ONC201 activates an ISR, decreases cyclin D1 expression, and causes an accumulation of cells in G1 in TNBC cells sensitive to the compounds' antiproliferative.

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ONC201 activates an ISR, decreases cyclin D1 expression, and causes an accumulation of cells in G1 in TNBC cells sensitive to the compounds' antiproliferative effects. ONC201 activates an ISR, decreases cyclin D1 expression, and causes an accumulation of cells in G1 in TNBC cells sensitive to the compounds' antiproliferative effects. A, Western blot analysis of MDA-MB-231 cells for EIF2α phosphorylation, ATF4 expression, and cyclin D1 expression and following treatment with a vehicle control, 5 μmol/L, or 10 μmol/L ONC201 for 72 hours. Densitometry was performed using NIH ImageJ software. The ratio represents the intensity of the phospho-EIF2α band divided by the intensity of the total EIF2α band. B, Quantification of cells in G0–G1, S, and G2 phases of the cell cycle using flow cytometric analysis of PI-stained MDA-MB-231 cells at 24 and 48 hours following treatment with a vehicle control or 10 μmol/L ONC201. ns: P ≥ 0.05; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001. Marie D. Ralff et al. Mol Cancer Ther 2017;16:1290-1298 ©2017 by American Association for Cancer Research