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. 2020 Jul 17;11:3606. doi: 10.1038/s41467-020-17384-1

Fig. 1. Nebivolol inhibits mitochondrial respiration in cancer cells.

Fig. 1

a Effect of 1018 FDA-approved drugs on the oligomycin-sensitive respiration (OSR) of HCT116 colon cancer cells. Activators (≥1.4; in blue) and inhibitors (≤0.6; in red) that affected OSR by 40% when compared to control are highlighted. Compounds with no relevant effect (NRE) are shown in gray. b Box plots represent 25th to 75th percentiles with the median value in the middle line, with all data represented from minimal to maximal values indicated with whiskers of the inhibitors (red box) or the compounds with no relevant effect (NRE, black box). c Respiratory profile of HCT116 cells treated (red trace) or not (black trace) for 3 h with nebivolol (1 µM). OCR oxygen consumption rate, OL oligomycin, DNP 2,4-dinitrophenol, ROT rotenone, ANT antimycin A. d Respiratory profile of MDA-MB-231 cells treated (red trace) or not (black trace) for 3 h with nebivolol (1 µM). e Respiratory profile of neuroblastoma SH-SY5Y, lung A549 and ovarian OVCAR8 cells treated (red trace) or not (black trace) for 3 h with nebivolol (1 µM). f Respiratory profile of breast Hs 578T cells treated (red trace) or not (black trace) for 3 h with nebivolol (1 µM). g Respiratory profile of mouse primary neuronal cultures (left panel) and C2C12 myoblast (right panel) treated (red trace) or not (black trace) for 3 h with nebivolol (1 µM). h Basal and OSR of HCT116 cells treated for 3 h with nebivolol (red bar, *p = 0.01 and 0.01), bisoprolol (yellow bar, *p = 0.01 and 0.01), metoprolol (purple bar, *p = 0.04 and 0.03), betaxolol (blue bar, *p = 0.02 and 0.05), acebutolol (green bar, *p = 0.03 and 0.02) (1 µM) or left untreated (black bar). i Respiratory profile of HCT116 cells treated for 3 h (1 µM) with β1-antagonist nebivolol (NEB, red trace and bar; Basal: *p = 0.05; OSR: *p = 0.04; MAX: *p = 0.01), β2-antagonist ICI 118,552 (orange trace and bar), β3-antagonist SR 59230A (gray trace and bar) or left untreated (CRL, black trace and closed bar). j Representative western blots of the expression of β1-adrenergic receptor (ADRB1) in cancer cells (HCT116, MDA-MB-231, A549, SH-SY5Y, and OVCAR8) and normal cells (Hs 578T, primary neurons and C2C12). Tubulin is shown as loading control. Bars indicate the mean ± SEM of three biological replicates. *p < 0.05 and b–e p < 0.05 when compared to CRL by two-sided Student’s t test. See also Supplementary Fig. 1. Source data are provided as a Source Data file.