1. Proteasomal inhibition suppresses palbociclib‐induced senescence phenotype
Proteasomal inhibition suppresses palbociclib‐induced senescence phenotype ARepresentative maximum‐intensity projections of MCF7 cells treated with the 1 μM palbociclib and/or 7.5 nM bortezomib. Note that 7.5 nM bortezomib inhibits proteasome only partially. Fixed and permeabilized cells were stained with Alexa Fluor 488‐conjugated Ki67 antibody, Alexa Fluor 647‐conjugated phospho‐Histone H2A.X (γH2AX) (pSer139) antibody, and DAPI. All images were acquired with the same magnification, and scale bar is 20 μm.B–DFlow cytometry‐based quantifications of cell size (B), Ki67 levels (C), and pSer139 γH2AX levels (D) from the samples presented in panel (A) (n = 4).ESenescence‐associated beta‐galactosidase activity (blue staining) in MCF7 cells untreated (control) or treated with 7.5 nM bortezomib, 1 μM palbociclib, or a combination of both. Scale bar is 50 μm.FQuantification of the β‐galactosidase activity levels is shown in panel (E) (n = 4).GSchematic model of palbociclib action on cell cycle and cell senescence.Data information: In panels (B–D and F), data are presented as means ± SD; each n represents an individual biological replicate. P‐values were determined by ANOVA and two‐tailed Student's t‐test with Holm–Sidak post hoc test; ns depicts not significant (P > 0.05); **: P < 0.01; ***: P < 0.001.
Teemu P Miettinen et al. EMBO J. 2018;embj
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