OIS (−DOX), oncogene-induced senescence, 5 days doxycycline withdrawal; proliferation (+DOX): +1 µg/ml doxycycline. D: DMSO; BCL-Xli: BCL-XL inhibitors). (A) Relative metabolic activity after treatment with navitoclax (ATP-based measurement of viable cells; mean ± SD of at least n = 3 biological replicates). (B) DSS (DSS3) of BH3 mimetics, chemotherapeutics, and MEKi in OIS and proliferation (n = 3 biological replicates for each drug, cell line, and mode). (C) Plot of log10 of absolute IC₅₀ values of indicated drugs in OIS (n = 3 biological replicates ± SD). 10 µM (highest concentration applied) was assumed whenever insufficient drug effects precluded IC₅₀ calculation. (D) Mean differential DSS (dDSS) of indicated drugs across three BCL-XLi sensitive PA cell lines (±SD). dDSS: DSS of cells in OIS – DSS of proliferating cells. (E) Relative metabolic activity (ATP-based measurement of viable cells) after treatment with navitoclax in normal human astrocytes NHA TAg compared to PA cell lines in OIS (mean ± SD; at least n = 3). Numbers in dose–response plots are absolute IC₅₀.